Making Biological Sense of Genetic Studies of Age-Related Macular Degeneration.
AMD
AMD-GWAS
Aging
CREs
Exome sequencing
Functional genomics
GWAS
Genome sequencing
Photoreceptors: RPE
QTLs
eQTL
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
13
4
2021
pubmed:
14
4
2021
medline:
16
4
2021
Statut:
ppublish
Résumé
Age-related macular degeneration (AMD) is a major cause of blindness in older individuals worldwide. The disease is characterized by deposition of drusen between the retinal pigment epithelium (RPE) and Bruch's membrane, RPE atrophy and death of photoreceptors. AMD is a complex disease with multiple genetic and non-genetic risk factors. Genome-wide association studies (GWAS) have identified 52 variants at 34 genetic loci associated with AMD. A majority of the AMD-GWAS variants are present in non-coding region of the genome and could quantitatively impact distinct human traits [called quantitative trait loci (QTLs)] by affecting regulation of gene expression. The integration of different regulatory features, such as open-chromatin regions, histone marks, transcription factor binding sites, with AMD-GWAS can provide meaningful insights into variant's function. However, functional interpretation of variant-gene relationship in AMD is challenging because of inadequate understanding of cell-type specific and context-dependent information in disease-relevant tissues. Here we focus on the role of sequencing-based omic studies in assigning biological meaning to disease-associated variants and genes. We also discuss the methods and model systems that can be utilized to unravel molecular mechanisms of a complex disorder like AMD.
Identifiants
pubmed: 33848003
doi: 10.1007/978-3-030-66014-7_8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
201-219Références
Ferris FL 3rd, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, Sadda SR, Beckman Initiative for Macular Research Classification Classification (2013) Clinical classification of age-related macular degeneration. Ophthalmology 120(4):844–851. https://doi.org/10.1016/j.ophtha.2012.10.036
doi: 10.1016/j.ophtha.2012.10.036
pubmed: 23332590
pmcid: 23332590
Ambati J, Fowler BJ (2012) Mechanisms of age-related macular degeneration. Neuron 75(1):26–39. https://doi.org/10.1016/j.neuron.2012.06.018
doi: 10.1016/j.neuron.2012.06.018
pubmed: 22794258
pmcid: 3404137
Ratnapriya R, Chew EY (2013) Age-related macular degeneration-clinical review and genetics update. Clin Genet 84(2):160–166. https://doi.org/10.1111/cge.12206
doi: 10.1111/cge.12206
pubmed: 23713713
pmcid: 3732788
Yankner BA, Lu T, Loerch P (2008) The aging brain. Annu Rev Pathol 3:41–66
doi: 10.1146/annurev.pathmechdis.2.010506.092044
Swaroop A, Chew EY, Rickman CB, Abecasis GR (2009) Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration. Annu Rev Genomics Hum Genet 10:19–43. https://doi.org/10.1146/annurev.genom.9.081307.164350
doi: 10.1146/annurev.genom.9.081307.164350
pubmed: 19405847
pmcid: 3469316
Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE, Rando TA, Richardson A, Schadt EE, Wyss-Coray T, Sierra F (2014) Geroscience: linking aging to chronic disease. Cell 159(4):709–713. https://doi.org/10.1016/j.cell.2014.10.039
doi: 10.1016/j.cell.2014.10.039
pubmed: 25417146
pmcid: 4852871
Luu J, Palczewski K (2018) Human aging and disease: lessons from age-related macular degeneration. Proc Natl Acad Sci U S A 115(12):2866–2872. https://doi.org/10.1073/pnas.1721033115
doi: 10.1073/pnas.1721033115
pubmed: 29483257
pmcid: 5866596
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217. https://doi.org/10.1016/j.cell.2013.05.039
doi: 10.1016/j.cell.2013.05.039
pubmed: 23746838
pmcid: 3836174
Booth LN, Brunet A (2016) The aging epigenome. Mol Cell 62(5):728–744. https://doi.org/10.1016/j.molcel.2016.05.013
doi: 10.1016/j.molcel.2016.05.013
pubmed: 27259204
pmcid: 4917370
Lodato MA, Rodin RE, Bohrson CL, Coulter ME, Barton AR, Kwon M, Sherman MA, Vitzthum CM, Luquette LJ, Yandava CN, Yang P, Chittenden TW, Hatem NE, Ryu SC, Woodworth MB, Park PJ, Walsh CA (2018) Aging and neurodegeneration are associated with increased mutations in single human neurons. Science 359(6375):555–559. https://doi.org/10.1126/science.aao4426
doi: 10.1126/science.aao4426
Seddon JM, George S, Rosner B, Klein ML (2006) CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration. Hum Hered 61(3):157–165
doi: 10.1159/000094141
SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD (2007) The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS report no. 22. Arch Ophthalmol 125(9):1225–1232
doi: 10.1001/archopht.125.9.1225
Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl):245–254
doi: 10.1038/ng1089
Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury JF, Bueno R, Sugarbaker DJ, Yeh R-F, Wiencke JK, Kelsey KT (2009) Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 5:e1000602. https://doi.org/10.1371/journal.pgen.1000602
doi: 10.1371/journal.pgen.1000602
pubmed: 19680444
pmcid: 2718614
Heiba IM, Elston RC, Klein BE, Klein R (1994) Sibling correlations and segregation analysis of age-related maculopathy: the Beaver Dam Eye Study. Genet Epidemiol 11(1):51–67
doi: 10.1002/gepi.1370110106
Klaver CC, Kliffen M, van Duijn CM, Hofman A, Cruts M, Grobbee DE, van Broeckhoven C, de Jong PT (1998) Genetic association of apolipoprotein E with age-related macular degeneration. Am J Hum Genet 63(1):200–206. https://doi.org/10.1086/301901
doi: 10.1086/301901
pubmed: 9634502
pmcid: 1377225
Allikmets R, Shroyer NF, Singh N, Seddon JM, Lewis RA, Bernstein PS, Peiffer A, Zabriskie NA, Li Y, Hutchinson A, Dean M, Lupski JR, Leppert M (1997) Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science 277(5333):1805–1807
