A Permutation Procedure to Correct for Confounders in Case-Control Studies, Including Tests of Rare Variation

被引:56
作者
Epstein, Michael P. [1 ]
Duncan, Richard [1 ]
Jiang, Yunxuan [2 ]
Conneely, Karen N. [1 ]
Allen, Andrew S. [3 ]
Satten, Glen A. [4 ]
机构
[1] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA
[2] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA
[3] Duke Univ, Dept Biostat & Bioinformat, Durham, NC 27710 USA
[4] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA
基金
美国国家卫生研究院;
关键词
WHOLE-GENOME ASSOCIATION; POPULATION STRATIFICATION; GENETIC-ASSOCIATION; DISEASE VARIANTS; COMMON DISEASES; SEQUENCE DATA; STRATEGIES; DISORDERS; MAP;
D O I
10.1016/j.ajhg.2012.06.004
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Many case-control tests of rare variation are implemented in statistical frameworks that make correction for confounders like population stratification difficult. Simple permutation of disease status is unacceptable for resolving this issue because the replicate data sets do not have the same confounding as the original data set. These limitations make it difficult to apply rare-variant tests to samples in which confounding most likely exists, e.g., samples collected from admixed populations. To enable the use of such rare-variant methods in structured samples, as well as to facilitate permutation tests for any situation in which case-control tests require adjustment for confounding covariates, we propose to establish the significance of a rare-variant test via a modified permutation procedure. Our procedure uses Fisher's noncentral hypergeometric distribution to generate permuted data sets with the same structure present in the actual data set such that inference is valid in the presence of confounding factors. We use simulated sequence data based on coalescent models to show that our permutation strategy corrects for confounding due to population stratification that, if ignored, would otherwise inflate the size of a rare-variant test. We further illustrate the approach by using sequence data from the Dallas Heart Study of energy metabolism traits. Researchers can implement our permutation approach by using the R package BiasedUrn.
引用
收藏
页码:215 / 223
页数:9
相关论文
共 41 条
  • [1] Score-based Adjustment for Confounding by Population Stratification in Genetic Association Studies
    Allen, Andrew
    Epstein, Michael P.
    Satten, Glen A.
    [J]. GENETIC EPIDEMIOLOGY, 2010, 34 (05) : 383 - 385
  • [2] A map of human genome variation from population-scale sequencing
    Altshuler, David
    Durbin, Richard M.
    Abecasis, Goncalo R.
    Bentley, David R.
    Chakravarti, Aravinda
    Clark, Andrew G.
    Collins, Francis S.
    De la Vega, Francisco M.
    Donnelly, Peter
    Egholm, Michael
    Flicek, Paul
    Gabriel, Stacey B.
    Gibbs, Richard A.
    Knoppers, Bartha M.
    Lander, Eric S.
    Lehrach, Hans
    Mardis, Elaine R.
    McVean, Gil A.
    Nickerson, DebbieA.
    Peltonen, Leena
    Schafer, Alan J.
    Sherry, Stephen T.
    Wang, Jun
    Wilson, Richard K.
    Gibbs, Richard A.
    Deiros, David
    Metzker, Mike
    Muzny, Donna
    Reid, Jeff
    Wheeler, David
    Wang, Jun
    Li, Jingxiang
    Jian, Min
    Li, Guoqing
    Li, Ruiqiang
    Liang, Huiqing
    Tian, Geng
    Wang, Bo
    Wang, Jian
    Wang, Wei
    Yang, Huanming
    Zhang, Xiuqing
    Zheng, Huisong
    Lander, Eric S.
    Altshuler, David L.
    Ambrogio, Lauren
    Bloom, Toby
    Cibulskis, Kristian
    Fennell, Tim J.
    Gabriel, Stacey B.
    [J]. NATURE, 2010, 467 (7319) : 1061 - 1073
  • [3] [Anonymous], 1993, An introduction to the bootstrap
  • [4] Statistical analysis strategies for association studies involving rare variants
    Bansal, Vikas
    Libiger, Ondrej
    Torkamani, Ali
    Schork, Nicholas J.
    [J]. NATURE REVIEWS GENETICS, 2010, 11 (11) : 773 - 785
  • [5] Qualitative semi-parametric test for genetic associations in case-control designs under structured populations
    Chen, HS
    Zhu, X
    Zhao, H
    Zhang, S
    [J]. ANNALS OF HUMAN GENETICS, 2003, 67 : 250 - 264
  • [6] BOOTSTRAP CONFIDENCE-INTERVALS FOR A CLASS OF PARAMETRIC PROBLEMS
    EFRON, B
    [J]. BIOMETRIKA, 1985, 72 (01) : 45 - 58
  • [7] A simple and improved correction for population stratification in case-control studies
    Epstein, Michael P.
    Allen, Andrew S.
    Satten, Glen A.
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (05) : 921 - 930
  • [8] A whole-genome association study of major determinants for host control of HIV-1
    Fellay, Jacques
    Shianna, Kevin V.
    Ge, Dongliang
    Colombo, Sara
    Ledergerber, Bruno
    Weale, Mike
    Zhang, Kunlin
    Gumbs, Curtis
    Castagna, Antonella
    Cossarizza, Andrea
    Cozzi-Lepri, Alessandro
    De Luca, Andrea
    Easterbrook, Philippa
    Francioli, Patrick
    Mallal, Simon
    Martinez-Picado, Javier
    Miro, Jose M.
    Obel, Niels
    Smith, Jason P.
    Wyniger, Josiane
    Descombes, Patrick
    Antonarakis, Stylianos E.
    Letvin, Norman L.
    McMichael, Andrew J.
    Haynes, Barton F.
    Telenti, Amalio
    Goldstein, David B.
    [J]. SCIENCE, 2007, 317 (5840) : 944 - 947
  • [9] Fog A., 2011, BIASEDURN BIASED URN
  • [10] Sampling methods for Wallenius' and Fisher's noncentral hypergeometric distributions
    Fog, Agner
    [J]. COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION, 2008, 37 (02) : 241 - 257