Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia.
cascade screening
familial hypercholesterolemia
genomics-guided disease management
population-based biobank
recall by genotype
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
22
06
2018
accepted:
06
09
2018
pubmed:
3
10
2018
medline:
14
2
2020
entrez:
2
10
2018
Statut:
ppublish
Résumé
Large-scale, population-based biobanks integrating health records and genomic profiles may provide a platform to identify individuals with disease-predisposing genetic variants. Here, we recall probands carrying familial hypercholesterolemia (FH)-associated variants, perform cascade screening of family members, and describe health outcomes affected by such a strategy. The Estonian Biobank of Estonian Genome Center, University of Tartu, comprises 52,274 individuals. Among 4776 participants with exome or genome sequences, we identified 27 individuals who carried FH-associated variants in the LDLR, APOB, or PCSK9 genes. Cascade screening of 64 family members identified an additional 20 carriers of FH-associated variants. Via genetic counseling and clinical management of carriers, we were able to reclassify 51% of the study participants from having previously established nonspecific hypercholesterolemia to having FH and identify 32% who were completely unaware of harboring a high-risk disease-associated genetic variant. Imaging-based risk stratification targeted 86% of the variant carriers for statin treatment recommendations. Genotype-guided recall of probands and subsequent cascade screening for familial hypercholesterolemia is feasible within a population-based biobank and may facilitate more appropriate clinical management.
Identifiants
pubmed: 30270359
doi: 10.1038/s41436-018-0311-2
pii: S1098-3600(21)01484-2
pmc: PMC6443485
mid: NIHMS994784
doi:
Substances chimiques
APOB protein, human
0
Apolipoprotein B-100
0
LDLR protein, human
0
Receptors, LDL
0
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1173-1180Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL140203
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK075787
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142711
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007205
Pays : United States
Références
Corbin LJ, Tan VY, Hughes DA, et al. Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference. Nat Commun. 2018;9:711.
doi: 10.1038/s41467-018-03109-y
Stessman HA, Bernier R, Eichler EE. A genotype-first approach to defining the subtypes of a complex disease. Cell. 2014;156:872–877.
doi: 10.1016/j.cell.2014.02.002
Stessman HAF, Xiong B, Coe BP, et al. Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet. 2017;49:515–526.
doi: 10.1038/ng.3792
Benn M, Watts GF, Tybjærg-Hansen A, Nordestgaard BG. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. Eur Heart J. 2016;37:1384–1394.
doi: 10.1093/eurheartj/ehw028
Gidding SS, Champagne MA, de Ferranti SD. et al. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association. Circulation. 2015;132:2167–2192.
doi: 10.1161/CIR.0000000000000297
Goldstein JK, Hobbs HHBM. Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle DThe metabolic & molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001. p. 2863–2913.
Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: A HuGE prevalence review. Am J Epidemiol. 2004;160:407–420.
doi: 10.1093/aje/kwh236
Khera AV, Won HH, Peloso GM, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67:2578–2589.
doi: 10.1016/j.jacc.2016.03.520
Abul-Husn NS, Manickam K, Jones LK, et al. Genetic identification of familial hypercholesterolemia within a single U.S. health care system. Science. 2016;354:aaf7000.
doi: 10.1126/science.aaf7000
Leitsalu L, Haller T, Esko T, et al. Cohort profile: Estonian Biobank of the Estonian Genome Center, University of Tartu. Int J Epidemiol. 2015;44:1137–1147.
doi: 10.1093/ije/dyt268
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–1760.
doi: 10.1093/bioinformatics/btp324
McLaren W, Gil L, Hunt SE, et al. The Ensembl Variant Effect Predictor. Genome Biol. 2016;17:122.
doi: 10.1186/s13059-016-0974-4
Yang H, Wang K. Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR. Nat Protoc. 2015;10:1556–1566.
doi: 10.1038/nprot.2015.105
Kulkarni KR, Garber DW, Marcovina SM, Segrest JP. Quantification of cholesterol in all lipoprotein classes by the VAP-II method. J Lipid Res. 1994;35:159–168.
pubmed: 8138718
Kulkarni KR. Cholesterol profile measurement by vertical auto profile method. Clin Lab Med. 2006;26:787–802.
doi: 10.1016/j.cll.2006.07.004
Peloso GM, Auer PL, Bis JC, et al. Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks. Am J Hum Genet. 2014;94:223–232.
doi: 10.1016/j.ajhg.2014.01.009
Defesche JC, Lansberg PJ, Umans-Eckenhausen MAKJ. Advanced method for the identification of patients with inherited hypercholesterolemia. Semin Vasc Med. 2004;4:59–65.
doi: 10.1055/s-2004-822987
Catapano AL, Graham I, De Backer G. et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999–3058l.
doi: 10.1093/eurheartj/ehw272
Borén J, Lee I, Zhu W, Arnold K, Taylor S, Innerarity TL. Identification of the low density lipoprotein receptor-binding site in apolipoprotein B100 and the modulation of its binding activity by the carboxyl terminus in familial defective Apo-B100. J Clin Invest. 1998;101:1084–1093.