doi: 10.1126/science.277.5333.1805
Swaroop A, Branham KE, Chen W, Abecasis G (2007) Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits. Hum Mol Genetics. https://doi.org/10.1093/hmg/ddm212
Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308(5720):385–389. https://doi.org/10.1126/science.1109557
doi: 10.1126/science.1109557
pubmed: 1512523
pmcid: 1512523
Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308(5720):421–424. https://doi.org/10.1126/science.1110189
doi: 10.1126/science.1110189
Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan SY, Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA, Pericak-Vance MA (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308(5720):419–421. https://doi.org/10.1126/science.1110359
doi: 10.1126/science.1110359
Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A 102(20):7227–7232. https://doi.org/10.1073/pnas.0501536102
doi: 10.1073/pnas.0501536102
pubmed: 15870199
pmcid: 1088171
Zareparsi S, Branham KE, Li M, Shah S, Klein RJ, Ott J, Hoh J, Abecasis GR, Swaroop A (2005) Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration. Am J Hum Genet 77(1):149–153. https://doi.org/10.1086/431426
doi: 10.1086/431426
pubmed: 15895326
pmcid: 1226187
Li M, Atmaca-Sonmez P, Othman M, Branham KE, Khanna R, Wade MS, Li Y, Liang L, Zareparsi S, Swaroop A, Abecasis GR (2006) CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration. Nat Genet 38(9):1049–1054. https://doi.org/10.1038/ng1871
doi: 10.1038/ng1871
pubmed: 16936733
pmcid: 1941700
Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J, Bergeron J, Barile GR, Smith RT, Hageman GS, Dean M, Allikmets R, Group AMDGCS (2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet 38(4):458–462. https://doi.org/10.1038/ng1750
doi: 10.1038/ng1750
pubmed: 16518403
pmcid: 2921703
Maller J, George S, Purcell S, Fagerness J, Altshuler D, Daly MJ, Seddon JM (2006) Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nat Genet 38(9):1055–1059. https://doi.org/10.1038/ng1873
doi: 10.1038/ng1873
pubmed: 16936732
Kanda A, Chen W, Othman M, Branham KE, Brooks M, Khanna R, He S, Lyons R, Abecasis GR, Swaroop A (2007) A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration. Proc Natl Acad Sci U S A 104(41):16227–16232. https://doi.org/10.1073/pnas.0703933104
doi: 10.1073/pnas.0703933104
pubmed: 17884985
pmcid: 1987388
Fritsche LG, Loenhardt T, Janssen A, Fisher SA, Rivera A, Keilhauer CN, Weber BH (2008) Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nat Genet 40(7):892–896
doi: 10.1038/ng.170
Chen W, Stambolian D, Edwards AO, Branham KE, Othman M, Jakobsdottir J, Tosakulwong N, Pericak-Vance MA, Campochiaro PA, Klein ML, Tan PL, Conley YP, Kanda A, Kopplin L, Li Y, Augustaitis KJ, Karoukis AJ, Scott WK, Agarwal A, Kovach JL, Schwartz SG, Postel EA, Brooks M, Baratz KH, Brown WL, Brucker AJ, Orlin A, Brown G, Ho A, Regillo C, Donoso L, Tian L, Kaderli B, Hadley D, Hagstrom SA, Peachey NS, Klein R, Klein BE, Gotoh N, Yamashiro K, Ferris Iii F, Fagerness JA, Reynolds R, Farrer LA, Kim IK, Miller JW, Corton M, Carracedo A, Sanchez-Salorio M, Pugh EW, Doheny KF, Brion M, Deangelis MM, Weeks DE, Zack DJ, Chew EY, Heckenlively JR, Yoshimura N, Iyengar SK, Francis PJ, Katsanis N, Seddon JM, Haines JL, Gorin MB, Abecasis GR, Swaroop A (2010) Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci U S A 107(16):7401–7406. https://doi.org/10.1073/pnas.0912702107
doi: 10.1073/pnas.0912702107
pubmed: 20385819
pmcid: 2867722
Neale BM, Fagerness J, Reynolds R, Sobrin L, Parker M, Raychaudhuri S, Tan PL, Oh EC, Merriam JE, Souied E, Bernstein PS, Li B, Frederick JM, Zhang K, Brantley MA Jr, Lee AY, Zack DJ, Campochiaro B, Campochiaro P, Ripke S, Smith RT, Barile GR, Katsanis N, Allikmets R, Daly MJ, Seddon JM (2010) Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proc Natl Acad Sci U S A 107(16):7395–7400. https://doi.org/10.1073/pnas.0912019107
doi: 10.1073/pnas.0912019107
pubmed: 20385826
pmcid: 2867697
Fritsche LG, Chen W, Schu M, Yaspan BL, Yu Y, Thorleifsson G, Zack DJ, Arakawa S, Cipriani V, Ripke S, Igo RP Jr, Buitendijk GH, Sim X, Weeks DE, Guymer RH, Merriam JE, Francis PJ, Hannum G, Agarwal A, Armbrecht AM, Audo I, Aung T, Barile GR, Benchaboune M, Bird AC, Bishop PN, Branham KE, Brooks M, Brucker AJ, Cade WH, Cain MS, Campochiaro PA, Chan CC, Cheng CY, Chew EY, Chin KA, Chowers I, Clayton DG, Cojocaru R, Conley YP, Cornes BK, Daly MJ, Dhillon B, Edwards AO, Evangelou E, Fagerness J, Ferreyra HA, Friedman JS, Geirsdottir A, George RJ, Gieger C, Gupta N, Hagstrom SA, Harding SP, Haritoglou C, Heckenlively JR, Holz FG, Hughes G, Ioannidis JP, Ishibashi T, Joseph P, Jun G, Kamatani Y, Katsanis N, Keilhauer CN, Khan JC, Kim IK, Kiyohara Y, Klein BE, Klein R, Kovach JL, Kozak I, Lee CJ, Lee KE, Lichtner P, Lotery AJ, Meitinger T, Mitchell P, Mohand-Said S, Moore AT, Morgan DJ, Morrison MA, Myers CE, Naj AC, Nakamura Y, Okada Y, Orlin A, Ortube MC, Othman MI, Pappas C, Park KH, Pauer GJ, Peachey NS, Poch O, Priya RR, Reynolds R, Richardson AJ, Ripp R, Rudolph G, Ryu E, Sahel JA, Schaumberg DA, Scholl HP, Schwartz SG, Scott WK, Shahid H, Sigurdsson H, Silvestri G, Sivakumaran TA, Smith RT, Sobrin L, Souied EH, Stambolian DE, Stefansson H, Sturgill-Short GM, Takahashi A, Tosakulwong N, Truitt BJ, Tsironi EE, Uitterlinden AG, van Duijn CM, Vijaya L, Vingerling JR, Vithana EN, Webster AR, Wichmann HE, Winkler TW, Wong TY, Wright AF, Zelenika D, Zhang M, Zhao L, Zhang K, Klein ML, Hageman GS, Lathrop GM, Stefansson K, Allikmets R, Baird PN, Gorin MB, Wang JJ, Klaver CC, Seddon JM, Pericak-Vance MA, Iyengar SK, Yates JR, Swaroop A, Weber BH, Kubo M, Deangelis MM, Leveillard T, Thorsteinsdottir U, Haines JL, Farrer LA, Heid IM, Abecasis GR, Consortium AMDG (2013) Seven new loci associated with age-related macular degeneration. Nat Genet 45(4):433–439. https://doi.org/10.1038/ng.2578
