Association of low-frequency and rare coding variants with information processing speed.

Adult Aging Cognition Genome-Wide Association Study Geroscience Humans Polymorphism, Single Nucleotide Ubiquitin-Protein Ligases

Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
04 12 2021
Historique:
received: 12 08 2020
accepted: 10 11 2021
revised: 20 10 2021
entrez: 5 12 2021
pubmed: 6 12 2021
medline: 1 2 2022
Statut: epublish

Résumé

Measures of information processing speed vary between individuals and decline with age. Studies of aging twins suggest heritability may be as high as 67%. The Illumina HumanExome Bead Chip genotyping array was used to examine the association of rare coding variants with performance on the Digit-Symbol Substitution Test (DSST) in community-dwelling adults participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. DSST scores were available for 30,576 individuals of European ancestry from nine cohorts and for 5758 individuals of African ancestry from four cohorts who were older than 45 years and free of dementia and clinical stroke. Linear regression models adjusted for age and gender were used for analysis of single genetic variants, and the T5, T1, and T01 burden tests that aggregate the number of rare alleles by gene were also applied. Secondary analyses included further adjustment for education. Meta-analyses to combine cohort-specific results were carried out separately for each ancestry group. Variants in RNF19A reached the threshold for statistical significance (p = 2.01 × 10

Identifiants

DOI: 10.1038/s41398-021-01736-6 PMID: 34864818 PMC: PMC8643353
pubmed: 34864818
doi: 10.1038/s41398-021-01736-6
pii: 10.1038/s41398-021-01736-6
pmc: PMC8643353
doi:

Substances chimiques

RNF19A protein, human EC 2.3.2.27
Ubiquitin-Protein Ligases EC 2.3.2.27

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

613

Subventions

Organisme : NIA NIH HHS
ID : R01 AG054076
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS087541
Pays : United States
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL093029
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004729
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG033193
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG063887
Pays : United States
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

