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Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium.

Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
TitleEnhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium.
Publication TypeJournal Article
Year of Publication2011
AuthorsPasaniuc, B, Zaitlen, N, Lettre, G, Chen, GK, Tandon, A, Kao, LWH, Ruczinski, I, Fornage, M, Siscovick, DS, Zhu, X, Larkin, E, Lange, LA, Cupples, AL, Yang, Q, Akylbekova, EL, Musani, SK, Divers, J, Mychaleckyj, J, Li, M, Papanicolaou, GJ, Millikan, RC, Ambrosone, CB, John, EM, Bernstein, L, Zheng, W, Hu, JJ, Ziegler, RG, Nyante, SJ, Bandera, EV, Ingles, SA, Press, MF, Chanock, SJ, Deming, SL, Rodriguez-Gil, JL, Palmer, CD, Buxbaum, S, Ekunwe, L, Hirschhorn, JN, Henderson, BE, Myers, S, Haiman, CA, Reich, D, Patterson, N, Wilson, JG, Price, AL
JournalPLoS Genet
Volume7
Issue4
Paginatione1001371
Date Published2011 Apr
ISSN1553-7404
KeywordsAfrican Americans, Algorithms, Breast Neoplasms, Chromosome Mapping, Coronary Disease, Diabetes Mellitus, Type 2, Female, Gene Frequency, Genetic Variation, Genetics, Population, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Linkage Disequilibrium, Male, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Principal Component Analysis, Receptor, Fibroblast Growth Factor, Type 2, Software
Abstract<p>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.</p>
DOI10.1371/journal.pgen.1001371
Alternate JournalPLoS Genet.
PubMed ID21541012
PubMed Central IDPMC3080860
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
U01 CA069417 / CA / NCI NIH HHS / United States
N01-HB-72992 / HB / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N01-HB-97068 / HB / NHLBI NIH HHS / United States
N01-HB-97053 / HB / NHLBI NIH HHS / United States
N01-HB-72997 / HB / NHLBI NIH HHS / United States
N01-HB-73003 / HB / NHLBI NIH HHS / United States
K99 CA126978 / CA / NCI NIH HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
R01-CA73629 / CA / NCI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
N01-HC-9518 / HC / NHLBI NIH HHS / United States
5K99CA126978-02 / CA / NCI NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
N01-HC-55017 / HC / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
U01 HL053916 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01 HL046380 / HL / NHLBI NIH HHS / United States
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U01 HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
U01 HL063463 / HL / NHLBI NIH HHS / United States
N01-HB-97064 / HB / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
RC1 GM091332 / GM / NIGMS NIH HHS / United States
T32 ES007142 / ES / NIEHS NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
N01HC45205 / HL / NHLBI NIH HHS / United States
R01-CA63464 / CA / NCI NIH HHS / United States
5T32ES007142-27 / ES / NIEHS NIH HHS / United States
N01-HC-95163 / HC / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
U01-CA69417 / CA / NCI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R01 CA073629 / CA / NCI NIH HHS / United States
N01-HB-73002 / HB / NHLBI NIH HHS / United States
N01-HC-45204 / HC / NHLBI NIH HHS / United States
N01-HB-72993 / HB / NHLBI NIH HHS / United States
N01-HB-97070 / HB / NHLBI NIH HHS / United States
N01-HC-9517 / HC / NHLBI NIH HHS / United States
R01 HG006399 / HG / NHGRI NIH HHS / United States
N01-HB-97056 / HB / NHLBI NIH HHS / United States
N01-HB-72982 / HB / NHLBI NIH HHS / United States
R01-CA100598 / CA / NCI NIH HHS / United States
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HHSN268200960009C / / PHS HHS / United States
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U01 HL064363 / HL / NHLBI NIH HHS / United States
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090532 / / Wellcome Trust / United Kingdom
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R37 CA054281 / CA / NCI NIH HHS / United States
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