doi: 10.1038/ng.2578
pubmed: 23455636
Beck T, Hastings RK, Gollapudi S, Free RC, Brookes AJ (2014) GWAS central: a comprehensive resource for the comparison and interrogation of genome-wide association studies. Eur J Hum Genet 22(7):949–952. https://doi.org/10.1038/ejhg.2013.274
doi: 10.1038/ejhg.2013.274
pubmed: 24301061
1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, GA MV, Abecasis GR (2015) A global reference for human genetic variation. Nature 526(7571):68–74. https://doi.org/10.1038/nature15393
doi: 10.1038/nature15393
McCarthy S, Das S, Kretzschmar W, Delaneau O, Wood AR, Teumer A, Kang HM, Fuchsberger C, Danecek P, Sharp K, Luo Y, Sidore C, Kwong A, Timpson N, Koskinen S, Vrieze S, Scott LJ, Zhang H, Mahajan A, Veldink J, Peters U, Pato C, van Duijn CM, Gillies CE, Gandin I, Mezzavilla M, Gilly A, Cocca M, Traglia M, Angius A, Barrett JC, Boomsma D, Branham K, Breen G, Brummett CM, Busonero F, Campbell H, Chan A, Chen S, Chew E, Collins FS, Corbin LJ, Smith GD, Dedoussis G, Dorr M, Farmaki AE, Ferrucci L, Forer L, Fraser RM, Gabriel S, Levy S, Groop L, Harrison T, Hattersley A, Holmen OL, Hveem K, Kretzler M, Lee JC, McGue M, Meitinger T, Melzer D, Min JL, Mohlke KL, Vincent JB, Nauck M, Nickerson D, Palotie A, Pato M, Pirastu N, McInnis M, Richards JB, Sala C, Salomaa V, Schlessinger D, Schoenherr S, Slagboom PE, Small K, Spector T, Stambolian D, Tuke M, Tuomilehto J, Van den Berg LH, Van Rheenen W, Volker U, Wijmenga C, Toniolo D, Zeggini E, Gasparini P, Sampson MG, Wilson JF, Frayling T, de Bakker PI, Swertz MA, McCarroll S, Kooperberg C, Dekker A, Altshuler D, Willer C, Iacono W, Ripatti S, Soranzo N, Walter K, Swaroop A, Cucca F, Anderson CA, Myers RM, Boehnke M, McCarthy MI, Durbin R, Haplotype Reference C (2016) A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet 48(10):1279–1283. https://doi.org/10.1038/ng.3643
doi: 10.1038/ng.3643
pubmed: 27548312
pmcid: 5388176
Fritsche LG, Igl W, Bailey JN, Grassmann F, Sengupta S, Bragg-Gresham JL, Burdon KP, Hebbring SJ, Wen C, Gorski M, Kim IK, Cho D, Zack D, Souied E, Scholl HP, Bala E, Lee KE, Hunter DJ, Sardell RJ, Mitchell P, Merriam JE, Cipriani V, Hoffman JD, Schick T, Lechanteur YT, Guymer RH, Johnson MP, Jiang Y, Stanton CM, Buitendijk GH, Zhan X, Kwong AM, Boleda A, Brooks M, Gieser L, Ratnapriya R, Branham KE, Foerster JR, Heckenlively JR, Othman MI, Vote BJ, Liang HH, Souzeau E, McAllister IL, Isaacs T, Hall J, Lake S, Mackey DA, Constable IJ, Craig JE, Kitchner TE, Yang Z, Su Z, Luo H, Chen D, Ouyang H, Flagg K, Lin D, Mao G, Ferreyra H, Stark K, von Strachwitz CN, Wolf A, Brandl C, Rudolph G, Olden M, Morrison MA, Morgan DJ, Schu M, Ahn J, Silvestri G, Tsironi EE, Park KH, Farrer LA, Orlin A, Brucker A, Li M, Curcio CA, Mohand-Said S, Sahel JA, Audo I, Benchaboune M, Cree AJ, Rennie CA, Goverdhan SV, Grunin M, Hagbi-Levi S, Campochiaro P, Katsanis N, Holz FG, Blond F, Blanche H, Deleuze JF, Igo RP Jr, Truitt B, Peachey NS, Meuer SM, Myers CE, Moore EL, Klein R, Hauser MA, Postel EA, Courtenay MD, Schwartz SG, Kovach JL, Scott WK, Liew G, Tan AG, Gopinath B, Merriam JC, Smith RT, Khan JC, Shahid H, Moore AT, McGrath JA, Laux R, Brantley MA Jr, Agarwal A, Ersoy L, Caramoy A, Langmann T, Saksens NT, de Jong EK, Hoyng CB, Cain MS, Richardson AJ, Martin TM, Blangero J, Weeks DE, Dhillon B, van Duijn CM, Doheny KF, Romm J, Klaver CC, Hayward C, Gorin MB, Klein ML, Baird PN, den Hollander AI, Fauser S, Yates JR, Allikmets R, Wang JJ, Schaumberg DA, Klein BE, Hagstrom SA, Chowers I, Lotery AJ, Leveillard T, Zhang K, Brilliant MH, Hewitt AW, Swaroop A, Chew EY, Pericak-Vance MA, DeAngelis M, Stambolian D, Haines JL, Iyengar SK, Weber BH, Abecasis GR, Heid IM (2016) A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet 48(2):134–143. https://doi.org/10.1038/ng.3448
doi: 10.1038/ng.3448
pubmed: 26691988
Seddon JM, Yu Y, Miller EC, Reynolds R, Tan PL, Gowrisankar S, Goldstein JI, Triebwasser M, Anderson HE, Zerbib J, Kavanagh D, Souied E, Katsanis N, Daly MJ, Atkinson JP, Raychaudhuri S (2013) Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. Nat Genet. https://doi.org/10.1038/ng.2741
Zhan X, Larson DE, Wang C, Koboldt DC, Sergeev YV, Fulton RS, Fulton LL, Fronick CC, Branham KE, Bragg-Gresham J, Jun G, Hu Y, Kang HM, Liu D, Othman M, Brooks M, Ratnapriya R, Boleda A, Grassmann F, von Strachwitz C, Olson LM, Buitendijk GH, Hofman A, van Duijn CM, Cipriani V, Moore AT, Shahid H, Jiang Y, Conley YP, Morgan DJ, Kim IK, Johnson MP, Cantsilieris S, Richardson AJ, Guymer RH, Luo H, Ouyang H, Licht C, Pluthero FG, Zhang MM, Zhang K, Baird PN, Blangero J, Klein ML, Farrer LA, DeAngelis MM, Weeks DE, Gorin MB, Yates JR, Klaver CC, Pericak-Vance MA, Haines JL, Weber BH, Wilson RK, Heckenlively JR, Chew EY, Stambolian D, Mardis ER, Swaroop A, Abecasis GR (2013) Identification of a rare coding variant in complement 3 associated with age-related macular degeneration. Nat Genet 45(11):1375–1379. https://doi.org/10.1038/ng.2758
doi: 10.1038/ng.2758
pubmed: 24036949
pmcid: 3812337
Yu Y, Triebwasser MP, Wong EK, Schramm EC, Thomas B, Reynolds R, Mardis ER, Atkinson JP, Daly M, Raychaudhuri S, Kavanagh D, Seddon JM (2014) Whole-exome sequencing identifies rare, functional CFH variants in families with macular degeneration. Hum Mol Genet 23(19):5283–5293. https://doi.org/10.1093/hmg/ddu226
doi: 10.1093/hmg/ddu226
pubmed: 24847005
pmcid: 4159152
Pietraszkiewicz A, van Asten F, Kwong A, Ratnapriya R, Abecasis G, Swaroop A, Chew EY (2018) Association of rare predicted loss-of-function variants in cellular pathways with sub-phenotypes in age-related macular degeneration. Ophthalmology 125(3):398–406. https://doi.org/10.1016/j.ophtha.2017.10.027
