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Lotta, Luca A; Pietzner, Maik; Stewart, Isobel D; Wittemans, Laura B L; Li, Chen; Bonelli, Roberto; Raffler, Johannes; Biggs, Emma K; Oliver-Williams, Clare; Auyeung, Victoria P W; Luan, Jian'an; Wheeler, Eleanor; Paige, Ellie; Surendran, Praveen; Michelotti, Gregory A; Scott, Robert A; Burgess, Stephen; Zuber, Verena; Sanderson, Eleanor; Koulman, Albert; Imamura, Fumiaki; Forouhi, Nita G; Khaw, Kay-Tee; Griffin, Julian L; Wood, Angela M; Kastenmüller, Gabi; Danesh, John; Butterworth, Adam S; Gribble, Fiona M; Reimann, Frank; Bahlo, Melanie; Fauman, Eric; Wareham, Nicholas J; Langenberg, Claudia
Nature genetics, 01/2021, Letnik: 53, Številka: 1Journal Article
In cross-platform analyses of 174 metabolites, we identify 499 associations (P < 4.9 × 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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