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

dc.contributor.authorYaghootkar, Hanieh
dc.contributor.authorLotta, Luca
dc.contributor.authorTyrrell, Jessica
dc.contributor.authorSmit, Roelof AJ
dc.contributor.authorJones, Sam E
dc.contributor.authorDonnelly, Louise
dc.contributor.authorBeaumont, Robin
dc.contributor.authorCampbell, Archie
dc.contributor.authorTuke, Marcus A
dc.contributor.authorHayward, Caroline
dc.contributor.authorRuth, Katherine S
dc.contributor.authorPadmanabhan, Sandosh
dc.contributor.authorJukema, J Wouter
dc.contributor.authorPalmer, Colin C
dc.contributor.authorHattersley, Andrew
dc.contributor.authorFreathy, Rachel M
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorWareham, Nicholas
dc.contributor.authorWood, Andrew R
dc.contributor.authorMurray, Anna
dc.contributor.authorWeedon, Michael N
dc.contributor.authorSattar, Naveed
dc.contributor.authorPearson, Ewan
dc.contributor.authorScott, Robert
dc.contributor.authorFrayling, Timothy M
dc.contributor.otherBiology
dc.contributor.otherSustainable Energy, Air & Water Technology (DuEL)
dc.date.accessioned2019-04-26T08:57:11Z
dc.date.available2019-04-26T08:57:11Z
dc.date.issued26/04/16
dc.descriptionRecent genetic studies have identified some alleles 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, 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.urihttps://demo7.dspace.org/handle/10673/457
dc.languageen
dc.publisherAmerican Diabetes Association
dc.titleGenetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension and heart disease.
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