doi: 10.1016/j.ophtha.2017.10.027
pubmed: 29224928
Ratnapriya R, Acar IE, Geerlings MJ, Branham K, Kwong A, Saksens NTM, Pauper M, Corominas J, Kwicklis M, Zipprer D, Starostik MR, Othman M, Yashar B, Abecasis GR, Chew EY, Ferrington DA, Hoyng CB, Swaroop A, Hollander AI (2020) Family-based exome sequencing identifies rare coding variants in age-related macular degeneration. Hum Mol Genet. https://doi.org/10.1093/hmg/ddaa057
Duvvari MR, van de Ven JP, Geerlings MJ, Saksens NT, Bakker B, Henkes A, Neveling K, del Rosario M, Westra D, van den Heuvel LP, Schick T, Fauser S, Boon CJ, Hoyng CB, de Jong EK, den Hollander AI (2016) Whole exome sequencing in patients with the cuticular drusen subtype of age-related macular degeneration. PLoS One 11(3):e0152047. https://doi.org/10.1371/journal.pone.0152047
doi: 10.1371/journal.pone.0152047
pubmed: 27007659
pmcid: 4805164
Beryozkin A, Shevah E, Kimchi A, Mizrahi-Meissonnier L, Khateb S, Ratnapriya R, Lazar CH, Blumenfeld A, Ben-Yosef T, Hemo Y, Pe'er J, Averbuch E, Sagi M, Boleda A, Gieser L, Zlotogorski A, Falik-Zaccai T, Alimi-Kasem O, Jacobson SG, Chowers I, Swaroop A, Banin E, Sharon D (2015) Whole exome sequencing reveals mutations in known retinal disease genes in 33 out of 68 Israeli families with inherited retinopathies. Sci Rep 5:13187. https://doi.org/10.1038/srep13187
doi: 10.1038/srep13187
pubmed: 26306921
pmcid: 4549705
Fritsche LG, Fariss RN, Stambolian D, Abecasis GR, Curcio CA, Swaroop A (2014) Age-related macular degeneration: genetics and biology coming together. Annu Rev Genomics Hum Genet 15:151–171. https://doi.org/10.1146/annurev-genom-090413-025610
doi: 10.1146/annurev-genom-090413-025610
pubmed: 24773320
pmcid: 4217162
Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296(5576):2225–2229. https://doi.org/10.1126/science.1069424
doi: 10.1126/science.1069424
pubmed: 12029063
Consortium EP, Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, Epstein CB, Frietze S, Harrow J, Kaul R, Khatun J, Lajoie BR, Landt SG, Lee BK, Pauli F, Rosenbloom KR, Sabo P, Safi A, Sanyal A, Shoresh N, Simon JM, Song L, Trinklein ND, Altshuler RC, Birney E, Brown JB, Cheng C, Djebali S, Dong X, Dunham I, Ernst J, Furey TS, Gerstein M, Giardine B, Greven M, Hardison RC, Harris RS, Herrero J, Hoffman MM, Iyer S, Kelllis M, Khatun J, Kheradpour P, Kundaje A, Lassman T, Li Q, Lin X, Marinov GK, Merkel A, Mortazavi A, Parker SC, Reddy TE, Rozowsky J, Schlesinger F, Thurman RE, Wang J, Ward LD, Whitfield TW, Wilder SP, Wu W, Xi HS, Yip KY, Zhuang J, Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M, Pazin MJ, Lowdon RF, Dillon LA, Adams LB, Kelly CJ, Zhang J, Wexler JR, Green ED, Good PJ, Feingold EA, Bernstein BE, Birney E, Crawford GE, Dekker J, Elinitski L, Farnham PJ, Gerstein M, Giddings MC, Gingeras TR, Green ED, Guigo R, Hardison RC, Hubbard TJ, Kellis M, Kent WJ, Lieb JD, Margulies EH, Myers RM, Snyder M, Starnatoyannopoulos JA, Tennebaum SA, Weng Z, White KP, Wold B, Khatun J, Yu Y, Wrobel J, Risk BA, Gunawardena HP, Kuiper HC, Maier CW, Xie L, Chen X, Giddings MC, Bernstein BE, Epstein CB, Shoresh N, Ernst J, Kheradpour P, Mikkelsen TS, Gillespie S, Goren A, Ram O, Zhang X, Wang L, Issner R, Coyne MJ, Durham T, Ku M, Truong T, Ward LD, Altshuler RC, Eaton ML, Kellis M, Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Roder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Batut P, Bell I, Bell K, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena HP, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Li G, Luo OJ, Park E, Preall JB, Presaud K, Ribeca P, Risk BA, Robyr D, Ruan X, Sammeth M, Sandu KS, Schaeffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Hayashizaki Y, Harrow J, Gerstein M, Hubbard TJ, Reymond A, Antonarakis SE, Hannon GJ, Giddings MC, Ruan Y, Wold B, Carninci P, Guigo R, Gingeras TR, Rosenbloom KR, Sloan CA, Learned K, Malladi VS, Wong MC, Barber GP, Cline MS, Dreszer TR, Heitner SG, Karolchik D, Kent WJ, Kirkup VM, Meyer LR, Long JC, Maddren M, Raney BJ, Furey TS, Song L, Grasfeder LL, Giresi PG, Lee BK, Battenhouse A, Sheffield NC, Simon JM, Showers KA, Safi A, London D, Bhinge AA, Shestak C, Schaner MR, Kim SK, Zhang ZZ, Mieczkowski PA, Mieczkowska JO, Liu Z, McDaniell RM, Ni Y, Rashid NU, Kim MJ, Adar S, Zhang Z, Wang T, Winter D, Keefe D, Birney E, Iyer VR, Lieb JD, Crawford GE, Li G, Sandhu KS, Zheng M, Wang P, Luo OJ, Shahab A, Fullwood MJ, Ruan X, Ruan Y, Myers RM, Pauli F, Williams BA, Gertz J, Marinov GK, Reddy TE, Vielmetter J, Partridge EC, Trout D, Varley KE, Gasper C, Bansal A, Pepke S, Jain P, Amrhein H, Bowling KM, Anaya M, Cross MK, King B, Muratet MA, Antoshechkin I, Newberry KM, McCue K, Nesmith AS, Fisher-Aylor KI, Pusey B, DeSalvo G, Parker SL, Balasubramanian S, Davis NS, Meadows SK, Eggleston T, Gunter C, Newberry JS, Levy SE, Absher DM, Mortazavi A, Wong WH, Wold B, Blow MJ, Visel A, Pennachio LA, Elnitski L, Margulies EH, Parker SC, Petrykowska HM, Abyzov A, Aken B, Barrell D, Barson G, Berry A, Bignell A, Boychenko V, Bussotti G, Chrast J, Davidson C, Derrien T, Despacio-Reyes G, Diekhans M, Ezkurdia I, Frankish A, Gilbert J, Gonzalez JM, Griffiths E, Harte R, Hendrix DA, Howald C, Hunt T, Jungreis I, Kay M, Khurana E, Kokocinski F, Leng J, Lin MF, Loveland J, Lu Z, Manthravadi D, Mariotti M, Mudge J, Mukherjee G, Notredame C, Pei B, Rodriguez JM, Saunders G, Sboner A, Searle S, Sisu C, Snow C, Steward C, Tanzer A, Tapanari E, Tress ML, van Baren MJ, Walters N, Washieti S, Wilming L, Zadissa A, Zhengdong Z, Brent M, Haussler D, Kellis M, Valencia A, Gerstein M, Raymond A, Guigo