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Enhanced statistical tests for GWAS in admixed populations: Assessment using african americans from CARe and a breast cancer consortium
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نویسنده
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pasaniuc b. ,zaitlen n. ,lettre g. ,chen g.k. ,tandon a. ,kao w.h.l. ,ruczinski i. ,fornage m. ,siscovick d.s. ,zhu x. ,larkin e. ,lange l.a. ,cupples l.a. ,yang q. ,akylbekova e.l. ,musani s.k. ,divers j. ,mychaleckyj j. ,li m. ,papanicolaou g.j. ,millikan r.c. ,ambrosone c.b. ,john e.m. ,bernstein l. ,zheng w. ,hu j.j. ,ziegler r.g. ,nyante s.j. ,bandera e.v. ,ingles s.a. ,press m.f. ,chanock s.j. ,deming s.l. ,rodriguez-gil j.l. ,palmer c.d. ,buxbaum s. ,ekunwe l. ,hirschhorn j.n. ,henderson b.e. ,myers s. ,haiman c.a. ,reich d. ,patterson n. ,wilson j.g. ,price a.l.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 4
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چکیده
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While genome-wide association studies (gwas) have primarily examined populations of european ancestry,more recent studies often involve additional populations,including admixed populations such as african americans and latinos. in admixed populations,linkage disequilibrium (ld) exists both at a fine scale in ancestral populations and at a coarse scale (admixture-ld) due to chromosomal segments of distinct ancestry. disease association statistics in admixed populations have previously considered snp association (ld mapping) or admixture association (mapping by admixture-ld),but not both. here,we introduce a new statistical framework for combining snp and admixture association in case-control studies,as well as methods for local ancestry-aware imputation. we illustrate the gain in statistical power achieved by these methods by analyzing data of 6,209 unrelated african americans from the care project genotyped on the affymetrix 6.0 chip,in conjunction with both simulated and real phenotypes,as well as by analyzing the fgfr2 locus using breast cancer gwas data from 5,761 african-american women. we show that,at typed snps,our method yields an 8% increase in statistical power for finding disease risk loci compared to the power achieved by standard methods in case-control studies. at imputed snps,we observe an 11% increase in statistical power for mapping disease loci when our local ancestry-aware imputation framework and the new scoring statistic are jointly employed. finally,we show that our method increases statistical power in regions harboring the causal snp in the case when the causal snp is untyped and cannot be imputed. our methods and our publicly available software are broadly applicable to gwas in admixed populations.
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آدرس
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department of epidemiology,harvard school of public health,boston,ma,united states,department of biostatistics,harvard school of public health,boston,ma,united states,broad institute of harvard and massachusetts institute of technology (mit),cambridge,ma, United States, department of epidemiology,harvard school of public health,boston,ma,united states,department of biostatistics,harvard school of public health,boston,ma,united states,broad institute of harvard and massachusetts institute of technology (mit),cambridge,ma, United States, montreal heart institute,montréal,canada,département de médecine,université de montréal,montréal, Canada, department of preventive medicine,university of southern california keck school of medicine,los angeles,ca, United States, broad institute of harvard and massachusetts institute of technology (mit),cambridge,ma,united states,department of genetics,harvard medical school,boston,ma, United States, department of epidemiology,johns hopkins university,baltimore,md,united states,welch center for prevention,epidemiology and clinical research,johns hopkins university,baltimore,md, United States, department of biostatistics,bloomberg school of public health,johns hopkins university,baltimore,md, United States, institute of molecular medicine and division of epidemiology,school of public health,university of texas health sciences center at houston,houston,tx, United States, departments of medicine and epidemiology,university of washington,seattle,wa,united states,cardiovascular health research unit,university of washington,seattle,wa, United States, department of epidemiology and biostatistics,school of medicine,case western reserve university,cleveland,oh, United States, department of medicine,division of allergy,pulmonary and critical care,vanderbilt university,nashville,tn, United States, department of genetics,university of north carolina,chapel hill,nc, United States, department of biostatistics and epidemiology,boston university school of public health,boston,ma, United States, department of biostatistics and epidemiology,boston university school of public health,boston,ma, United States, jackson heart study,jackson state university,jackson,ms, United States, university of mississippi medical center,jackson,ms, United States, department of biostatistical sciences,division of public health sciences,wake forest university,winston-salem,nc, United States, center for public health genomics,university of virginia,charlottesville,va, United States, department of biostatistics and epidemiology,university of pennsylvania,philadelphia,pa, United States, national heart,lung,and blood institute (nhlbi),division of cardiovascular sciences,national institutes of health,bethesda,md, United States, department of epidemiology,gillings school of global public health,chapel hill,nc,united states,lineberger comprehensive cancer center,university of north carolina,chapel hill,nc, United States, department of cancer prevention and control,roswell park cancer institute,buffalo,ny, United States, northern california cancer center,fremont,ca,united states,stanford university school of medicine and stanford cancer center,stanford,ca, United States, division of cancer etiology,department of population science,beckman research institute,city of hope,ca, United States, division of epidemiology,department of medicine,vanderbilt epidemiology center,nashville,tn,united states,vanderbilt-ingram cancer center,vanderbilt university school of medicine,nashville,tn, United States, sylvester comprehensive cancer center and department of epidemiology and public health,university of miami miller school of medicine,miami,fl, United States, epidemiology and biostatistics program,division of cancer epidemiology and genetics,national cancer institute,bethesda,md, United States, lineberger comprehensive cancer center,university of north carolina,chapel hill,nc, United States, the cancer institute of new jersey,robert wood johnson medical school,new brunswick,nj, United States, department of preventive medicine,university of southern california keck school of medicine,los angeles,ca, United States, department of preventive medicine,university of southern california keck school of medicine,los angeles,ca, United States, division of cancer epidemiology and genetics,national cancer institute,bethesda,md, United States, institute for medicine and public health,vanderbilt epidemiology center,nashville,tn, United States, sylvester comprehensive cancer center and department of epidemiology and public health,university of miami miller school of medicine,miami,fl, United States, broad institute of harvard and massachusetts institute of technology (mit),cambridge,ma,united states,divisions of genetics and endocrinology and program in genomics,children's hospital boston,boston,ma, United States, jackson heart study,jackson state university,jackson,ms, United States, jackson heart study,jackson state university,jackson,ms, United States, broad institute of harvard and massachusetts institute of technology (mit),cambridge,ma,united states,department of genetics,harvard medical school,boston,ma,united states,divisions of genetics and endocrinology and program in genomics,children's hospital boston,boston,ma, United States, department of preventive medicine,university of southern california keck school of medicine,los angeles,ca, United States, department of statistics,university of oxford,oxford, United Kingdom, department of preventive medicine,university of southern california keck school of medicine,los angeles,ca, United States, broad institute of harvard and massachusetts institute of technology (mit),cambridge,ma,united states,department of genetics,harvard medical school,boston,ma, United States, broad institute of harvard and massachusetts institute of technology (mit),cambridge,ma, United States, university of mississippi medical center,jackson,ms,united states,v. a. medical center,jackson,ms, United States, department of epidemiology,harvard school of public health,boston,ma,united states,department of biostatistics,harvard school of public health,boston,ma,united states,broad institute of harvard and massachusetts institute of technology (mit),cambridge,ma, United States
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Authors
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