Using genetic variants to assess the relationship between circulating lipids and type 2 diabetes.
(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:
https://lup.lub.lu.se/record/5456752
- author
- 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
- organization
- publishing date
- 2015
- 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
- pmid:25948681
- 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
- 2016-04-01 09:59:03
- date last changed
- 2024-04-21 00:34:22
@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}}, doi = {{10.2337/db14-1710}}, volume = {{64}}, year = {{2015}}, }