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Paul Franks

Paul Franks

Principal investigator

Paul Franks

The genetic architecture of type 2 diabetes

Author

  • Christian Fuchsberger
  • Tibor V. Varga
  • Claes Ladenvall
  • Jasmina Kravic
  • Paul Franks
  • Valeriya Lyssenko
  • Anders Rosengren
  • Leif Groop
  • Olle Melander
  • Peter Nilsson
  • Mark I. McCarthy

Summary, in English

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes. © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Department/s

  • Genetic and Molecular Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Genomics, Diabetes and Endocrinology
  • Diabetic Complications
  • EpiHealth: Epidemiology for Health
  • Diabetes - Islet Patophysiology
  • Cardiovascular Research - Hypertension
  • Internal Medicine - Epidemiology

Publishing year

2016

Language

English

Pages

41-47

Publication/Series

Nature

Volume

536

Issue

7614

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Keywords

  • allele
  • ancestry
  • diabetes
  • genetic analysis
  • genetic structure
  • genome
  • health risk
  • pathology
  • physiology
  • Article
  • controlled study
  • European
  • exome
  • gene sequence
  • genetic code
  • genetic variation
  • genome-wide association study
  • genotype
  • human
  • major clinical study
  • non insulin dependent diabetes mellitus
  • priority journal
  • dna mutational analysis
  • ethnology
  • Europe
  • genetic predisposition
  • genetics
  • genotyping technique
  • sample size
  • Alleles
  • Diabetes Mellitus, Type 2
  • DNA Mutational Analysis
  • Exome
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Genotyping Techniques
  • Humans
  • Sample Size

Status

Published

Research group

  • Genetic and Molecular Epidemiology
  • Genomics, Diabetes and Endocrinology
  • Diabetic Complications
  • Diabetes - Islet Patophysiology
  • Cardiovascular Research - Hypertension
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 0028-0836