RT Journal Article
SR Electronic
T1 Components of genetic associations across 2,138 phenotypes in the UK Biobank highlight novel adipocyte biology
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 442715
DO 10.1101/442715
A1 Yosuke Tanigawa
A1 Jiehan Li
A1 Johanne Marie Justesen
A1 Heiko Horn
A1 Matthew Aguirre
A1 Christopher DeBoever
A1 Chris Chang
A1 Balasubramanian Narasimhan
A1 Kasper Lage
A1 Trevor Hastie
A1 Chong Yon Park
A1 Gill Bejerano
A1 Erik Ingelsson
A1 Manuel A. Rivas
YR 2019
UL http://biorxiv.org/content/early/2019/03/19/442715.abstract
AB Population-based biobanks with genomic and dense phenotype data provide opportunities for generating effective therapeutic hypotheses and understanding the genomic role in disease predisposition. To characterize latent components of genetic associations, we applied truncated singular value decomposition (DeGAs) to matrices of summary statistics derived from genome-wide association analyses across 2,138 phenotypes measured in 337,199 White British individuals in the UK Biobank study. We systematically identified key components of genetic associations and the contributions of variants, genes, and phenotypes to each component. As an illustration of the utility of the approach to inform downstream experiments, we report putative loss of function variants, rs114285050 (GPR151) and rs150090666 (PDE3B), that substantially contribute to obesity-related traits, and experimentally demonstrate the role of these genes in adipocyte biology. Our approach to dissect components of genetic associations across the human phenome will accelerate biomedical hypothesis generation by providing insights on previously unexplored latent structures.