Detecting Rare Variants in Case-Parents Association Studies

Kuang Fu Cheng, Jin Hua Chen

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

Despite the success of genome-wide association studies (GWASs) in detecting common variants (minor allele frequency ≥0.05) many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common) variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT), multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

原文英語
文章編號e74310
期刊PLoS ONE
8
發行號9
DOIs
出版狀態已發佈 - 9月 26 2013

ASJC Scopus subject areas

  • 一般生物化學,遺傳學和分子生物學
  • 一般農業與生物科學
  • 多學科

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