| Literature DB >> 34737425 |
Dina Mansour Aly1, Om Prakash Dwivedi2, Rashmi B Prasad1, Annemari Käräjämäki3,4, Rebecka Hjort5, Manonanthini Thangam1, Mikael Åkerlund1, Anubha Mahajan6,7, Miriam S Udler8,9,10, Jose C Florez8,9,10, Mark I McCarthy11,12,13,7, Julia Brosnan14, Olle Melander1, Sofia Carlsson5, Ola Hansson1,2, Tiinamaija Tuomi1,2,15,16, Leif Groop1,2, Emma Ahlqvist17.
Abstract
Type 2 diabetes has been reproducibly clustered into five subtypes with different disease progression and risk of complications; however, etiological differences are unknown. We used genome-wide association and genetic risk score (GRS) analysis to compare the underlying genetic drivers. Individuals from the Swedish ANDIS (All New Diabetics In Scania) study were compared to individuals without diabetes; the Finnish DIREVA (Diabetes register in Vasa) and Botnia studies were used for replication. We show that subtypes differ with regard to family history of diabetes and association with GRS for diabetes-related traits. The severe insulin-resistant subtype was uniquely associated with GRS for fasting insulin but not with variants in the TCF7L2 locus or GRS reflecting insulin secretion. Further, an SNP (rs10824307) near LRMDA was uniquely associated with mild obesity-related diabetes. Therefore, we conclude that the subtypes have partially distinct genetic backgrounds indicating etiological differences.Entities:
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Year: 2021 PMID： 34737425 DOI： 10.1038/s41588-021-00948-2
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330