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Genetic determinants of lipid traits in diverse populations from the population Architecture using Genomics and Epidemiology (PAGE) study
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نویسنده
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dumitrescu l. ,carty c.l. ,taylor k. ,schumacher f.r. ,hindorff l.a. ,ambite j.l. ,anderson g. ,best l.g. ,brown-gentry k. ,bůžková p. ,carlson c.s. ,cochran b. ,cole s.a. ,devereux r.b. ,duggan d. ,eaton c.b. ,fornage m. ,franceschini n. ,haessler j. ,howard b.v. ,johnson k.c. ,laston s. ,kolonel l.n. ,lee e.t. ,maccluer j.w. ,manolio t.a. ,pendergrass s.a. ,quibrera m. ,shohet r.v. ,wilkens l.r. ,haiman c.a. ,le marchand l. ,buyske s. ,kooperberg c. ,north k.e. ,crawford d.c.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 6
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چکیده
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For the past five years,genome-wide association studies (gwas) have identified hundreds of common variants associated with human diseases and traits,including high-density lipoprotein cholesterol (hdl-c),low-density lipoprotein cholesterol (ldl-c),and triglyceride (tg) levels. approximately 95 loci associated with lipid levels have been identified primarily among populations of european ancestry. the population architecture using genomics and epidemiology (page) study was established in 2008 to characterize gwas-identified variants in diverse population-based studies. we genotyped 49 gwas-identified snps associated with one or more lipid traits in at least two page studies and across six racial/ethnic groups. we performed a meta-analysis testing for snp associations with fasting hdl-c,ldl-c,and ln(tg) levels in self-identified european american (~20,000),african american (~9,000),american indian (~6,000),mexican american/hispanic (~2,500),japanese/east asian (~690),and pacific islander/native hawaiian (~175) adults,regardless of lipid-lowering medication use. we replicated 55 of 60 (92%) snp associations tested in european americans at p<0.05. despite sufficient power,we were unable to replicate abca1 rs4149268 and rs1883025,cetp rs1864163,and ttc39b rs471364 previously associated with hdl-c and mafb rs6102059 previously associated with ldl-c. based on significance (p<0.05) and consistent direction of effect,a majority of replicated genotype-phentoype associations for hdl-c,ldl-c,and ln(tg) in european americans generalized to african americans (48%,61%,and 57%),american indians (45%,64%,and 77%),and mexican americans/hispanics (57%,56%,and 86%). overall,16 associations generalized across all three populations. for the associations that did not generalize,differences in effect sizes,allele frequencies,and linkage disequilibrium offer clues to the next generation of association studies for these traits.
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آدرس
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center for human genetics research,vanderbilt university,nashville,tn, United States, public health sciences,fred hutchinson cancer research center,seattle,wa, United States, department of epidemiology,university of north carolina,chapel hill,nc, United States, department of preventive medicine,keck school of medicine,university of southern california,los angeles,ca, United States, office of population genomics,national human genome research institute,bethesda,md, United States, information sciences institute,university of southern california,los angeles,ca, United States, public health sciences,fred hutchinson cancer research center,seattle,wa, United States, missouri breaks industries research,timber lake,sd, United States, center for human genetics research,vanderbilt university,nashville,tn, United States, department of biostatistics,university of washington,seattle,wa, United States, public health sciences,fred hutchinson cancer research center,seattle,wa, United States, sponsored programs,baylor college of medicine,houston,tx, United States, department of genetics,southwest foundation for biomedical research,san antonio,tx, United States, department of medicine,weill cornell medical college,new york,ny, United States, the translational genomics research institute,phoenix,az, United States, department of family medicine and community health,alpert medical school of brown university school of medicine,providence,ri, United States, institute of molecular medicine,university of texas health sciences center at houston,texas,united states,division of epidemiology,school of public health,university of texas health sciences center,houston,tx, United States, department of epidemiology,university of north carolina,chapel hill,nc, United States, public health sciences,fred hutchinson cancer research center,seattle,wa, United States, medstar research institute,washington,dc, United States, department of preventive medicine,university of tennessee health science center,memphis,tn, United States, department of genetics,southwest foundation for biomedical research,san antonio,tx, United States, epidemiology program,university of hawaii cancer center,department of medicine,john a. burns school of medicine,university of hawaii,honolulu,hi, United States, university of oklahoma health sciences center,oklahoma city,ok, United States, department of genetics,southwest foundation for biomedical research,san antonio,tx, United States, office of population genomics,national human genome research institute,bethesda,md, United States, center for human genetics research,vanderbilt university,nashville,tn, United States, school of public health,university of north carolina,chapel hill,nc, United States, center of cardiovascular research,department of medicine,john a. burns school of medicine,university of hawaii,honolulu,hi, United States, epidemiology program,university of hawaii cancer center,department of medicine,john a. burns school of medicine,university of hawaii,honolulu,hi, United States, department of preventive medicine,keck school of medicine,university of southern california,los angeles,ca, United States, epidemiology program,university of hawaii cancer center,department of medicine,john a. burns school of medicine,university of hawaii,honolulu,hi, United States, department of statistics and biostatistics,rutgers university,piscataway,nj, United States, public health sciences,fred hutchinson cancer research center,seattle,wa, United States, department of epidemiology,university of north carolina,chapel hill,nc,united states,carolina center for genome sciences,university of north carolina,chapel hill,nc, United States, center for human genetics research,vanderbilt university,nashville,tn,united states,department of molecular physiology and biophysics,vanderbilt university,nashville,tn, United States
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Authors
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