The genetic architecture of type 2 diabetes
Name
nihms-795012.pdf
Size
2.45 MB
Format
Adobe PDF
Checksum (MD5)
e327ce7d98d240ae8a3463ccf7712e6b
Author(s)
Altshuler, David
Date Issued
August 2016
Journal
Nature
Publisher
Nature Publishing Group
Citation
Fuchsberger, Christian et al. “The Genetic Architecture of Type 2 Diabetes.” Nature 536, 7614 (July 2016): 41–47 © 2016 Macmillan Publishers Limited, part of Springer Nature
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/NATURE18642
