Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. / Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC); Lagou, Vasiliki; Krus, Ulrika; Groop, Leif; Tuomi, Tiinamaija; Lyssenko, Valeriya; Prokopenko, Inga.

In: Nature Communications, Vol. 12, No. 1, 24, 2021.

Research output: Contribution to journalArticle

Harvard

Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), Lagou, V, Krus, U, Groop, L, Tuomi, T, Lyssenko, V & Prokopenko, I 2021, 'Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability', Nature Communications, vol. 12, no. 1, 24. https://doi.org/10.1038/s41467-020-19366-9

APA

Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), Lagou, V., Krus, U., Groop, L., Tuomi, T., Lyssenko, V., & Prokopenko, I. (2021). Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. Nature Communications, 12(1), [24]. https://doi.org/10.1038/s41467-020-19366-9

CBE

Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), Lagou V, Krus U, Groop L, Tuomi T, Lyssenko V, Prokopenko I. 2021. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. Nature Communications. 12(1):Article 24. https://doi.org/10.1038/s41467-020-19366-9

MLA

Vancouver

Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), Lagou V, Krus U, Groop L, Tuomi T, Lyssenko V et al. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. Nature Communications. 2021;12(1). 24. https://doi.org/10.1038/s41467-020-19366-9

Author

Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) ; Lagou, Vasiliki ; Krus, Ulrika ; Groop, Leif ; Tuomi, Tiinamaija ; Lyssenko, Valeriya ; Prokopenko, Inga. / Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability. In: Nature Communications. 2021 ; Vol. 12, No. 1.

RIS

TY - JOUR

T1 - Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

AU - Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)

AU - Lagou, Vasiliki

AU - Krus, Ulrika

AU - Groop, Leif

AU - Tuomi, Tiinamaija

AU - Lyssenko, Valeriya

AU - Prokopenko, Inga

PY - 2021

Y1 - 2021

N2 - Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes. © 2021, The Author(s).

AB - Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes. © 2021, The Author(s).

U2 - 10.1038/s41467-020-19366-9

DO - 10.1038/s41467-020-19366-9

M3 - Article

C2 - 33402679

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 24

ER -