Genetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620284
Title:
Genetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease.
Authors:
Yaghootkar, H.; Lotta, L. A.; Tyrrell, J.; Smit, R. A. J.; Jones, S. E.; Donnelly, L.; Beaumont, R.; Campbell, A.; Tuke, M. A.; Hayward, C.; Ruth, K. S.; Padmanabhan, S.; Jukema, J. W.; Palmer, C. C.; Hattersley, Andrew T.; Freathy, R. M.; Langenberg, C.; Wareham, N. J.; Wood, A. R.; Murray, A.; Weedon, M. N.; Sattar, N.; Pearson, E.; Scott, R. A.; Frayling, T. M.
Abstract:
Recent genetic studies have identified some alleles that are associated with higher BMI but lower risk of type 2 diabetes, hypertension, and heart disease. These "favorable adiposity" alleles are collectively associated with lower insulin levels and higher subcutaneous-to-visceral adipose tissue ratio and may protect from disease through higher adipose storage capacity. We aimed to use data from 164,609 individuals from the UK Biobank and five other studies to replicate associations between a genetic score of 11 favorable adiposity variants and adiposity and risk of disease, to test for interactions between BMI and favorable adiposity genetics, and to test effects separately in men and women. In the UK Biobank, the 50% of individuals carrying the most favorable adiposity alleles had higher BMIs (0.120 kg/m(2) [95% CI 0.066, 0.174]; P = 1E-5) and higher body fat percentage (0.301% [0.230, 0.372]; P = 1E-16) compared with the 50% of individuals carrying the fewest alleles. For a given BMI, the 50% of individuals carrying the most favorable adiposity alleles were at lower risk of type 2 diabetes (odds ratio [OR] 0.837 [0.784, 0.894]; P = 1E-7), hypertension (OR 0.935 [0.911, 0.958]; P = 1E-7), and heart disease (OR 0.921 [0.872, 0.973]; P = 0.003) and had lower blood pressure (systolic -0.859 mmHg [-1.099, -0.618]; P = 3E-12 and diastolic -0.394 mmHg [-0.534, -0.254]; P = 4E-8). In women, these associations could be explained by the observation that the alleles associated with higher BMI but lower risk of disease were also associated with a favorable body fat distribution, with a lower waist-to-hip ratio (-0.004 cm [95% CI -0.005, -0.003] 50% vs. 50%; P = 3E-14), but in men, the favorable adiposity alleles were associated with higher waist circumference (0.454 cm [0.267, 0.641] 50% vs. 50%; P = 2E-6) and higher waist-to-hip ratio (0.0013 [0.0003, 0.0024] 50% vs. 50%; P = 0.01). Results were strengthened when a meta-analysis with five additional studies was conducted. There was no evidence of interaction between a genetic score consisting of known BMI variants and the favorable adiposity genetic score. In conclusion, different molecular mechanisms that lead to higher body fat percentage (with greater subcutaneous storage capacity) can have different impacts on cardiometabolic disease risk. Although higher BMI is associated with higher risk of diseases, better fat storage capacity could reduce the risk.
Citation:
Genetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease. 2016, 65 (8):2448-60 Diabetes
Publisher:
American Diabetes Association
Journal:
Diabetes
Issue Date:
Aug-2016
URI:
http://hdl.handle.net/11287/620284
DOI:
10.2337/db15-1671
PubMed ID:
27207519
Additional Links:
http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=27207519
Note:
This article is freely available. Click on the Additional Link above to access the full-text.
