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

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Authors
Ivarsdottir, Erna V
Steinthorsdottir, Valgerdur
Daneshpour, Maryam S
Thorleifsson, Gudmar
Sulem, Patrick
Holm, Hilma
Sigurdsson, Snaevar
Hreidarsson, Astradur B
Sigurdsson, Gunnar
Bjarnason, Ragnar
Thorsson, Arni V
Benediktsson, Rafn
Eyjolfsson, Gudmundur
Sigurdardottir, Olof
Olafsson, Isleifur
Zeinali, Sirous
Azizi, Fereidoun
Thorsteinsdottir, Unnur
Gudbjartsson, Daniel F
Stefansson, Kari
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Issue Date
2017-09

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Citation
Effect of sequence variants on variance in glucose levels predicts type 2 diabetes risk and accounts for heritability. 2017, 49 (9):1398-1402 Nat. Genet.
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 (r(2) = 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.
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https://www.nature.com/ng/journal/v49/n9/pdf/ng.3928.pdf
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Archived with thanks to Nature genetics
ae974a485f413a2113503eed53cd6c53
10.1038/ng.3928
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English Journal Articles (Peer Reviewed)

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