Cross-ancestry and sex-stratified genome-wide association analyses of brain white matter principal components
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
White matter microstructure determines effective communications across brain regions, which can be better characterized by tract-specific principal components from diffusion tensor imaging data. Although genome-wide associations with tract-specific principal components are investigated in sex-combined individuals of European ancestry, cross-ancestry and sex-stratified analyses are lacking. We conducted both sex-combined and sex-stratified ancestry-specific and cross-ancestry genome-wide association studies for 525 tract-specific principal components in 7,003 Chinese Han and 33,908 White British individuals. We identified 1,844 variant-phenotype associations ( P < 9.52 × 10 -11 ), including 970 new, 47 ancestry-specific, and five sex-specific associations. The variants included 1,760 causal variants and enriched for biological processes related to axon and neuron development. White matter phenotypes were affected by both fetal and adult gene expression and colocalized with 32 brain-related non-imaging phenotypes, such as cognition, personality, schizophrenia, depression, Alzheimer’s disease, and multiple sclerosis. These findings may provide mechanistic insights into the genetic architecture of white matter microstructure.
