Publication:
Genetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension and heart disease.

dc.contributor.author Yaghootkar, Hanieh
dc.contributor.author Lotta, Luca
dc.contributor.author Tyrrell, Jessica
dc.contributor.author Smit, Roelof AJ
dc.contributor.author Jones, Sam E
dc.contributor.author Donnelly, Louise
dc.contributor.author Beaumont, Robin
dc.contributor.author Campbell, Archie
dc.contributor.author Tuke, Marcus A
dc.contributor.author Hayward, Caroline
dc.contributor.author Ruth, Katherine S
dc.contributor.author Padmanabhan, Sandosh
dc.contributor.author Jukema, J Wouter
dc.contributor.author Palmer, Colin C
dc.contributor.author Hattersley, Andrew
dc.contributor.author Freathy, Rachel M
dc.contributor.author Langenberg, Claudia
dc.contributor.author Wareham, Nicholas
dc.contributor.author Wood, Andrew R
dc.contributor.author Murray, Anna
dc.contributor.author Weedon, Michael N
dc.contributor.author Sattar, Naveed
dc.contributor.author Pearson, Ewan
dc.contributor.author Scott, Robert
dc.contributor.author Frayling, Timothy M
dc.contributor.other Biology
dc.contributor.other Sustainable Energy, Air & Water Technology (DuEL)
dc.date.accessioned 2019-04-26T08:57:11Z
dc.date.available 2019-04-26T08:57:11Z
dc.date.issued 26/04/16
dc.description Recent genetic studies have identified some alleles associated with higher BMI but lower risk of type 2 diabetes, hypertension and heart disease. These ΓÇ£favorable adiposityΓÇ¥ 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, test for interactions between BMI and favorable adiposity genetics and 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/m2 [0.066,0.174]; p=1E-5) and higher body fat percentage (0.301 % [0.230,0.372]; p=1E-16) compared to the 50% of individuals carrying the fewest alleles. For a given BMI, the 50% of individuals carrying the most favourable adiposity alleles were at: 0.837 OR [0.784,0.894] lower risk of type 2 diabetes (p=1E-7), -0.859 mmHg [-1.099,-0.618] lower systolic (p=3E-12) and -0.394 mmHg [-0.534,-0.254] lower diastolic blood pressure (p=4E-8), 0.935 OR [0.911,0.958] lower risk of hypertension (p=1E-7) and 0.921 OR [0.872,0.973] lower risk of heart disease (p=3E-3). 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 favourable body fat distribution, with a lower waist-hip ratio (-0.004 [-0.005,-0.003] 50% vs 50%; p=3E-14) but in men, the favourable adiposity alleles were associated with higher waist circumference (0.454 cm [0.267,0.641] 50% vs 50%; p=2E-6) and higher waist-hip ratio (0.0013 [0.0003,0.0024] 50% vs 50%; p=0.01). Results were strengthened when meta-analysing with five additional studies. 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. While higher BMI is associated with higher risk of diseases, better fat storage capacity could reduce the risk.
dc.identifier.uri https://demo7.dspace.org/handle/10673/457
dc.language en
dc.publisher American Diabetes Association
dc.title Genetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension and heart disease.
dspace.entity.type Publication
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