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The Influence of Rare Genetic Variation in SLC30A8 on Diabetes Incidence and beta-Cell Function

Billings, Liana K.; Jablonski, Kathleen A.; Ackerman, Rachel J.; Taylor, Andrew; Fanelli, Rebecca R.; McAteer, Jarred B.; Guiducci, Candace; Delahanty, Linda M.; Dabelea, Dana and Kahn, Steven E., et al. (2014) In Journal of Clinical Endocrinology and Metabolism 99(5). p.926-930
Abstract
Context/Objective: The variant rs13266634 in SLC30A8, encoding a beta-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair beta-cell function, and test whether zinc intake modifies this risk. Design/Outcome: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and identified 44 novel variants, which were genotyped in 3445 DPP participants and tested for association with diabetes incidence and measures of insulin secretion and processing. We examined individual common variants and used gene burden tests to test 39 rare variants in aggregate. Results: We detected a near-nominal association between a rare-variant... (More)
Context/Objective: The variant rs13266634 in SLC30A8, encoding a beta-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair beta-cell function, and test whether zinc intake modifies this risk. Design/Outcome: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and identified 44 novel variants, which were genotyped in 3445 DPP participants and tested for association with diabetes incidence and measures of insulin secretion and processing. We examined individual common variants and used gene burden tests to test 39 rare variants in aggregate. Results: We detected a near-nominal association between a rare-variant genotype risk score and diabetes risk. Five common variants were associated with the oral disposition index. Various methods aggregating rare variants demonstrated associations with changes in oral disposition index and insulinogenic index during year 1 of follow-up. We did not find a clear interaction of zinc intake with genotype on diabetes incidence. Conclusions: Individual common and an aggregate of rare genetic variation in SLC30A8 are associated with measures of beta-cell function in the DPP. Exploring rare variation may complement ongoing efforts to uncover the genetic influences that underlie complex diseases. (Less)
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publication status
published
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Journal of Clinical Endocrinology and Metabolism
volume
99
issue
5
pages
926 - 930
publisher
The Endocrine Society
external identifiers
  • wos:000342339800025
  • scopus:84899963164
ISSN
1945-7197
DOI
10.1210/jc.2013-2378
language
English
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yes
id
095ad728-90f6-446b-922a-aa7289785055 (old id 4803670)
date added to LUP
2014-12-01 07:38:04
date last changed
2017-04-09 03:50:28
@article{095ad728-90f6-446b-922a-aa7289785055,
  abstract     = {Context/Objective: The variant rs13266634 in SLC30A8, encoding a beta-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair beta-cell function, and test whether zinc intake modifies this risk. Design/Outcome: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and identified 44 novel variants, which were genotyped in 3445 DPP participants and tested for association with diabetes incidence and measures of insulin secretion and processing. We examined individual common variants and used gene burden tests to test 39 rare variants in aggregate. Results: We detected a near-nominal association between a rare-variant genotype risk score and diabetes risk. Five common variants were associated with the oral disposition index. Various methods aggregating rare variants demonstrated associations with changes in oral disposition index and insulinogenic index during year 1 of follow-up. We did not find a clear interaction of zinc intake with genotype on diabetes incidence. Conclusions: Individual common and an aggregate of rare genetic variation in SLC30A8 are associated with measures of beta-cell function in the DPP. Exploring rare variation may complement ongoing efforts to uncover the genetic influences that underlie complex diseases.},
  author       = {Billings, Liana K. and Jablonski, Kathleen A. and Ackerman, Rachel J. and Taylor, Andrew and Fanelli, Rebecca R. and McAteer, Jarred B. and Guiducci, Candace and Delahanty, Linda M. and Dabelea, Dana and Kahn, Steven E. and Franks, Paul and Hanson, Robert L. and Maruthur, Nisa M. and Shuldiner, Alan R. and Mayer-Davis, Elizabeth J. and Knowler, William C. and Florez, Jose C.},
  issn         = {1945-7197},
  language     = {eng},
  number       = {5},
  pages        = {926--930},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {The Influence of Rare Genetic Variation in SLC30A8 on Diabetes Incidence and beta-Cell Function},
  url          = {http://dx.doi.org/10.1210/jc.2013-2378},
  volume       = {99},
  year         = {2014},
}