Genetics of Type 2 Diabetes

Endocrine Development
Alena Stančáková, Markku Laakso

Abstract

Genetic and environmental factors as well as their interactions contribute to the pathogenesis of type 2 diabetes. Linkage analysis, candidate gene approaches, genome-wide association studies, and sequencing have been used in the identification of common, low-frequency and rare variants for type 2 diabetes. Genome-wide association studies have identified >80 common variants for type 2 diabetes, with small effect sizes (risk of type 2 diabetes increased by 5-40%). Almost all of these variants regulate insulin secretion, and only a few regulate insulin sensitivity. Common variants capture only ∼10% of the heritability of type 2 diabetes. Low-frequency and rare variants with large effects have also been identified, but their contribution to 'missing heritability' at the population level is limited. Gene-environment and gene-gene interactions and epigenetics are likely to contribute to the missing heritability of type 2 diabetes. Epigenetic factors (DNA methylations and histone modifications) are especially important because they might mediate the effects of environmental exposures on the risk of type 2 diabetes. Although understanding of the genetics of type 2 diabetes has exhibited great progress in the past few years, a substant...Continue Reading

Citations

Apr 12, 2017·Expert Opinion on Therapeutic Targets·Francesca FioryFrancesco Beguinot
Jun 3, 2017·International Journal of Molecular Sciences·Ángeles OrtegaBernat Soria
Dec 17, 2017·Journal of Inherited Metabolic Disease·Juergen Grulich-Henn, Daniela Klose
Jun 14, 2017·BioMed Research International·Eiralí Guadalupe García-ChapaJuan Pablo Meza-Espinoza
Jun 19, 2020·Journal of Diabetes and Metabolic Disorders·Taraneh ErfaniMandana Hasanzad
Sep 22, 2017·Diabetes Care·Bernard ZinmanEle Ferrannini
Jan 2, 2019·BioMed Research International·Yijun WangChun Wang
Dec 12, 2019·Frontiers in Endocrinology·Saras SaraswathiKhalid Hussain
Mar 13, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Paola MirraFrancesco Beguinot
Apr 17, 2020·Molecular Metabolism·Dassine BerdousBernard Thorens
Mar 24, 2021·Journal of Medical Genetics·Haipeng PangZhiguang Zhou
Jul 31, 2021·Molecular Biology Reports·Lucie DlouhaJaroslav A Hubacek

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