Références

Deary IJ, Penke L, Johnson W. The neuroscience of human intelligence differences. Nat Rev Neurosci. 2010;11:201–11.
pubmed: 20145623 doi: 10.1038/nrn2793
Salthouse TA. The processing-speed theory of adult age differences in cognition. Psychol Rev. 1996;103:403–28.
pubmed: 8759042 doi: 10.1037/0033-295X.103.3.403
Der G, Deary IJ. Age and sex differences in reaction time in adulthood: results from the United Kingdom Health and Lifestyle Survey. Psychol Aging. 2006;21:62–73.
pubmed: 16594792 doi: 10.1037/0882-7974.21.1.62
Lopez OL, Jagust WJ, Dulberg C, Becker JT, DeKosky ST, Fitzpatrick A, et al. Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2. Arch Neurol. 2003;60:1394–9.
pubmed: 14568809 doi: 10.1001/archneur.60.10.1394
Twamley EW, Ropacki SA, Bondi MW. Neuropsychological and neuroimaging changes in preclinical Alzheimer’s disease. J Int Neuropsychol Soc. 2006;12:707–35.
pubmed: 16961952 pmcid: 1621044 doi: 10.1017/S1355617706060863
Reitz C, Mayeux R. Endophenotypes in normal brain morphology and Alzheimer’s disease: a review. Neuroscience. 2009;164:174–90.
pubmed: 19362127 doi: 10.1016/j.neuroscience.2009.04.006
Wilson RS, Bienias JL, Berry-Kravis E, Evans DA, Bennett DA. The apolipoprotein E epsilon 2 allele and decline in episodic memory. J Neurol Neurosurg Psychiatry. 2002;73:672–7.
pubmed: 12438469 pmcid: 1757351 doi: 10.1136/jnnp.73.6.672
Dickinson D, Ramsey ME, Gold JM. Overlooking the obvious: a meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Arch Gen Psychiatry. 2007;64:532–42.
pubmed: 17485605 doi: 10.1001/archpsyc.64.5.532
Bidwell LC, Willcutt EG, Defries JC, Pennington BF. Testing for neuropsychological endophenotypes in siblings discordant for attention-deficit/hyperactivity disorder. Biol Psychiatry. 2007;62:991–8.
pubmed: 17585884 pmcid: 2687149 doi: 10.1016/j.biopsych.2007.04.003
Deary IJ. Looking down on human intelligence: from psychometrics to the brain. New York, NY: Oxford University Press; 2000.
Swan GE, Carmelli D, Reed T, Harshfield GA, Fabsitz RR, Eslinger PJ. Heritability of cognitive performance in aging twins. The National Heart, Lung, and Blood Institute Twin Study. Arch Neurol. 1990;47:259–62.
pubmed: 2310310 doi: 10.1001/archneur.1990.00530030025010
McClearn GE, Johansson B, Berg S, Pedersen NL, Ahern F, Petrill SA, et al. Substantial genetic influence on cognitive abilities in twins 80 or more years old. Science. 1997;276:1560–3.
pubmed: 9171059 doi: 10.1126/science.276.5318.1560
Finkel D, Pedersen NL. Contribution of age, genes, and environment to the relationship between perceptual speed and cognitive ability. Psychol Aging. 2000;15:56–64.
pubmed: 10755289 doi: 10.1037/0882-7974.15.1.56
Swan GE, Carmelli D. Evidence for genetic mediation of executive control: a study of aging male twins. J Gerontol B Psychol Sci Soc Sci. 2002;57:P133–43.
pubmed: 11867661 doi: 10.1093/geronb/57.2.P133
Luciano M, Hansell NK, Lahti J, Davies G, Medland SE, Räikkönen K, et al. Whole genome association scan for genetic polymorphisms influencing information processing speed. Biol Psychol. 2011;86:193–202.
pubmed: 21130836 doi: 10.1016/j.biopsycho.2010.11.008
Cirulli ET, Kasperaviciūte D, Attix DK, Need AC, Ge D, Gibson G, et al. Common genetic variation and performance on standardized cognitive tests. Eur J Hum Genet. 2010;18:815–20.
pubmed: 20125193 pmcid: 2987367 doi: 10.1038/ejhg.2010.2
Ibrahim-Verbaas CA, Bressler J, Debette S, Schuur M, Smith AV, Bis JC, et al. GWAS for executive function and processing speed suggests involvement of the CADM2 gene. Mol Psychiatry. 2016;21:189–97.
pubmed: 25869804 doi: 10.1038/mp.2015.37
Davies G, Marioni RE, Liewald DC, Hill WD, Hagenaars SP, Harris SE, et al. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N = 112 151). Mol Psychiatry. 2016;21:758–67.