R, Harrow J, Hubbard TJ, Landt SG, Frietze S, Abyzov A, Addleman N, Alexander RP, Auerbach RK, Balasubramanian S, Bettinger K, Bhardwaj N, Boyle AP, Cao AR, Cayting P, Charos A, Cheng Y, Cheng C, Eastman C, Euskirchen G, Fleming JD, Grubert F, Habegger L, Hariharan M, Harmanci A, Iyenger S, Jin VX, Karczewski KJ, Kasowski M, Lacroute P, Lam H, Larnarre-Vincent N, Leng J, Lian J, Lindahl-Allen M, Min R, Miotto B, Monahan H, Moqtaderi Z, Mu XJ, O’Geen H, Ouyang Z, Patacsil D, Pei B, Raha D, Ramirez L, Reed B, Rozowsky J, Sboner A, Shi M, Sisu C, Slifer T, Witt H, Wu L, Xu X, Yan KK, Yang X, Yip KY, Zhang Z, Struhl K, Weissman SM, Gerstein M, Farnham PJ, Snyder M, Tenebaum SA, Penalva LO, Doyle F, Karmakar S, Landt SG, Bhanvadia RR, Choudhury A, Domanus M, Ma L, Moran J, Patacsil D, Slifer T, Victorsen A, Yang X, Snyder M, White KP, Auer T, Centarin L, Eichenlaub M, Gruhl F, Heerman S, Hoeckendorf B, Inoue D, Kellner T, Kirchmaier S, Mueller C, Reinhardt R, Schertel L, Schneider S, Sinn R, Wittbrodt B, Wittbrodt J, Weng Z, Whitfield TW, Wang J, Collins PJ, Aldred SF, Trinklein ND, Partridge EC, Myers RM, Dekker J, Jain G, Lajoie BR, Sanyal A, Balasundaram G, Bates DL, Byron R, Canfield TK, Diegel MJ, Dunn D, Ebersol AK, Ebersol AK, Frum T, Garg K, Gist E, Hansen RS, Boatman L, Haugen E, Humbert R, Jain G, Johnson AK, Johnson EM, Kutyavin TM, Lajoie BR, Lee K, Lotakis D, Maurano MT, Neph SJ, Neri FV, Nguyen ED, Qu H, Reynolds AP, Roach V, Rynes E, Sabo P, Sanchez ME, Sandstrom RS, Sanyal A, Shafer AO, Stergachis AB, Thomas S, Thurman RE, Vernot B, Vierstra J, Vong S, Wang H, Weaver MA, Yan Y, Zhang M, Akey JA, Bender M, Dorschner MO, Groudine M, MacCoss MJ, Navas P, Stamatoyannopoulos G, Kaul R, Dekker J, Stamatoyannopoulos JA, Dunham I, Beal K, Brazma A, Flicek P, Herrero J, Johnson N, Keefe D, Lukk M, Luscombe NM, Sobral D, Vaquerizas JM, Wilder SP, Batzoglou S, Sidow A, Hussami N, Kyriazopoulou-Panagiotopoulou S, Libbrecht MW, Schaub MA, Kundaje A, Hardison RC, Miller W, Giardine B, Harris RS, Wu W, Bickel PJ, Banfai B, Boley NP, Brown JB, Huang H, Li Q, Li JJ, Noble WS, Bilmes JA, Buske OJ, Hoffman MM, Sahu AO, Kharchenko PV, Park PJ, Baker D, Taylor J, Weng Z, Iyer S, Dong X, Greven M, Lin X, Wang J, Xi HS, Zhuang J, Gerstein M, Alexander RP, Balasubramanian S, Cheng C, Harmanci A, Lochovsky L, Min R, Mu XJ, Rozowsky J, Yan KK, Yip KY, Birney E (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414):57–74. https://doi.org/10.1038/nature11247
doi: 10.1038/nature11247
Cookson W, Liang L, Abecasis G, Moffatt M, Lathrop M (2009) Mapping complex disease traits with global gene expression. Nat Rev Genet 10(3):184–194. https://doi.org/10.1038/nrg2537
doi: 10.1038/nrg2537
pubmed: 4550035
pmcid: 4550035
Takata A, Matsumoto N, Kato T (2017) Genome-wide identification of splicing QTLs in the human brain and their enrichment among schizophrenia-associated loci. Nat Commun 8:14519. https://doi.org/10.1038/ncomms14519
doi: 10.1038/ncomms14519
pubmed: 28240266
pmcid: 5333373
Degner JF, Pai AA, Pique-Regi R, Veyrieras JB, Gaffney DJ, Pickrell JK, De Leon S, Michelini K, Lewellen N, Crawford GE, Stephens M, Gilad Y, Pritchard JK (2012) DNase I sensitivity QTLs are a major determinant of human expression variation. Nature 482(7385):390–394. https://doi.org/10.1038/nature10808
doi: 10.1038/nature10808
pubmed: 22307276
pmcid: 3501342
Ciuculete DM, Bostrom AE, Voisin S, Philipps H, Titova OE, Bandstein M, Nikontovic L, Williams MJ, Mwinyi J, Schioth HB (2017) A methylome-wide mQTL analysis reveals associations of methylation sites with GAD1 and HDAC3 SNPs and a general psychiatric risk score. Transl Psychiatry 7(1):e1002. https://doi.org/10.1038/tp.2016.275
doi: 10.1038/tp.2016.275
pubmed: 28094813
pmcid: 5545735
Tehranchi AK, Myrthil M, Martin T, Hie BL, Golan D, Fraser HB (2016) Pooled ChIP-Seq links variation in transcription factor binding to complex disease risk. Cell 165(3):730–741. https://doi.org/10.1016/j.cell.2016.03.041
doi: 10.1016/j.cell.2016.03.041
pubmed: 27087447
pmcid: 27087447
Battle A, Khan Z, Wang SH, Mitrano A, Ford MJ, Pritchard JK, Gilad Y (2015) Genomic variation. Impact of regulatory variation from RNA to protein. Science 347(6222):664–667. https://doi.org/10.1126/science.1260793
doi: 10.1126/science.1260793
pubmed: 25657249
Chabi B, Ljubicic V, Menzies KJ, Huang JH, Saleem A, Hood DA (2008) Mitochondrial function and apoptotic susceptibility in aging skeletal muscle. Aging Cell 7(1):2–12
doi: 10.1111/j.1474-9726.2007.00347.x
Castel SE, Cervera A, Mohammadi P, Aguet F, Reverter F, Wolman A, Guigo R, Iossifov I, Vasileva A, Lappalainen T (2018) Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk. Nat Genet 50(9):1327–1334. https://doi.org/10.1038/s41588-018-0192-y
doi: 10.1038/s41588-018-0192-y
pubmed: 30127527
pmcid: 6119105
Zelinger L, Swaroop A (2018) RNA biology in retinal development and disease. Trends Genet 34(5):341–351. https://doi.org/10.1016/j.tig.2018.01.002
doi: 10.1016/j.tig.2018.01.002
pubmed: 29395379
pmcid: 5910263
Kim JW, Yang HJ, Brooks MJ, Zelinger L, Karakulah G, Gotoh N, Boleda A, Gieser L, Giuste F, Whitaker DT, Walton A, Villasmil R, Barb JJ, Munson PJ, Kaya KD, Chaitankar V, Cogliati T, Swaroop A (2016) NRL-regulated transcriptome dynamics of developing rod photoreceptors. Cell Rep 17(9):2460–2473. https://doi.org/10.1016/j.celrep.2016.10.074
doi: 10.1016/j.celrep.2016.10.074
pubmed: 27880916
pmcid: 5131731
Liu MM, Zack DJ (2013) Alternative splicing and retinal degeneration. Clin Genet 84(2):142–149. https://doi.org/10.1111/cge.12181
doi: 10.1111/cge.12181
pubmed: 23647439
pmcid: 4147722
