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Using genetic variants to assess the relationship between circulating lipids and type 2 diabetes.

Fall, Tove LU ; Xie, Weijia; Poon, Wenny LU ; Yaghootkar, Hanieh; Mägi, Reedik; Knowles, Joshua W; Lyssenko, Valeriya LU ; Weedon, Michael; Frayling, Timothy M and Ingelsson, Erik (2015) In Diabetes 64(7). p.2676-2684
Abstract
The effects of dyslipidemia on the risk of type 2 diabetes (T2D) and related traits are not clear. We used regression models and 140 lipid-associated genetic variants to estimate associations between circulating HDL-cholesterol, LDL-cholesterol and triglycerides, and T2D and related traits. Each genetic test was corrected for effects of variants on the other two lipid types and surrogates of adiposity. We used the largest datasets available - 34,840 T2D cases and 114,981 controls from the DIAGRAM consortium and up to 133,010 non-diabetic individuals for insulin secretion and sensitivity, from the MAGIC and GENESIS studies.Eight out of 21 associations between groups of variants and diabetes traits were significant at the nominal level,... (More)
The effects of dyslipidemia on the risk of type 2 diabetes (T2D) and related traits are not clear. We used regression models and 140 lipid-associated genetic variants to estimate associations between circulating HDL-cholesterol, LDL-cholesterol and triglycerides, and T2D and related traits. Each genetic test was corrected for effects of variants on the other two lipid types and surrogates of adiposity. We used the largest datasets available - 34,840 T2D cases and 114,981 controls from the DIAGRAM consortium and up to 133,010 non-diabetic individuals for insulin secretion and sensitivity, from the MAGIC and GENESIS studies.Eight out of 21 associations between groups of variants and diabetes traits were significant at the nominal level, including those between genetically determined lower HDL-C (β=-0.12, P=0.03) and T2D, and genetically determined lower LDL-C (β =-0.21, P=5x10(-6)) and T2D. While some of these may represent causal associations, we discuss why caution must be used when using Mendelian randomization in the context of circulating lipid levels and diabetes traits. In conclusion, we found evidence of links between genetic variants associated with lipids and T2D, but deepened knowledge of the underlying genetic mechanisms of specific lipid variants is needed before drawing definite conclusions about causality using Mendelian randomization methodology. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
64
issue
7
pages
2676 - 2684
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:25948681
  • wos:000356934000049
  • scopus:84946509188
ISSN
1939-327X
DOI
10.2337/db14-1710
language
English
LU publication?
yes
id
1df6c8ea-edd5-428a-9057-709ee846dbf3 (old id 5456752)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25948681?dopt=Abstract
date added to LUP
2015-06-04 14:33:14
date last changed
2017-10-22 03:04:17
@article{1df6c8ea-edd5-428a-9057-709ee846dbf3,
  abstract     = {The effects of dyslipidemia on the risk of type 2 diabetes (T2D) and related traits are not clear. We used regression models and 140 lipid-associated genetic variants to estimate associations between circulating HDL-cholesterol, LDL-cholesterol and triglycerides, and T2D and related traits. Each genetic test was corrected for effects of variants on the other two lipid types and surrogates of adiposity. We used the largest datasets available - 34,840 T2D cases and 114,981 controls from the DIAGRAM consortium and up to 133,010 non-diabetic individuals for insulin secretion and sensitivity, from the MAGIC and GENESIS studies.Eight out of 21 associations between groups of variants and diabetes traits were significant at the nominal level, including those between genetically determined lower HDL-C (β=-0.12, P=0.03) and T2D, and genetically determined lower LDL-C (β =-0.21, P=5x10(-6)) and T2D. While some of these may represent causal associations, we discuss why caution must be used when using Mendelian randomization in the context of circulating lipid levels and diabetes traits. In conclusion, we found evidence of links between genetic variants associated with lipids and T2D, but deepened knowledge of the underlying genetic mechanisms of specific lipid variants is needed before drawing definite conclusions about causality using Mendelian randomization methodology.},
  author       = {Fall, Tove and Xie, Weijia and Poon, Wenny and Yaghootkar, Hanieh and Mägi, Reedik and Knowles, Joshua W and Lyssenko, Valeriya and Weedon, Michael and Frayling, Timothy M and Ingelsson, Erik},
  issn         = {1939-327X},
  language     = {eng},
  number       = {7},
  pages        = {2676--2684},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Using genetic variants to assess the relationship between circulating lipids and type 2 diabetes.},
  url          = {http://dx.doi.org/10.2337/db14-1710},
  volume       = {64},
  year         = {2015},
}