| Literature DB >> 28783164 |
Erna V Ivarsdottir1,2, Valgerdur Steinthorsdottir1, Maryam S Daneshpour3, Gudmar Thorleifsson1, Patrick Sulem1, Hilma Holm1, Snaevar Sigurdsson1, Astradur B Hreidarsson4, Gunnar Sigurdsson4, Ragnar Bjarnason5,6, Arni V Thorsson5, Rafn Benediktsson4,6, Gudmundur Eyjolfsson7, Olof Sigurdardottir8, Isleifur Olafsson9, Sirous Zeinali10, Fereidoun Azizi11, Unnur Thorsteinsdottir1,6, Daniel F Gudbjartsson1,2, Kari Stefansson1,6.
Abstract
Sequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.7% per allele, P = 4.2 × 10-10), whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance (7.5% per allele, P = 4.9 × 10-11 and 7.3% per allele, P = 7.5 × 10-18, respectively). Variants that increase mean and between-subject variance in fasting glucose levels tend to increase T2D risk, whereas those that increase the mean but reduce variance do not (r2 = 0.61). The variants that increase between-subject variance increase fasting glucose heritability estimates. Intuitively, our results show that increasing the mean and variance of glucose levels is more likely to cause pathologically high glucose levels than increase in the mean offset by a decrease in variance.Entities:
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Year: 2017 PMID： 28783164 DOI： 10.1038/ng.3928
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330