Kole C, Berdugo N, Da Silva C, Ait-Ali N, Millet-Puel G, Pagan D, Blond F, Poidevin L, Ripp R, Fontaine V, Wincker P, Zack DJ, Sahel JA, Poch O, Leveillard T (2016) Identification of an alternative splicing product of the Otx2 gene expressed in the neural retina and retinal pigmented epithelial cells. PLoS One 11(3):e0150758. https://doi.org/10.1371/journal.pone.0150758
doi: 10.1371/journal.pone.0150758
pubmed: 26985665
pmcid: 4795653
Pickrell JK, Marioni JC, Pai AA, Degner JF, Engelhardt BE, Nkadori E, Veyrieras JB, Stephens M, Gilad Y, Pritchard JK (2010) Understanding mechanisms underlying human gene expression variation with RNA sequencing. Nature 464(7289):768–772. https://doi.org/10.1038/nature08872
doi: 10.1038/nature08872
pubmed: 20220758
pmcid: 3089435
Birnbaum RY, Clowney EJ, Agamy O, Kim MJ, Zhao J, Yamanaka T, Pappalardo Z, Clarke SL, Wenger AM, Nguyen L, Gurrieri F, Everman DB, Schwartz CE, Birk OS, Bejerano G, Lomvardas S, Ahituv N (2012) Coding exons function as tissue-specific enhancers of nearby genes. Genome Res 22(6):1059–1068. https://doi.org/10.1101/gr.133546.111
doi: 10.1101/gr.133546.111
pubmed: 22442009
pmcid: 3371700
Berry-Kravis EM, Lindemann L, Jonch AE, Apostol G, Bear MF, Carpenter RL, Crawley JN, Curie A, Des Portes V, Hossain F, Gasparini F, Gomez-Mancilla B, Hessl D, Loth E, Scharf SH, Wang PP, Von Raison F, Hagerman R, Spooren W, Jacquemont S (2018) Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome. Nat Rev Drug Discov 17(4):280–299. https://doi.org/10.1038/nrd.2017.221
doi: 10.1038/nrd.2017.221
pubmed: 29217836
Boyle AP, Davis S, Shulha HP, Meltzer P, Margulies EH, Weng Z, Furey TS, Crawford GE (2008) High-resolution mapping and characterization of open chromatin across the genome. Cell 132(2):311–322. https://doi.org/10.1016/j.cell.2007.12.014
doi: 10.1016/j.cell.2007.12.014
pubmed: 18243105
pmcid: 2669738
McDaniell R, Lee BK, Song L, Liu Z, Boyle AP, Erdos MR, Scott LJ, Morken MA, Kucera KS, Battenhouse A, Keefe D, Collins FS, Willard HF, Lieb JD, Furey TS, Crawford GE, Iyer VR, Birney E (2010) Heritable individual-specific and allele-specific chromatin signatures in humans. Science 328(5975):235–239. https://doi.org/10.1126/science.1184655
doi: 10.1126/science.1184655
pubmed: 20299549
pmcid: 2929018
Buskin A, Zhu L, Chichagova V, Basu B, Mozaffari-Jovin S, Dolan D, Droop A, Collin J, Bronstein R, Mehrotra S, Farkas M, Hilgen G, White K, Pan KT, Treumann A, Hallam D, Bialas K, Chung G, Mellough C, Ding Y, Krasnogor N, Przyborski S, Zwolinski S, Al-Aama J, Alharthi S, Xu Y, Wheway G, Szymanska K, McKibbin M, Inglehearn CF, Elliott DJ, Lindsay S, Ali RR, Steel DH, Armstrong L, Sernagor E, Urlaub H, Pierce E, Luhrmann R, Grellscheid SN, Johnson CA, Lako M (2018) Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa. Nat Commun 9(1):4234. https://doi.org/10.1038/s41467-018-06448-y
doi: 10.1038/s41467-018-06448-y
pubmed: 30315276
pmcid: 6185938
Schaub MA, Boyle AP, Kundaje A, Batzoglou S, Snyder M (2012) Linking disease associations with regulatory information in the human genome. Genome Res 22(9):1748–1759. https://doi.org/10.1101/gr.136127.111
doi: 10.1101/gr.136127.111
pubmed: 22955986
pmcid: 3431491
Maurano MT, Humbert R, Rynes E, Thurman RE, Haugen E, Wang H, Reynolds AP, Sandstrom R, Qu H, Brody J, Shafer A, Neri F, Lee K, Kutyavin T, Stehling-Sun S, Johnson AK, Canfield TK, Giste E, Diegel M, Bates D, Hansen RS, Neph S, Sabo PJ, Heimfeld S, Raubitschek A, Ziegler S, Cotsapas C, Sotoodehnia N, Glass I, Sunyaev SR, Kaul R, Stamatoyannopoulos JA (2012) Systematic localization of common disease-associated variation in regulatory DNA. Science 337(6099):1190–1195. https://doi.org/10.1126/science.1222794
doi: 10.1126/science.1222794
pubmed: 22955828
pmcid: 22955828
Encode Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414):57–74. https://doi.org/10.1038/nature11247
doi: 10.1038/nature11247
Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, Ntini E, Arner E, Valen E, Li K, Schwarzfischer L, Glatz D, Raithel J, Lilje B, Rapin N, Bagger FO, Jorgensen M, Andersen PR, Bertin N, Rackham O, Burroughs AM, Baillie JK, Ishizu Y, Shimizu Y, Furuhata E, Maeda S, Negishi Y, Mungall CJ, Meehan TF, Lassmann T, Itoh M, Kawaji H, Kondo N, Kawai J, Lennartsson A, Daub CO, Heutink P, Hume DA, Jensen TH, Suzuki H, Hayashizaki Y, Muller F, Forrest ARR, Carninci P, Rehli M, Sandelin A (2014) An atlas of active enhancers across human cell types and tissues. Nature 507(7493):455–461. https://doi.org/10.1038/nature12787
doi: 10.1038/nature12787
pubmed: 24670763
pmcid: 24670763
Roadmap Epigenomics Consortium, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ, Amin V, Whitaker JW, Schultz MD, Ward LD, Sarkar A, Quon G, Sandstrom RS, Eaton ML, Wu YC, Pfenning AR, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris RA, Shoresh N, Epstein CB, Gjoneska E, Leung D, Xie W, Hawkins RD, Lister R, Hong C, Gascard P, Mungall AJ, Moore R, Chuah E, Tam A, Canfield TK, Hansen RS, Kaul R, Sabo PJ, Bansal MS, Carles A, Dixon JR, Farh KH, Feizi S, Karlic R, Kim AR, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer TR, Neph SJ, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari RC, Siebenthall KT, Sinnott-Armstrong NA, Stevens M, Thurman RE, Wu J, Zhang B, Zhou X, Beaudet AE, Boyer LA, De Jager PL, Farnham PJ, Fisher SJ, Haussler D, Jones SJ, Li W, Marra MA, McManus MT, Sunyaev S, Thomson JA, Tlsty TD, Tsai LH, Wang W, Waterland RA, Zhang MQ, Chadwick LH, Bernstein BE, Costello JF, Ecker JR, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA, Wang T, Kellis M (2015) Integrative analysis of 111 reference human epigenomes. Nature 518(7539):317–330. https://doi.org/10.1038/nature14248
doi: 10.1038/nature14248
