| Literature DB >> 24464100 |
Valgerdur Steinthorsdottir1, Gudmar Thorleifsson1, Patrick Sulem1, Hannes Helgason2, Niels Grarup3, Asgeir Sigurdsson1, Hafdis T Helgadottir1, Hrefna Johannsdottir1, Olafur T Magnusson1, Sigurjon A Gudjonsson1, Johanne M Justesen3, Marie N Harder3, Marit E Jørgensen4, Cramer Christensen5, Ivan Brandslund6, Annelli Sandbæk7, Torsten Lauritzen7, Henrik Vestergaard3, Allan Linneberg8, Torben Jørgensen9, Torben Hansen3, Maryam S Daneshpour10, Mohammad-Sadegh Fallah10, Astradur B Hreidarsson11, Gunnar Sigurdsson11, Fereidoun Azizi12, Rafn Benediktsson11, Gisli Masson1, Agnar Helgason13, Augustine Kong2, Daniel F Gudbjartsson2, Oluf Pedersen3, Unnur Thorsteinsdottir14, Kari Stefansson14.
Abstract
Through whole-genome sequencing of 2,630 Icelanders and imputation into 11,114 Icelandic cases and 267,140 controls followed by testing in Danish and Iranian samples, we discovered 4 previously unreported variants affecting risk of type 2 diabetes (T2D). A low-frequency (1.47%) variant in intron 1 of CCND2, rs76895963[G], reduces risk of T2D by half (odds ratio (OR) = 0.53, P = 5.0 × 10(-21)) and is correlated with increased CCND2 expression. Notably, this variant is also associated with both greater height and higher body mass index (1.17 cm per allele, P = 5.5 × 10(-12) and 0.56 kg/m(2) per allele, P = 6.5 × 10(-7), respectively). In addition, two missense variants in PAM, encoding p.Asp563Gly (frequency of 4.98%) and p.Ser539Trp (frequency of 0.65%), confer moderately higher risk of T2D (OR = 1.23, P = 3.9 × 10(-10) and OR = 1.47, P = 1.7 × 10(-5), respectively), and a rare (0.20%) frameshift variant in PDX1, encoding p.Gly218Alafs*12, associates with high risk of T2D (OR = 2.27, P = 7.3 × 10(-7)).Entities:
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Year: 2014 PMID： 24464100 DOI： 10.1038/ng.2882
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330