A cross-platform approach identifies genetic regulators of human metabolism and health
- Author(s)
- Lotta, LA; Pietzner, M; Stewart, ID; Wittemans, LBL; Li, C; Bonelli, R; Raffler, J; Biggs, EK; Oliver-Williams, C; Auyeung, VPW; Luan, J; Wheeler, E; Paige, E; Surendran, P; Michelotti, GA; Scott, RA; Burgess, S; Zuber, V; Sanderson, E; Koulman, A; Imamura, F; Forouhi, NG; Khaw, KT; Griffin, JL; Wood, AM; Kastenmüller, G; Danesh, J; Butterworth, AS; Gribble, FM; Reimann, F; Bahlo, M; Fauman, E; Wareham, NJ; Langenberg, C;
- Details
- Publication Year 2021-01,Volume 53,Issue #1,Page 54-64
- Journal Title
- Nature Genetics
- Abstract
- In cross-platform analyses of 174 metabolites, we identify 499 associations (P < 4.9 × 10(-10)) characterized by pleiotropy, allelic heterogeneity, large and nonlinear effects and enrichment for nonsynonymous variation. We identify a signal at GLP2R (p.Asp470Asn) shared among higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes, with β-arrestin signaling as the underlying mechanism. Genetically higher serine levels are shown to reduce the likelihood (by 95%) and predict development of macular telangiectasia type 2, a rare degenerative retinal disease. Integration of genomic and small molecule data across platforms enables the discovery of regulators of human metabolism and translation into clinical insights.
- Publisher
- NPG
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 33414548
- Publisher's Version
- https://doi.org/10.1038/s41588-020-00751-5
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-03-04 09:10:14
Last Modified: 2021-03-08 01:28:22