Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

By Benjamin F. Voight, L. Scott, V. Steinthorsdottir, Andrew P. Morris, C. Dina, R. Welch, Eleftheria Zeggini, C. Huth, Yurii S. Aulchenko, G. Thorleifsson and 148 more. Nature Genetics, 2010

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By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 × 10−8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/09e6d84f8173c13a96820c4d08e418c73b85be1f

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Citations in the corpus

Pathogenesis of Type 2 Diabetes Mellitus (2015, neutral): “A great number of studies have suggested that genetic variants in or near KCNJ11, TCF7L2, WFS1, HNF1B, IGF2BP2, CDKN2ACDKN2B, CDKAL1, SLC30A8, HHEX/IDE, KCNQ1, THADA, TSPAN8/ LGR5, DC123/CAMK1D, JAZF1, MTNR1B, DGKB/TMEM195, GCK, PROX1, ADCY5, SRR, CENTD2, ST6GAL1, HNF4A, KCNK16, FITM2-R3HDML-HNF4A, ”
Beta Cell Dysfunction and Insulin Resistance (2013, background): “…architecture of quantitative indices of beta cell function and of insulin resistance differ markedly: given the same individuals, sample sizes, and biochemical measurements, more signals were described for beta cell function compared to insulin resistance (Dupuis et al., 2010; Voight et al., 2010).”
Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus (2016, background): “Furthermore, one locus near dual specificity phosphatase 9 on the X chromosome is directly associated with higher T2DM risk (192).”
Genetics of type 2 diabetes. (2011, neutral): “In June 2010 the DIAGRAM consortium was complemented with additional GWAS cohorts from deCODE genetics, the Diabetes Gene Discovery group, the KORA group, the Rotterdam study, and EUROSPAN to form DIAGRAM plus, with a higher effective sample size (n 22 044) (41).”
The genetic architecture of type 2 diabetes (2016, neutral): “We then assigned names to the resulting state definitions: (1) H3K4me3, H3K27ac (active promoter); (2) H3K4me3, H3K27ac, H3K4me1 (active enhancer 1); (3) H3K27ac, H3K4me1 (active enhancer 2); (4) H3K4me1 (weak enhancer); (5) H3K27me3, H3K4me3, H3K4me1 (poised promoter); (6) H3K27me3 (repressed); (7)”
Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians (2011, background): “Although the function of ZFAND3 has not been fully elucidated, it is noteworthy that a member of the same gene family, ZFAND6 , is present along with FAH at a previously detected T2D locu”
Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention (2014, neutral): “8×10-13 [26]”
Systems genetics approaches to understand complex traits (2013, background): “…syndrome traits Variants that are located near the maternally expressed imprinted Krüppel-like factor 14 gene ( KLF14 ) have been associated with type 2 diabetes (T2D) 120 and with high-density lipoprotein (HDL) cholesterol levels 121 in genome-wide association studies (GWASs) (see the figure).”