中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
A robust and powerful two-step testing procedure for local ancestry adjusted allelic association analysis in admixed populations

文献类型:期刊论文

作者Duan, Qing1,2,3; Xu, Zheng1,4,5,7,8; Raffield, Laura M.1; Chang, Suhua9; Wu, Di4,6; Lange, Ethan M.10,11; Reiner, Alex P.12,13; Li, Yun1,2,4,5
刊名GENETIC EPIDEMIOLOGY
出版日期2018-04-01
卷号42期号:3页码:288-302
ISSN号0741-0395
关键词Admixed Populations Association Analysis Effect Heterogeneity Genome-wide Association Studies Gwas Local Ancestry Population Stratification Testing Procedure
DOI10.1002/gepi.22104
产权排序9
文献子类Article
英文摘要

Genetic association studies in admixed populations allow us to gain deeper understanding of the genetic architecture of human diseases and traits. However, population stratification, complicated linkage disequilibrium (LD) patterns, and the complex interplay of allelic and ancestry effects on phenotypic traits pose challenges in such analyses. These issues may lead to detecting spurious associations and/or result in reduced statistical power. Fortunately, if handled appropriately, these same challenges provide unique opportunities for gene mapping. To address these challenges and to take these opportunities, we propose a robust and powerful two-step testing procedure Local Ancestry Adjusted Allelic (LAAA) association. In the first step, LAAA robustly captures associations due to allelic effect, ancestry effect, and interaction effect, allowing detection of effect heterogeneity across ancestral populations. In the second step, LAAA identifies the source of association, namely allelic, ancestry, or the combination. By jointly modeling allele, local ancestry, and ancestry-specific allelic effects, LAAA is highly powerful in capturing the presence of interaction between ancestry and allele effect. We evaluated the validity and statistical power of LAAA through simulations over a broad spectrum of scenarios. We further illustrated its usefulness by application to the Candidate Gene Association Resource (CARe) African American participants for association with hemoglobin levels. We were able to replicate independent groups' previously identified loci that would have been missed in CARe without joint testing. Moreover, the loci, for which LAAA detected potential effect heterogeneity, were replicated among African Americans from the Women's Health Initiative study. LAAA is freely available at . https://yunliweb.its.unc.edu/LAAA.

WOS关键词GENOME-WIDE ASSOCIATION ; BLOOD-CELL TRAITS ; GENETIC ASSOCIATION ; AFRICAN-AMERICANS ; VARIANTS ; ADMIXTURE ; INFERENCE ; DESIGN ; STRATIFICATION ; HETEROGENEITY
WOS研究方向Genetics & Heredity ; Mathematical & Computational Biology
语种英语
WOS记录号WOS:000427473900005
资助机构National Human Genome Research Institute(R01HG006292 ; National Heart, Lung, and Blood Institute(R01HL129132 ; R01HG006703) ; R21HL126045)
源URL[http://ir.psych.ac.cn/handle/311026/26055]  
专题心理研究所_中国科学院心理健康重点实验室
作者单位1.Univ N Carolina, Dept Genet, Campus Box 7264, Chapel Hill, NC 27599 USA
2.Univ N Carolina, Curriculum Bioinformat & Computat Biol, Chapel Hill, NC USA
3.Univ N Carolina, Dept Stat, Chapel Hill, NC USA
4.Univ N Carolina, Dept Biostat, Chapel Hill, NC USA
5.Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA
6.Univ N Carolina, Dept Periodontol, Chapel Hill, NC USA
7.Univ Nebraska, Dept Stat, Lincoln, NE USA
8.Univ Nebraska, Initiat Quantitat Life Sci, Lincoln, NE USA
9.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China
10.Univ Colorado, Dept Med, Anschutz Med Campus, Denver, CO USA
推荐引用方式
GB/T 7714
Duan, Qing,Xu, Zheng,Raffield, Laura M.,et al. A robust and powerful two-step testing procedure for local ancestry adjusted allelic association analysis in admixed populations[J]. GENETIC EPIDEMIOLOGY,2018,42(3):288-302.
APA Duan, Qing.,Xu, Zheng.,Raffield, Laura M..,Chang, Suhua.,Wu, Di.,...&Li, Yun.(2018).A robust and powerful two-step testing procedure for local ancestry adjusted allelic association analysis in admixed populations.GENETIC EPIDEMIOLOGY,42(3),288-302.
MLA Duan, Qing,et al."A robust and powerful two-step testing procedure for local ancestry adjusted allelic association analysis in admixed populations".GENETIC EPIDEMIOLOGY 42.3(2018):288-302.

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来源:心理研究所

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