The genetic architecture of type 2 diabetes

Collapse authors list.
Fuchsberger, Christian, Flannick, Jason, Teslovich, Tanya M, Mahajan, Anubha, Agarwala, Vineeta, Gaulton, Kyle J, Ma, Clement, Fontanillas, Pierre, Moutsianas, Loukas, McCarthy, Davis J et al (show 291 more authors) (2016) The genetic architecture of type 2 diabetes. NATURE, 536 (7614). 41-+. ISSN 0028-0836, 1476-4687

	Spreadsheet 20Supp20_T2D loci and genes.xlsx - Author Accepted Manuscript Download (79kB)
	Text 2015-02-02237C_9June16.docx - Author Accepted Manuscript Download (1MB)
	Image Extended Display Figure 1.jpg - Author Accepted Manuscript Download (1MB)
	Image Extended Display Figure 4.jpg - Author Accepted Manuscript Download (1MB)
	Image Extended Display Figure 6.jpg - Author Accepted Manuscript Download (929kB)
	Image Extended Display Figure 7.jpg - Author Accepted Manuscript Download (1MB)
	Image Extended Display Figure 9.jpg - Author Accepted Manuscript Download (541kB)
	Image Extended Display Figure 10.jpg - Author Accepted Manuscript Download (1MB)
	Image Extended Display Figure 11.jpg - Author Accepted Manuscript Download (1MB)
	Image Extended Display Table 2.jpg - Author Accepted Manuscript Download (1MB)
	Image Extended Display Table 3.jpg - Author Accepted Manuscript Download (1MB)
	Image Extended Display Table 5.jpg - Author Accepted Manuscript Download (1MB)
	Image Extended Display Table 8.jpg - Author Accepted Manuscript Download (762kB)
	Text Figure1.pdf - Author Accepted Manuscript Download (572kB)
	Text Figure2.pdf - Author Accepted Manuscript Download (46kB)
	Text Figure3.pdf - Author Accepted Manuscript Download (382kB)
	Text Supplementary_Info.pdf - Author Accepted Manuscript Download (16MB)
	Atom XML (admin) 2017-05-12T11:17:15Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T12:16:37Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T13:16:14Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T14:16:08Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T15:16:19Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T16:16:21Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T17:16:04Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T18:16:25Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T19:16:16Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T20:16:20Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T21:16:34Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T22:16:28Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-12T23:21:42Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-13T01:16:54Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-13T02:16:43Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-13T03:16:47Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-13T04:30:13Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-13T05:16:38Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-13T06:16:18Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-13T07:16:28Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-13T08:16:41Z.atom - Unspecified Download (0B)
	Atom XML (admin) 2017-05-13T09:16:21Z.atom - Unspecified Download (0B)

Official URL: https://doi.org/10.1038/nature18642

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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Sample Size, DNA Mutational Analysis, Alleles, Europe, Genetic Variation, Genome-Wide Association Study, Genotyping Techniques, Exome
Depositing User:	Symplectic Admin
Date Deposited:	22 Jul 2016 13:59
Last Modified:	07 Dec 2024 17:02
DOI:	10.1038/nature18642
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3002481