原创力文档a three-stage approach for genome-wide association studies with family data for quantitative traits一个三级全基因组关联研究方法与家人数据量化特征.pdfVIP
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a three-stage approach for genome-wide association studies with family data for quantitative traits一个三级全基因组关联研究方法与家人数据量化特征
Chen et al. BMC Genetics 2010, 11:40
/1471-2156/11/40
R E S E A R C H A R T I C L E Open Access
Research article
A three-stage approach for genome-wide
association studies with family data for
quantitative traits
1 2,3 4,5 6 7,8,9 10
Ming-Huei Chen , Martin G Larson , Yi-Hsiang Hsu , Gina M Peloso , Chao-Yu Guo , Caroline S Fox ,
1,2 6
Larry D Atwood and Qiong Yang*
Abstract
Background: Genome-wide association (GWA) studies that use population-based association approaches may identify
spurious associations in the presence of population admixture. In this paper, we propose a novel three-stage approach
that is computationally efficient and robust to population admixture and more powerful than the family-based
association test (FBAT) for GWA studies with family data.
We propose a three-stage approach for GWA studies with family data. The first stage is to perform linear regression
ignoring phenotypic correlations among family members. SNPs with a first stage p-value below a liberal cut-off (e.g.
0.1) are then analyzed in the second stage that employs a linear mixed effects (LME) model that accounts for within
family correlations. Next, SNPs that reach genome-wide significance (e.g. 10-6 for 34,625 genotyped SNPs in this paper)
are analyzed in the third stage using FBAT, with correction of multiple testing only for SNPs that enter the third stage.
Simulations are performed to evaluate type I error and power of the proposed method compared to LME adjusting for
10 principal components (PC) of the genotype data. We also apply the three-stage approach to the GWA analyses of
uric acid in Framingham Heart Studys SNP Health Association Resource
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