Physical Sciences and Mathematics Commons^™

Meta-Analysis Of Genome-Wide Association Studies With Correlated Individuals: Application To The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Tamar Sofer, John R. Shaffer, Misa Graff, Qibin Qi, Adrienne M. Stilp, Stephanie M. Gogarten, Kari E. North, Carmen R. Isasi, Cathy C. Laurie, Adam A. Szpiro

UW Biostatistics Working Paper Series

Investigators often meta-analyze multiple genome-wide association studies (GWASs) to increase the power to detect associations of single nucleotide polymorphisms (SNPs) with a trait. Meta-analysis is also performed within a single cohort that is stratified by, e.g., sex or ancestry group. Having correlated individuals among the strata may complicate meta-analyses, limit power, and inflate Type 1 error. For example, in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), sources of correlation include genetic relatedness, shared household, and shared community. We propose a novel mixed-effect model for meta-analysis, “MetaCor", which accounts for correlation between stratum-specific effect estimates. Simulations show that MetaCor controls …