Abstract:
:Genome-wide association studies have identified common variants that only partially explain the genetic risk for type 2 diabetes (T2D). Using genome-wide association data from 1,376 French individuals, we identified 16,360 SNPs nominally associated with T2D and studied these SNPs in an independent sample of 4,977 French individuals. We then selected the 28 best hits for replication in 7,698 Danish subjects and identified 4 SNPs showing strong association with T2D, one of which (rs2943641, P = 9.3 x 10(-12), OR = 1.19) was located adjacent to the insulin receptor substrate 1 gene (IRS1). Unlike previously reported T2D risk loci, which predominantly associate with impaired beta cell function, the C allele of rs2943641 was associated with insulin resistance and hyperinsulinemia in 14,358 French, Danish and Finnish participants from population-based cohorts; this allele was also associated with reduced basal levels of IRS1 protein and decreased insulin induction of IRS1-associated phosphatidylinositol-3-OH kinase activity in human skeletal muscle biopsies.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Rung J,Cauchi S,Albrechtsen A,Shen L,Rocheleau G,Cavalcanti-Proença C,Bacot F,Balkau B,Belisle A,Borch-Johnsen K,Charpentier G,Dina C,Durand E,Elliott P,Hadjadj S,Järvelin MR,Laitinen J,Lauritzen T,Marre M,Mazur A,doi
10.1038/ng.443subject
Has Abstractpub_date
2009-10-01 00:00:00pages
1110-5issue
10eissn
1061-4036issn
1546-1718pii
ng.443journal_volume
41pub_type
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