Total genetic contribution assessment across the human genome.
Ting LiZheng NingZhijian YangRanran ZhaiChenqing ZhengWenzheng XuYipeng WangAlbert K YingYiwen ChenXia ShenPublished in: Nature communications (2021)
Quantifying the overall magnitude of every single locus' genetic effect on the widely measured human phenome is of great challenge. We introduce a unified modelling technique that can consistently provide a total genetic contribution assessment (TGCA) of a gene or genetic variant without thresholding genetic association signals. Genome-wide TGCA in five UK Biobank phenotype domains highlights loci such as the HLA locus for medical conditions, the bone mineral density locus WNT16 for physical measures, and the skin tanning locus MC1R and smoking behaviour locus CHRNA3 for lifestyle. Tissue-specificity investigation reveals several tissues associated with total genetic contributions, including the brain tissues for mental health. Such associations are driven by tissue-specific gene expressions, which share genetic basis with the total genetic contributions. TGCA can provide a genome-wide atlas for the overall genetic contributions in each particular domain of human complex traits.
Keyphrases
- genome wide
- dna methylation
- copy number
- mental health
- endothelial cells
- bone mineral density
- gene expression
- physical activity
- metabolic syndrome
- genome wide association study
- stem cells
- cardiovascular disease
- healthcare
- multiple sclerosis
- postmenopausal women
- single cell
- body composition
- induced pluripotent stem cells
- smoking cessation
- transcription factor
- soft tissue