pubmed: 27046643 pmcid: 4879186 doi: 10.1038/mp.2016.45
Grove ML, Yu B, Cochran BJ, Haritunians T, Bis JC, Taylor KD, et al. Best practices and joint calling of the HumanExome BeadChip: the CHARGE Consortium. PLoS ONE. 2013;8:e68095.
pubmed: 23874508 pmcid: 3709915 doi: 10.1371/journal.pone.0068095
Psaty BM, O’Donnell CJ, Gudnason V, Lunetta KL, Folsom AR, Rotter JI, et al. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circ Cardiovasc Genet. 2009;2:73–80.
pubmed: 20031568 pmcid: 2875693 doi: 10.1161/CIRCGENETICS.108.829747
Wechsler D. Wechsler adult intelligence scale-revised. New York: Psychological Corporation; 1981.
Wechsler D. Manual for the Wechsler Adult Intelligence Scale. New York: Psychological Corporation; 1955.
Wechsler D. WAIS-III UK administration and scoring manual. London: Psychological Corporation; 1998.
Wechsler D. Wechsler Adult Intelligence Scale-III (WAIS-III). New York: Psychological Corporation; 1997.
Li B, Leal SM. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am J Hum Genet. 2008;83:311–21.
pubmed: 18691683 pmcid: 2842185 doi: 10.1016/j.ajhg.2008.06.024
Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26:2190–1.
pubmed: 20616382 pmcid: 2922887 doi: 10.1093/bioinformatics/btq340
Logue MW, Schu M, Vardarajan BN, Farrell J, Bennett DA, Buxbaum JD, et al. Two rare AKAP9 variants are associated with Alzheimer’s disease in African Americans. Alzheimers Dement. 2014;10:609–18.e11.
pubmed: 25172201 pmcid: 4253055 doi: 10.1016/j.jalz.2014.06.010
N’Songo A, Carrasquillo MM, Wang X, Burgess JD, Nguyen T, Asmann YW, et al. African American exome sequencing identifies potential risk variants at Alzheimer disease loci. Neurol Genet. 2017;3:e141.
pubmed: 28480329 pmcid: 5406839 doi: 10.1212/NXG.0000000000000141
Sims R, van der Lee SJ, Naj AC, Bellenguez C, Badarinarayan N, Jakobsdottir J, et al. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat Genet. 2017;49:1373–84.
pubmed: 28714976 pmcid: 5669039 doi: 10.1038/ng.3916
Vardarajan BN, Ghani M, Kahn A, Sheikh S, Sato C, Barral S, et al. Rare coding mutations identified by sequencing of Alzheimer disease genome-wide association studies loci. Ann Neurol. 2015;78:487–98.
pubmed: 26101835 pmcid: 4546546 doi: 10.1002/ana.24466
Bis JC, Jian X, Kunkle BW, Chen Y, Hamilton-Nelson KL, Bush WS, et al. Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation. Mol Psychiatry.2020;25:1859–75.
pubmed: 30108311 doi: 10.1038/s41380-018-0112-7
Raghavan NS, Brickman AM, Andrews H, Manly JJ, Schupf N, Lantigua R, et al. Whole-exome sequencing in 20,197 persons for rare variants in Alzheimer’s disease. Ann Clin Transl Neurol. 2018;5:832–42.
pubmed: 30009200 pmcid: 6043775 doi: 10.1002/acn3.582
Patel D, Mez J, Vardarajan BN, Staley L, Chung J, Zhang X, et al. Association of rare coding mutations with Alzheimer disease and other dementias among adults of European ancestry. JAMA Netw Open. 2019;2:e191350.
pubmed: 30924900 pmcid: 6450321 doi: 10.1001/jamanetworkopen.2019.1350
GTEx Consortium. The genotype-tissue expression (GTEx) project. Nat Genet. 2013;45:580–5.
doi: 10.1038/ng.2653
Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, et al. Spatio-temporal transcriptome of the human brain. Nature. 2011;478:483–9.
pubmed: 22031440 pmcid: 3566780 doi: 10.1038/nature10523
Watanabe K, Taskesen E, van Bochoven A, Posthuma D. Functional mapping and annotation of genetic associations with FUMA. Nat Commun. 2017;8:1826.
pubmed: 29184056 pmcid: 5705698 doi: 10.1038/s41467-017-01261-5
Liberzon A, Subramanian A, Pinchback R, Thorvaldsdóttir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27:1739–40.
pubmed: 21546393 pmcid: 3106198 doi: 10.1093/bioinformatics/btr260