Cherry TJ, Yang MG, Harmin DA, Tao P, Timms AE, Bauwens M, Allikmets R, Jones EM, Chen R, De Baere E, Greenberg ME (2020) Mapping the cis-regulatory architecture of the human retina reveals noncoding genetic variation in disease. Proc Natl Acad Sci U S A 117(16):9001–9012. https://doi.org/10.1073/pnas.1922501117
doi: 10.1073/pnas.1922501117
pubmed: 32265282
pmcid: 7183164
Waszak SM, Delaneau O, Gschwind AR, Kilpinen H, Raghav SK, Witwicki RM, Orioli A, Wiederkehr M, Panousis NI, Yurovsky A, Romano-Palumbo L, Planchon A, Bielser D, Padioleau I, Udin G, Thurnheer S, Hacker D, Hernandez N, Reymond A, Deplancke B, Dermitzakis ET (2015) Population variation and genetic control of modular chromatin architecture in humans. Cell 162(5):1039–1050. https://doi.org/10.1016/j.cell.2015.08.001
doi: 10.1016/j.cell.2015.08.001
pubmed: 26300124
pmcid: 26300124
Grubert F, Zaugg JB, Kasowski M, Ursu O, Spacek DV, Martin AR, Greenside P, Srivas R, Phanstiel DH, Pekowska A, Heidari N, Euskirchen G, Huber W, Pritchard JK, Bustamante CD, Steinmetz LM, Kundaje A, Snyder M (2015) Genetic control of chromatin states in humans involves local and distal chromosomal interactions. Cell 162(5):1051–1065. https://doi.org/10.1016/j.cell.2015.07.048
doi: 10.1016/j.cell.2015.07.048
pubmed: 26300125
pmcid: 26300125
Schoenfelder S, Fraser P (2019) Long-range enhancer-promoter contacts in gene expression control. Nat Rev Genet 20(8):437–455. https://doi.org/10.1038/s41576-019-0128-0
doi: 10.1038/s41576-019-0128-0
pubmed: 31086298
Calderon D, Bhaskar A, Knowles DA, Golan D, Raj T, Fu AQ, Pritchard JK (2017) Inferring relevant cell types for complex traits by using single-cell gene expression. Am J Hum Genet 101(5):686–699. https://doi.org/10.1016/j.ajhg.2017.09.009
doi: 10.1016/j.ajhg.2017.09.009
pubmed: 29106824
pmcid: 5673624
Linker SM, Urban L, Clark SJ, Chhatriwala M, Amatya S, McCarthy DJ, Ebersberger I, Vallier L, Reik W, Stegle O, Bonder MJ (2019) Combined single-cell profiling of expression and DNA methylation reveals splicing regulation and heterogeneity. Genome Biol 20(1):30. https://doi.org/10.1186/s13059-019-1644-0
doi: 10.1186/s13059-019-1644-0
pubmed: 30744673
pmcid: 6371455
Mizuno A, Okada Y (2019) Biological characterization of expression quantitative trait loci (eQTLs) showing tissue-specific opposite directional effects. Eur J Hum Genet. https://doi.org/10.1038/s41431-019-0468-4
GTEx Consortium; Laboratory, Data Analysis & Coordinating Center (LDACC)—Analysis Working Group; Statistical Methods groups—Analysis Working Group; Enhancing GTEx (eGTEx) groups; NIH Common Fund; NIH/NCI; NIH/NHGRI; NIH/NIMH; NIH/NIDA; Biospecimen Collection Source Site—NDRI; Biospecimen Collection Source Site—RPCI; Biospecimen Core Resource—VARI; Brain Bank Repository—University of Miami Brain Endowment Bank; Leidos Biomedical—Project Management; ELSI Study; Genome Browser Data Integration & Visualization—EBI; Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz; Lead analysts; Laboratory, Data Analysis &Coordinating Center (LDACC); NIH program management; Biospecimen collection; Pathology; eQTL Manuscript Working Group, Battle A, Brown CD, Engelhardt BE, Montgomery SB (2017) Genetic effects on gene expression across human tissues. Nature 550(7675):204–213. https://doi.org/10.1038/nature24277
doi: 10.1038/nature24277
Amin V, Harris RA, Onuchic V, Jackson AR, Charnecki T, Paithankar S, Lakshmi Subramanian S, Riehle K, Coarfa C, Milosavljevic A (2015) Epigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs. Nat Commun 6:6370. https://doi.org/10.1038/ncomms7370
doi: 10.1038/ncomms7370
pubmed: 25691256
pmcid: 4335353
Aken BL, Achuthan P, Akanni W, Amode MR, Bernsdorff F, Bhai J, Billis K, Carvalho-Silva D, Cummins C, Clapham P, Gil L, Giron CG, Gordon L, Hourlier T, Hunt SE, Janacek SH, Juettemann T, Keenan S, Laird MR, Lavidas I, Maurel T, McLaren W, Moore B, Murphy DN, Nag R, Newman V, Nuhn M, Ong CK, Parker A, Patricio M, Riat HS, Sheppard D, Sparrow H, Taylor K, Thormann A, Vullo A, Walts B, Wilder SP, Zadissa A, Kostadima M, Martin FJ, Muffato M, Perry E, Ruffier M, Staines DM, Trevanion SJ, Cunningham F, Yates A, Zerbino DR, Flicek P (2017) Ensembl 2017. Nucleic Acids Res 45(D1):D635–D642. https://doi.org/10.1093/nar/gkw1104
doi: 10.1093/nar/gkw1104
pubmed: 27899575
Bhalala OG, Nath AP, Consortium UKBE, Inouye M, Sibley CR (2018) Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue. PLoS Genet 14(8):e1007607. https://doi.org/10.1371/journal.pgen.1007607
doi: 10.1371/journal.pgen.1007607
pubmed: 30142156
pmcid: 6126875
Ratnapriya R, Sosina OA, Starostik MR, Kwicklis M, Kapphahn RJ, Fritsche LG, Walton A, Arvanitis M, Gieser L, Pietraszkiewicz A, Montezuma SR, Chew EY, Battle A, Abecasis GR, Ferrington DA, Chatterjee N, Swaroop A (2019) Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration. Nat Genet 51(4):606–610. https://doi.org/10.1038/s41588-019-0351-9
doi: 10.1038/s41588-019-0351-9
pubmed: 30742112
pmcid: 6441365
Gamazon ER, Wheeler HE, Shah KP, Mozaffari SV, Aquino-Michaels K, Carroll RJ, Eyler AE, Denny JC, GTEx Consortium, Nicolae DL, Cox NJ, Im HK (2015) A gene-based association method for mapping traits using reference transcriptome data. Nat Genet 47(9):1091–1098. https://doi.org/10.1038/ng.3367
doi: 10.1038/ng.3367
pubmed: 26258848
pmcid: 4552594
Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H (2009) Purinergic signalling in the nervous system: an overview. Trends Neurosci 32(1):19–29. https://doi.org/10.1016/j.tins.2008.10.001
doi: 10.1016/j.tins.2008.10.001
pubmed: 19008000
Hormozdiari F, van de Bunt M, Segre AV, Li X, Joo JWJ, Bilow M, Sul JH, Sankararaman S, Pasaniuc B, Eskin E (2016) Colocalization of GWAS and eQTL signals detects target genes. Am J Hum Genet 99(6):1245–1260. https://doi.org/10.1016/j.ajhg.2016.10.003
