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Leif Groop

Leif Groop

Principal investigator

Leif Groop

The trans-ancestral genomic architecture of glycemic traits

Author

  • J. Chen
  • Valeriya Lyssenko
  • Paul Franks
  • Sölve Elmståhl
  • Leif Groop
  • C. van Duijn

Summary, in English

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Genetic and Molecular Epidemiology
  • Geriatrics

Publishing year

2021

Language

English

Pages

840-860

Publication/Series

Nature Genetics

Volume

53

Issue

6

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Keywords

  • glycosylated hemoglobin
  • allele
  • Caucasian
  • chromosomal mapping
  • gene expression profiling
  • genetic epigenesis
  • genetics
  • genome-wide association study
  • glucose blood level
  • human
  • human genome
  • metabolism
  • multifactorial inheritance
  • quantitative trait
  • quantitative trait locus
  • Alleles
  • Blood Glucose
  • Epigenesis, Genetic
  • European Continental Ancestry Group
  • Gene Expression Profiling
  • Genome, Human
  • Genome-Wide Association Study
  • Glycated Hemoglobin A
  • Humans
  • Multifactorial Inheritance
  • Physical Chromosome Mapping
  • Quantitative Trait Loci
  • Quantitative Trait, Heritable

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Genetic and Molecular Epidemiology
  • Geriatrics

ISBN/ISSN/Other

  • ISSN: 1546-1718