Kutmon M, Riutta A, Nunes N, Hanspers K, Willighagen EL, Bohler A, et al. WikiPathways: capturing the full diversity of pathway knowledge. Nucleic Acids Res. 2016;44:D488–94.
pubmed: 26481357 doi: 10.1093/nar/gkv1024
Kramer A, Green J, Pollard J Jr, Tugendreich S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics. 2014;30:523–30.
pubmed: 24336805 doi: 10.1093/bioinformatics/btt703
Pate DS, Margolin DI. Cognitive slowing in Parkinson’s and Alzheimer’s patients: distinguishing bradyphrenia from dementia. Neurology. 1994;44:669–74.
pubmed: 8164823 doi: 10.1212/WNL.44.4.669
Peavy GM, Salmon D, Bear PI, Paulsen JS, Cahn DA, Hofstetter CR, et al. Detection of mild cognitive deficits in Parkinson’s disease patients with the WAIS-R NI. J Int Neuropsychol Soc. 2001;7:535–43.
pubmed: 11459105 doi: 10.1017/S1355617701755014
Ito T, Niwa J, Hishikawa N, Ishigaki S, Doyu M, Sobue G. Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1. J Biol Chem. 2003;278:29106–14.
pubmed: 12750386 doi: 10.1074/jbc.M302763200
Niwa J, Ishigaki S, Hishikawa N, Yamamoto M, Doyu M, Murata S, et al. Dorfin ubiquitylates mutant SOD1 and prevents mutant SOD1-mediated neurotoxicity. J Biol Chem. 2002;277:36793–8.
pubmed: 12145308 doi: 10.1074/jbc.M206559200
Cropp CD, Komori T, Shima JE, Urban TJ, Yee SW, More SS, et al. Organic anion transporter 2 (SLC22A7) is a facilitative transporter of cGMP. Mol Pharmacol. 2008;73:1151–8.
pubmed: 18216183 doi: 10.1124/mol.107.043117
Jolles J, Houx P, van Boxtel M, Ponds R. The Maastricht aging study: determinants of cognitive aging. Maastricht: Neuropsych Publishers; 1995.
Lezak M. Neuropsychological assessment. New York: Oxford University Press; 1995.
Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet. 2019;51:414–30.
pubmed: 30820047 pmcid: 6463297 doi: 10.1038/s41588-019-0358-2
Croft D, Mundo AF, Haw R, Milacic M, Weiser J, Wu G, et al. The Reactome pathway knowledgebase. Nucleic Acids Res. 2014;42:D472–7.
pubmed: 24243840 doi: 10.1093/nar/gkt1102
Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28:27–30.
pubmed: 10592173 pmcid: 102409 doi: 10.1093/nar/28.1.27
Ciechanover A, Heller H, Katz-Etzion R, Hershko A. Activation of the heat-stable polypeptide of the ATP-dependent proteolytic system. Proc Natl Acad Sci USA. 1981;78:761–5.
pubmed: 6262770 pmcid: 319882 doi: 10.1073/pnas.78.2.761
Hershko A, Heller H, Elias S, Ciechanover A. Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J Biol Chem. 1983;258:8206–14.
pubmed: 6305978 doi: 10.1016/S0021-9258(20)82050-X
George AJ, Hoffiz YC, Charles AJ, Zhu Y, Mabb AM. A comprehensive atlas of E3 ubiquitin ligase mutations in neurological disorders. Front Genet. 2018;9:29.
pubmed: 29491882 pmcid: 5817383 doi: 10.3389/fgene.2018.00029
Niwa J, Ishigaki S, Doyu M, Suzuki T, Tanaka K, Sobue G. A novel centrosomal ring-finger protein, dorfin, mediates ubiquitin ligase activity. Biochem Biophys Res Commun. 2001;281:706–13.
pubmed: 11237715 doi: 10.1006/bbrc.2001.4414
Park H, Yang J, Kim R, Li Y, Lee Y, Lee C, et al. Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning. Sci Rep. 2015;5:16410.
pubmed: 26553645 pmcid: 4639748 doi: 10.1038/srep16410
Hishikawa N, Niwa J, Doyu M, Ito T, Ishigaki S, Hashizume Y, et al. Dorfin localizes to the ubiquitylated inclusions in Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy, and amyotrophic lateral sclerosis. Am J Pathol. 2003;163:609–19.
pubmed: 12875980 pmcid: 1868225 doi: 10.1016/S0002-9440(10)63688-7
Takeuchi H, Niwa J, Hishikawa N, Ishigaki S, Tanaka F, Doyu M, et al. Dorfin prevents cell death by reducing mitochondrial localizing mutant superoxide dismutase 1 in a neuronal cell model of familial amyotrophic lateral sclerosis. J Neurochem. 2004;89:64–72.
pubmed: 15030390 doi: 10.1046/j.1471-4159.2003.02289.x
