Effect of sequence variants on variance in glucose levels predicts type 2 diabetes risk and accounts for heritability View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-09

AUTHORS

Erna V Ivarsdottir, Valgerdur Steinthorsdottir, Maryam S Daneshpour, Gudmar Thorleifsson, Patrick Sulem, Hilma Holm, Snaevar Sigurdsson, Astradur B Hreidarsson, Gunnar Sigurdsson, Ragnar Bjarnason, Arni V Thorsson, Rafn Benediktsson, Gudmundur Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Sirous Zeinali, Fereidoun Azizi, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Kari Stefansson

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. More... »

PAGES

1398-1402

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3928

    DOI

    http://dx.doi.org/10.1038/ng.3928

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1091083453

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28783164


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