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. 2021 Nov;53(11):1534-1542.
doi: 10.1038/s41588-021-00948-2. Epub 2021 Nov 4.

Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes

Dina Mansour Aly  1 , Om Prakash Dwivedi  2 , Rashmi B Prasad  1 , Annemari Käräjämäki  3   4 , Rebecka Hjort  5 , Manonanthini Thangam  1 , Mikael Åkerlund  1 , Anubha Mahajan  6   7 , Miriam S Udler  8   9   10 , Jose C Florez  8   9   10 , Mark I McCarthy  11   12   13   7 ; Regeneron Genetics Center; Julia Brosnan  14 , Olle Melander  1 , Sofia Carlsson  5 , Ola Hansson  1   2 , Tiinamaija Tuomi  1   2   15   16 , Leif Groop  1   2 , Emma Ahlqvist  17
Collaborators, Affiliations

Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes

Dina Mansour Aly et al. Nat Genet. 2021 Nov.

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.

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References

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