doi: 10.1172/JCI1847
Landrum MJ, Lee JM, Riley GR. et al. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids. 2014;42:D980–D985.
doi: 10.1093/nar/gkt1113
Ziyatdinov A, Vázquez-Santiago M, Brunel H, Martinez-perez A, Aschard H, Soria JM. Lme4Qtl: linear mixed models with flexible covariance structure for genetic studies of related individuals. BMC Bioinformatics. 2018;19:68.
doi: 10.1186/s12859-018-2057-x
R Core Team. R: A language and environment for statistical computing. 2013. Foundation for Statistical Computing. Vienna, Austria. http://www.R-project.org/ .
McClelland RL, Chung H, Detrano R, Post W, Kronmal RA. Distribution of coronary artery calcium by race, gender, and age. Circulation. 2006;113:30 LP–37.
doi: 10.1161/CIRCULATIONAHA.105.580696
Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Eur Heart J. 2013;34:3478–3490.
doi: 10.1093/eurheartj/eht273
Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. Br Med J. 1991;303:893–896.
doi: 10.1136/bmj.303.6807.893
Williams RR, Hunt SC, Schumacher MC, et al. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol. 1993;72:171–176.
doi: 10.1016/0002-9149(93)90155-6
Bertolini S, Pisciotta L, Rabacchi C, et al. Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy. Atherosclerosis. 2013;227:342–348.
doi: 10.1016/j.atherosclerosis.2013.01.007
De Isla LP, Alonso R, Mata N. et al. Coronary heart disease, peripheral arterial disease, and stroke in familial hypercholesterolaemia: Insights from the SAFEHEART registry (Spanish familial hypercholesterolaemia cohort study). Arterioscler Thromb Vasc Biol. 2016;36:2004–2010.
doi: 10.1161/ATVBAHA.116.307514
Sjouke B, Kusters DM, Kindt I, et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype–phenotype relationship, and clinical outcome. Eur Heart J. 2015;36:560–565.
doi: 10.1093/eurheartj/ehu058
Degoma EM, Ahmad ZS, O’Brien EC, et al. Treatment gaps in adults with heterozygous familial hypercholesterolemia in the United States. Circ Cardiovasc Genet. 2016;9:240–249.
doi: 10.1161/CIRCGENETICS.116.001381
Krogh HW, Mundal L, Holven KB, Retterstøl K. Patients with familial hypercholesterolaemia are characterized by presence of cardiovascular disease at the time of death. Eur Heart J. 2016;37:1398–1405.
doi: 10.1093/eurheartj/ehv602
Perak AM, Ning H, de Ferranti SD, Gooding HC, Wilkins JT, Lloyd-Jones DM. Long-term risk of atherosclerotic cardiovascular disease in US adults with the familial hypercholesterolemia phenotype. Circulation. 2016;134:9–19.
doi: 10.1161/CIRCULATIONAHA.116.022335
Tan GD, Neville MJ, Liverani E, et al. The in vivo effects of the Pro12Ala PPARγ2 polymorphism on adipose tissue NEFA metabolism: the first use of the Oxford Biobank. Diabetologia. 2006;49:158–168.
doi: 10.1007/s00125-005-0044-z
Tuomi T, Nagorny CLF, Singh P, et al. Increased melatonin signaling is a risk factor for type 2 diabetes. Cell Metab. 2016;23:1067–1077.
doi: 10.1016/j.cmet.2016.04.009
A.W U-EM, Defesche JC, Sijbrands EJG, Scheerder RLJM, Kastelein JJP. Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands. Lancet. 2001;357:165–168.
doi: 10.1016/S0140-6736(00)03587-X
Kerr M, Pears R, Miedzybrodzka Z, et al. Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK. Eur Heart J. 2017;38:1832–1839.
doi: 10.1093/eurheartj/ehx111
Lázaro P, Pérez de Isla L, Watts GF, et al. Cost-effectiveness of a cascade screening program for the early detection of familial hypercholesterolemia. J Clin Lipidol. 2017;11:260–271.
doi: 10.1016/j.jacl.2017.01.002
Leigh S, Futema M, Whittall R, et al. The UCL low-density lipoprotein receptor gene variant database: pathogenicity update. J Med Genet. 2017;54:217 LP–217223.
doi: 10.1136/jmedgenet-2016-104054
Goldmann R, Tichý L, Freiberger T, et al. Genomic characterization of large rearrangements of the LDLR gene in Czech patients with familial hypercholesterolemia. BMC Med Genet. 2010;11:115.
doi: 10.1186/1471-2350-11-115
Rehm HL, Berg JS, Brooks LD. et al. ClinGen—the Clinical Genome Resource. N Engl J Med. 2015;372:2235–2242.
doi: 10.1056/NEJMsr1406261