Ishigaki S, Hishikawa N, Niwa J, Iemura S, Natsume T, Hori S, et al. Physical and functional interaction between Dorfin and Valosin-containing protein that are colocalized in ubiquitylated inclusions in neurodegenerative disorders. J Biol Chem. 2004;279:51376–85.
pubmed: 15456787 doi: 10.1074/jbc.M406683200
Niwa J, Yamada S, Ishigaki S, Sone J, Takahashi M, Katsuno M, et al. Disulfide bond mediates aggregation, toxicity, and ubiquitylation of familial amyotrophic lateral sclerosis-linked mutant SOD1. J Biol Chem. 2007;282:28087–95.
pubmed: 17666395 doi: 10.1074/jbc.M704465200
Dasgupta S, Lonard DM, O’Malley BW. Nuclear receptor coactivators: master regulators of human health and disease. Annu Rev Med. 2014;65:279–92.
pubmed: 24111892 doi: 10.1146/annurev-med-051812-145316
Chai Z, Yang L, Yu B, He Q, Li WI, Zhou R, et al. p38 mitogen-activated protein kinase-dependent regulation of SRC-3 and involvement in retinoic acid receptor alpha signaling in embryonic cortical neurons. IUBMB Life. 2009;61:670–8.
pubmed: 19472184 doi: 10.1002/iub.212
Tetel MJ, Acharya KD. Nuclear receptor coactivators: regulators of steroid action in brain and behaviour. J Neuroendocrinol. 2013;25:1209–18.
pubmed: 23795583 pmcid: 3830605 doi: 10.1111/jne.12065
Sun Z, Xu Y. Nuclear receptor coactivators (NCOAs) and corepressors (NCORs) in the brain. Endocrinology. 2020;161:1–12.
doi: 10.1210/endocr/bqaa083
Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteom. 2014;13:397–406.
doi: 10.1074/mcp.M113.035600
Reitz C, Tang MX, Schupf N, Manly JJ, Mayeux R, Luchsinger JA. Association of higher levels of high-density lipoprotein cholesterol in elderly individuals and lower risk of late-onset Alzheimer disease. Arch Neurol. 2010;67:1491–7.
pubmed: 21149810 pmcid: 3065942 doi: 10.1001/archneurol.2010.297
Richardson TG, Sanderson E, Palmer TM, Ala-Korpela M, Ference BA, Davey Smith G, et al. Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: a multivariable Mendelian randomisation analysis. PLoS Med. 2020;17:e1003062.
pubmed: 32203549 pmcid: 7089422 doi: 10.1371/journal.pmed.1003062
Arvanitakis Z, Capuano AW, Lamar M, Shah RC, Barnes LL, Bennett DA, et al. Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology. 2018;91:e517–25.
pubmed: 29997190 pmcid: 6105052 doi: 10.1212/WNL.0000000000005951
Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, et al. Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nat Genet. 2018;50:1412–25.
pubmed: 30224653 pmcid: 6284793 doi: 10.1038/s41588-018-0205-x
Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology. 1999;53:1937–42.
pubmed: 10599761 doi: 10.1212/WNL.53.9.1937
Knopman D, Boland LL, Mosley T, Howard G, Liao D, Szklo M, et al. Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology. 2001;56:42–8.
pubmed: 11148234 doi: 10.1212/WNL.56.1.42
Peila R, Rodriguez BL, Launer LJ. Honolulu-Asia Aging Study. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes. 2002;51:1256–62.
pubmed: 11916953 doi: 10.2337/diabetes.51.4.1256
Mahajan A, Wessel J, Willems SM, Zhao W, Robertson NR, Chu AY, et al. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes. Nat Genet. 2018;50:559–71.
pubmed: 29632382 pmcid: 5898373 doi: 10.1038/s41588-018-0084-1
Vujkovic M, Keaton JM, Lynch JA, Miller DR, Zhou J, Tcheandjieu C, et al. Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis. Nat Genet. 2020;52:680–91.
pubmed: 32541925 pmcid: 7343592 doi: 10.1038/s41588-020-0637-y
Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S, et al. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet. 2014;46:1173–86.
pubmed: 25282103 pmcid: 4250049 doi: 10.1038/ng.3097
Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197–206.
pubmed: 25673413 pmcid: 4382211 doi: 10.1038/nature14177

