| Title: | A cross-platform approach identifies genetic regulators of human metabolism and health |
| Journal: | Nature Genetics |
| Published: | 7 Jan 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33414548/ |
| DOI: | https://doi.org/10.1038/s41588-020-00751-5 |
| URL: | https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=60943 |
| Citations: | 122 (60 in last 2 years) as of 8 Aug 2024 |
Publication 9532
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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.</p>
21 Keywords
- Diabetes Mellitus, Type 2
- Eye Diseases
- Gene Frequency
- Genetic Loci
- Genetic Pleiotropy
- Genome, Human
- Glucagon-Like Peptide-2 Receptor
- Glycine
- Health
- Humans
- Linear Models
- Mendelian Randomization Analysis
- Metabolism
- Metabolism, Inborn Errors
- Metabolome
- Mutation, Missense
- Phenotype
- Polymorphism, Single Nucleotide
- Retinal Telangiectasis
- Sample Size
- Serine
34 Authors
- Luca A. Lotta
- Maik Pietzner
- Isobel D. Stewart
- Laura B. L. Wittemans
- Chen Li
- Roberto Bonelli
- Johannes Raffler
- Emma K. Biggs
- Clare Oliver-Williams
- Victoria P. W. Auyeung
- Jian'an Luan
- Eleanor Wheeler
- Ellie Paige
- Praveen Surendran
- Gregory A. Michelotti
- Robert A. Scott
- Stephen Burgess
- Verena Zuber
- Eleanor Sanderson
- Albert Koulman
- Fumiaki Imamura
- Nita G. Forouhi
- Kay-Tee Khaw
- Julian L. Griffin
- Angela M. Wood
- Gabi Kastenmüller
- John Danesh
- Adam S. Butterworth
- Fiona M. Gribble
- Frank Reimann
- Melanie Bahlo
- Eric Fauman
- Nicholas J. Wareham
- Claudia Langenberg
1 Application
| Application ID | Title |
|---|---|
| 44448 | The genetic and environmental determinants of cardiometabolic and related disorders. |
Enabling scientific discoveries that improve human health