Type:
Journal Article
Language:
en
ISSN:
1939-327X
Appears in Collections:
Diabetes/Endocrine Services; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorYaghootkar, H.en
dc.contributor.authorLotta, L. A.en
dc.contributor.authorTyrrell, J.en
dc.contributor.authorSmit, R. A. J.en
dc.contributor.authorJones, S. E.en
dc.contributor.authorDonnelly, L.en
dc.contributor.authorBeaumont, R.en
dc.contributor.authorCampbell, A.en
dc.contributor.authorTuke, M. A.en
dc.contributor.authorHayward, C.en
dc.contributor.authorRuth, K. S.en
dc.contributor.authorPadmanabhan, S.en
dc.contributor.authorJukema, J. W.en
dc.contributor.authorPalmer, C. C.en
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorFreathy, R. M.en
dc.contributor.authorLangenberg, C.en
dc.contributor.authorWareham, N. J.en
dc.contributor.authorWood, A. R.en
dc.contributor.authorMurray, A.en
dc.contributor.authorWeedon, M. N.en
dc.contributor.authorSattar, N.en
dc.contributor.authorPearson, E.en
dc.contributor.authorScott, R. A.en
dc.contributor.authorFrayling, T. M.en
dc.date.accessioned2017-03-14T15:18:31Z-
dc.date.available2017-03-14T15:18:31Z-
dc.date.issued2016-08-
dc.identifier.citationGenetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease. 2016, 65 (8):2448-60 Diabetesen
dc.identifier.issn1939-327X-
dc.identifier.pmid27207519-
dc.identifier.doi10.2337/db15-1671-
dc.identifier.urihttp://hdl.handle.net/11287/620284-
dc.description.abstractRecent genetic studies have identified some alleles that are associated with higher BMI but lower risk of type 2 diabetes, hypertension, and heart disease. These "favorable adiposity" alleles are collectively associated with lower insulin levels and higher subcutaneous-to-visceral adipose tissue ratio and may protect from disease through higher adipose storage capacity. We aimed to use data from 164,609 individuals from the UK Biobank and five other studies to replicate associations between a genetic score of 11 favorable adiposity variants and adiposity and risk of disease, to test for interactions between BMI and favorable adiposity genetics, and to test effects separately in men and women. In the UK Biobank, the 50% of individuals carrying the most favorable adiposity alleles had higher BMIs (0.120 kg/m(2) [95% CI 0.066, 0.174]; P = 1E-5) and higher body fat percentage (0.301% [0.230, 0.372]; P = 1E-16) compared with the 50% of individuals carrying the fewest alleles. For a given BMI, the 50% of individuals carrying the most favorable adiposity alleles were at lower risk of type 2 diabetes (odds ratio [OR] 0.837 [0.784, 0.894]; P = 1E-7), hypertension (OR 0.935 [0.911, 0.958]; P = 1E-7), and heart disease (OR 0.921 [0.872, 0.973]; P = 0.003) and had lower blood pressure (systolic -0.859 mmHg [-1.099, -0.618]; P = 3E-12 and diastolic -0.394 mmHg [-0.534, -0.254]; P = 4E-8). In women, these associations could be explained by the observation that the alleles associated with higher BMI but lower risk of disease were also associated with a favorable body fat distribution, with a lower waist-to-hip ratio (-0.004 cm [95% CI -0.005, -0.003] 50% vs. 50%; P = 3E-14), but in men, the favorable adiposity alleles were associated with higher waist circumference (0.454 cm [0.267, 0.641] 50% vs. 50%; P = 2E-6) and higher waist-to-hip ratio (0.0013 [0.0003, 0.0024] 50% vs. 50%; P = 0.01). Results were strengthened when a meta-analysis with five additional studies was conducted. There was no evidence of interaction between a genetic score consisting of known BMI variants and the favorable adiposity genetic score. In conclusion, different molecular mechanisms that lead to higher body fat percentage (with greater subcutaneous storage capacity) can have different impacts on cardiometabolic disease risk. Although higher BMI is associated with higher risk of diseases, better fat storage capacity could reduce the risk.en
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.relation.urlhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=27207519en
dc.rightsArchived with thanks to Diabetesen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleGenetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease.en
dc.typeJournal Articleen
dc.identifier.journalDiabetesen
dc.description.noteThis article is freely available. Click on the Additional Link above to access the full-text.en
dc.type.versionPublisheden

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