Auteurs

Jan Bressler (J)

Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA. jan.bressler@uth.tmc.edu.
ORCID: 0000-0001-6578-4772

Gail Davies (G)

Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0003-1120-7026

Albert V Smith (AV)

Icelandic Heart Association, Kopavogur, Iceland.

Yasaman Saba (Y)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria.

Joshua C Bis (JC)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

Xueqiu Jian (X)

Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.

Caroline Hayward (C)

Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0002-9405-9550

Lisa Yanek (L)

Department of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
ORCID: 0000-0001-7117-1075

Jennifer A Smith (JA)

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
ORCID: 0000-0002-3575-5468

Saira S Mirza (SS)

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Department of Medicine, University of Toronto, Toronto, ON, Canada.

Ruiqi Wang (R)

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Framingham Heart Study, Framingham, MA, USA.

Hieab H H Adams (HHH)

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, Vrieje Universiteit Medical Center, Amsterdam, The Netherlands.
ORCID: 0000-0003-3687-2508

Diane Becker (D)

Department of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Eric Boerwinkle (E)

Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.

Archie Campbell (A)

Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Usher Institute, University of Edinburgh, Edinburgh, UK.
Health Data Research UK, University of Edinburgh, Edinburgh, UK.

Simon R Cox (SR)

Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0003-4036-3642

Gudny Eiriksdottir (G)

Icelandic Heart Association, Kopavogur, Iceland.

Chloe Fawns-Ritchie (C)

Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.

Rebecca F Gottesman (RF)

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
ORCID: 0000-0002-9504-1256

Megan L Grove (ML)

Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
ORCID: 0000-0001-6764-2508

Xiuqing Guo (X)

The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

Edith Hofer (E)

Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.

Sharon L R Kardia (SLR)

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.

Maria J Knol (MJ)

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
ORCID: 0000-0002-3597-1531

Marisa Koini (M)

Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.

Oscar L Lopez (OL)

Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
ORCID: 0000-0002-8546-8256

Riccardo E Marioni (RE)

Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.

Paul Nyquist (P)

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Alison Pattie (A)

Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.

Ozren Polasek (O)

Faculty of Medicine, University of Split, Split, Croatia.
Gen-Info Ltd, Zagreb, Croatia.

David J Porteous (DJ)

Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.

Igor Rudan (I)

Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.

Claudia L Satizabal (CL)

Framingham Heart Study, Framingham, MA, USA.
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA.
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
ORCID: 0000-0002-1115-4430

Helena Schmidt (H)

Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria.

Reinhold Schmidt (R)

Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.

Stephen Sidney (S)

Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.

Jeannette Simino (J)

Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.

Blair H Smith (BH)

Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
ORCID: 0000-0002-5362-9430

Stephen T Turner (ST)

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.

Sven J van der Lee (SJ)

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
ORCID: 0000-0003-1606-8643

Erin B Ware (EB)

Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.

Rachel A Whitmer (RA)

Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.

Kristine Yaffe (K)

Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA.

Qiong Yang (Q)

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Framingham Heart Study, Framingham, MA, USA.

Wei Zhao (W)

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
ORCID: 0000-0001-7388-0692

Vilmundur Gudnason (V)

Icelandic Heart Association, Kopavogur, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Lenore J Launer (LJ)

Laboratory of Epidemiology and Population Science, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-3238-7612

Annette L Fitzpatrick (AL)

Department of Family Medicine, University of Washington, Seattle, WA, USA.
Department of Epidemiology, University of Washington, Seattle, WA, USA.

Bruce M Psaty (BM)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Department of Health Services, University of Washington, Seattle, WA, USA.

Myriam Fornage (M)

Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
ORCID: 0000-0003-0677-8158

M Arfan Ikram (M)

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
ORCID: 0000-0003-0372-8585

Cornelia M van Duijn (CM)

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Public Health, Oxford University, Oxford, UK.

Sudha Seshadri (S)

Framingham Heart Study, Framingham, MA, USA.
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA.
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.

Thomas H Mosley (TH)

Division of Geriatrics, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Ian J Deary (IJ)

Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0002-1733-263X

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Association of low-frequency and rare coding...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Association of low-frequency and rare coding...
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Cognition › Association of low-frequency and rare coding...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Association of low-frequency and rare coding...
questionsmedicales.fr › Professions de santé › Médecine › Gériatrie › Géroscience › Association of low-frequency and rare coding...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Association of low-frequency and rare coding...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Association of low-frequency and rare coding...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Association of low-frequency and rare coding...