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

Mansour Aly, Dina LU ; Dwivedi, Om Prakash ; Prasad, Rashmi B LU ; Käräjämäki, Annemari ; Hjort, Rebecka ; Thangam, Manonanthini LU ; Åkerlund, Mikael LU ; Mahajan, Anubha ; Udler, Miriam S and Florez, Jose C , et al. (2021) In Nature Genetics 53. p.1534-1542
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... (More)

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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type
Contribution to journal
publication status
published
subject
keywords
ANDIS, diabetes
in
Nature Genetics
volume
53
pages
1534 - 1542
publisher
Nature Publishing Group
external identifiers
  • scopus:85121947847
  • pmid:34737425
ISSN
1546-1718
DOI
10.1038/s41588-021-00948-2
language
English
LU publication?
yes
additional info
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
id
6ed784f1-24f1-4a0d-9b59-ba9be7d1a5e1
date added to LUP
2021-11-08 11:01:07
date last changed
2024-06-24 13:34:17
@article{6ed784f1-24f1-4a0d-9b59-ba9be7d1a5e1,
  abstract     = {{<p>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.</p>}},
  author       = {{Mansour Aly, Dina and Dwivedi, Om Prakash and Prasad, Rashmi B and Käräjämäki, Annemari and Hjort, Rebecka and Thangam, Manonanthini and Åkerlund, Mikael and Mahajan, Anubha and Udler, Miriam S and Florez, Jose C and McCarthy, Mark I and Brosnan, Julia and Melander, Olle and Carlsson, Sofia and Hansson, Ola and Tuomi, Tiinamaija and Groop, Leif and Ahlqvist, Emma}},
  issn         = {{1546-1718}},
  keywords     = {{ANDIS; diabetes}},
  language     = {{eng}},
  pages        = {{1534--1542}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes}},
  url          = {{http://dx.doi.org/10.1038/s41588-021-00948-2}},
  doi          = {{10.1038/s41588-021-00948-2}},
  volume       = {{53}},
  year         = {{2021}},
}