Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

TitleLarge-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.
Publication TypeJournal Article
Year of Publication2012
AuthorsScott RA, Lagou V, Welch RP, Wheeler E, Montasser ME, Luan J'an, Mägi R, Strawbridge RJ, Rehnberg E, Gustafsson S et al.
Corporate AuthorsDIAbetes Genetics Replication and Meta-analysis(DIAGRAM) Consortium
JournalNat Genet
Volume44
Issue9
Pagination991-1005
Date Published2012 Sep
ISSN1546-1718
KeywordsAdult, Animals, Blood Glucose, Fasting, Female, Gene Frequency, Genome-Wide Association Study, Humans, Insulin, Male, Metabolic Networks and Pathways, Mice, Osmolar Concentration, Quantitative Trait Loci
Abstract

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

DOI10.1038/ng.2385
Alternate JournalNat. Genet.
PubMed ID22885924