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PLoS One. 2018 Feb 14;13(2):e0192696. doi: 10.1371/journal.pone.0192696. eCollection 2018.

Identifying genetic risk loci for diabetic complications and showing evidence for heterogeneity of type 1 diabetes based on complications risk.

Author information

1
Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
2
Children's Hospital Oakland Research Institute, Oakland, California, United States of America.
3
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
4
Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
5
Battelle Center for Mathematical Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States of America.
6
Department of Pediatrics, Wexner Medical Center, Ohio State University, Columbus, Ohio, United States of America.

Abstract

There is a growing body of evidence suggesting that type 1 diabetes (T1D) is a genetically heterogeneous disease. However, the extent of this heterogeneity, and what observations may distinguish different forms, is unclear. One indicator may be T1D-related microvascular complications (MVCs), which are familial, but occur in some families, and not others. We tested the hypothesis that T1D plus MVC is genetically distinct from T1D without MCV. We studied 415 families (2,462 individuals, 896 with T1D) using genome-wide linkage analysis, comparing families with and without MVC. We also tested for interaction between identified loci and alleles at the HLA-DRB1 locus. We found significant linkage scores at 1p36.12, 1q32.1, 8q21.3, 12p11.21 and 22q11.21. In all regions except 1p36.12, linkage scores differed between MVC-based phenotype groups, suggesting that families with MVCs express different genetic influences than those without. Our linkage results also suggested gene-gene interaction between the above putative loci and the HLA region; HLA-based strata produced significantly increased linkage scores in some strata, but not others within a phenotype group. We conclude that families with type 1 diabetes plus MVCs are genetically different from those with diabetes alone.

PMID:
29444168
PMCID:
PMC5812614
DOI:
10.1371/journal.pone.0192696
[Indexed for MEDLINE]
Free PMC Article

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