doi: 10.1016/j.ajhg.2016.10.003
pubmed: 27866706
pmcid: 5142122
Gusev A, Ko A, Shi H, Bhatia G, Chung W, Penninx BW, Jansen R, de Geus EJ, Boomsma DI, Wright FA, Sullivan PF, Nikkola E, Alvarez M, Civelek M, Lusis AJ, Lehtimaki T, Raitoharju E, Kahonen M, Seppala I, Raitakari OT, Kuusisto J, Laakso M, Price AL, Pajukanta P, Pasaniuc B (2016) Integrative approaches for large-scale transcriptome-wide association studies. Nat Genet 48(3):245–252. https://doi.org/10.1038/ng.3506
doi: 10.1038/ng.3506
pubmed: 26854917
pmcid: 4767558
Wainberg M, Sinnott-Armstrong N, Mancuso N, Barbeira AN, Knowles DA, Golan D, Ermel R, Ruusalepp A, Quertermous T, Hao K, Bjorkegren JLM, Im HK, Pasaniuc B, Rivas MA, Kundaje A (2019) Opportunities and challenges for transcriptome-wide association studies. Nat Genet 51(4):592–599. https://doi.org/10.1038/s41588-019-0385-z
doi: 10.1038/s41588-019-0385-z
pubmed: 30926968
pmcid: 6777347
Inoue F, Ahituv N (2015) Decoding enhancers using massively parallel reporter assays. Genomics 106(3):159–164. https://doi.org/10.1016/j.ygeno.2015.06.005
doi: 10.1016/j.ygeno.2015.06.005
pubmed: 26072433
pmcid: 26072433
Patwardhan RP, Hiatt JB, Witten DM, Kim MJ, Smith RP, May D, Lee C, Andrie JM, Lee SI, Cooper GM, Ahituv N, Pennacchio LA, Shendure J (2012) Massively parallel functional dissection of mammalian enhancers in vivo. Nat Biotechnol 30(3):265–270. https://doi.org/10.1038/nbt.2136
doi: 10.1038/nbt.2136
pubmed: 22371081
pmcid: 3402344
Spisak S, Lawrenson K, Fu Y, Csabai I, Cottman RT, Seo JH, Haiman C, Han Y, Lenci R, Li Q, Tisza V, Szallasi Z, Herbert ZT, Chabot M, Pomerantz M, Solymosi N, GliomaScan Consortium, Gayther SA, Joung JK, Freedman ML (2015) CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants. Nat Med 21(11):1357–1363. https://doi.org/10.1038/nm.3975
doi: 10.1038/nm.3975
pubmed: 26398868
pmcid: 4746056
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y, FANTOM Consortium; RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group) (2005) The transcriptional landscape of the mammalian genome. Science 309(5740):1559–1563. https://doi.org/10.1126/science.1112014
doi: 10.1126/science.1112014
pubmed: 16141072
Pennesi ME, Michaels KV, Magee SS, Maricle A, Davin SP, Garg AK, Gale MJ, Tu DC, Wen Y, Erker LR, Francis PJ (2012) Long-term characterization of retinal degeneration in rd1 and rd10 mice using spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 53(8):4644–4656. https://doi.org/10.1167/iovs.12-9611
doi: 10.1167/iovs.12-9611
pubmed: 22562504
pmcid: 3394742
Fletcher EL, Jobling AI, Greferath U, Mills SA, Waugh M, Ho T, de Iongh RU, Phipps JA, Vessey KA (2014) Studying age-related macular degeneration using animal models. Optom Vis Sci 91(8):878–886. https://doi.org/10.1097/OPX.0000000000000322
doi: 10.1097/OPX.0000000000000322
pubmed: 24978866
pmcid: 4186726
Rudolf M, Winkler B, Aherrahou Z, Doehring LC, Kaczmarek P, Schmidt-Erfurth U (2005) Increased expression of vascular endothelial growth factor associated with accumulation of lipids in Bruch’s membrane of LDL receptor knockout mice. Br J Ophthalmol 89(12):1627–1630. https://doi.org/10.1136/bjo.2005.071183
doi: 10.1136/bjo.2005.071183
pubmed: 16299144
pmcid: 1772995
Coffey PJ, Gias C, McDermott CJ, Lundh P, Pickering MC, Sethi C, Bird A, Fitzke FW, Maass A, Chen LL, Holder GE, Luthert PJ, Salt TE, Moss SE, Greenwood J (2007) Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction. Proc Natl Acad Sci U S A 104(42):16651–16656
doi: 10.1073/pnas.0705079104
Nozaki M, Raisler BJ, Sakurai E, Sarma JV, Barnum SR, Lambris JD, Chen Y, Zhang K, Ambati BK, Baffi JZ, Ambati J (2006) Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci U S A 103(7):2328–2333
doi: 10.1073/pnas.0408835103
Combadiere C, Feumi C, Raoul W, Keller N, Rodero M, Pezard A, Lavalette S, Houssier M, Jonet L, Picard E, Debre P, Sirinyan M, Deterre P, Ferroukhi T, Cohen SY, Chauvaud D, Jeanny JC, Chemtob S, Behar-Cohen F, Sennlaub F (2007) CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration. J Clin Invest 117(10):2920–2928
doi: 10.1172/JCI31692
Cousins SW, Espinosa-Heidmann DG, Alexandridou A, Sall J, Dubovy S, Csaky K (2002) The role of aging, high fat diet and blue light exposure in an experimental mouse model for basal laminar deposit formation. Exp Eye Res 75(5):543–553. https://doi.org/10.1006/exer.2002.2047
doi: 10.1006/exer.2002.2047
pubmed: 12457866
Espinosa-Heidmann DG, Suner IJ, Catanuto P, Hernandez EP, Marin-Castano ME, Cousins SW (2006) Cigarette smoke-related oxidants and the development of sub-RPE deposits in an experimental animal model of dry AMD. Invest Ophthalmol Vis Sci 47(2):729–737
doi: 10.1167/iovs.05-0719
Eiraku M, Adachi T, Sasai Y (2012) Relaxation-expansion model for self-driven retinal morphogenesis: a hypothesis from the perspective of biosystems dynamics at the multi-cellular level. BioEssays 34(1):17–25. https://doi.org/10.1002/bies.201100070
doi: 10.1002/bies.201100070
pubmed: 22052700
pmcid: 3266490
Nakano T, Ando S, Takata N, Kawada M, Muguruma K, Sekiguchi K, Saito K, Yonemura S, Eiraku M, Sasai Y (2012) Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10(6):771–785. https://doi.org/10.1016/j.stem.2012.05.009
doi: 10.1016/j.stem.2012.05.009
pubmed: 22704518
Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K (2016) Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci 73(9):1765–1786. https://doi.org/10.1007/s00018-016-2147-8
doi: 10.1007/s00018-016-2147-8
pubmed: 26852158
pmcid: 4819943
Ambati J, Atkinson JP, Gelfand BD (2013) Immunology of age-related macular degeneration. Nat Rev Immunol 13(6):438–451. https://doi.org/10.1038/nri3459
doi: 10.1038/nri3459
pubmed: 23702979
pmcid: 3941009