@article{Nelson2017,
title = {Association analyses based on false discovery rate implicate 243 susceptibility loci for coronary artery disease},
author = {CP Nelson, A Goel, A Butterworth},
url = {http://eprints.whiterose.ac.uk/116865/},
year = {2017},
date = {2017-05-25},
abstract = {Genome-wide association studies (GWAS) in coronary artery disease (CAD) have identified 66 loci at ‘genome-wide significance’ (p < 5 × 10-8) but a much larger number of putative loci at a false discovery rate (FDR) of 5%1-4. Here, we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; Ncases=10,801) as well as a stricter definition without it (HARD; Ncases=6,482) and selected the former for conducting a meta-analysis with the two most recent CAD GWASs2-3. This approach identified 13 new loci at genome-wide significance, 12 of which were in our previous 5% FDR list2, and provided strong support that the remaining FDR loci represent genuine signals. The set of 304 independent variants at 5% FDR in this study explain 21.2% of CAD heritability and identified 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.},
keywords = {11223, coronary artery disease},
pubstate = {published},
tppubtype = {article}
}

@article{LyallDM2016b,
title = {Associations between single and multiple cardiometabolic diseases and cognitive abilities in 474 129 UK Biobank participants},
author = {Lyall, D.
Celis, C.
Anderson, J.
Gill, J. M.
Mackay, D.
McIntosh, A.
Smith, D. J.
Deary, I.
Sattar, N.
Pell, J.},
url = {http://eurheartj.oxfordjournals.org/content/early/2016/11/13/eurheartj.ehw528},
year = {2016},
date = {2016-11-16},
journal = {European Heart Journal},
abstract = {Aims Cardiometabolic diseases (hypertension, coronary artery disease [CAD] and diabetes are known to associate with poorer cognitive ability but there are limited data on whether having more than one of these conditions is associated with additive effects. We aimed to quantify the magnitude of their associations with non-demented cognitive abilities and determine the extent to which these associations were additive.
Methods and results We examined cognitive test scores in domains of reasoning, information processing speed and memory, included as part of the baseline UK Biobank cohort assessment (N = 474 129 with relevant data), adjusting for a range of potentially confounding variables. The presence of hypertension, CAD and diabetes generally associated with poorer cognitive scores on all tests, compared with a control group that reported none of these diseases. There was evidence of an additive deleterious dose effect of an increasing number of cardiometabolic diseases, for reasoning scores (unstandardized additive dose beta per disease = −0.052 score points out of 13, 95% CI [confidence intervals] −0.063 to − 0.041, P < 0.001), log reaction time scores (exponentiated beta = 1.005, i.e. 0.5% slower, 95% CI 1.004–1.005, P < 0.001) and log memory errors (exponentiated beta = 1.005 i.e. 0.5% more errors; 95% CI 1.003–1.008).
Conclusion Cardiometabolic diseases are associated with worse cognitive abilities, and the potential effect of an increasing number of cardiometabolic conditions appears additive. These results reinforce the notion that preventing or delaying cardiovascular disease or diabetes may delay cognitive decline and possible dementia.},
keywords = {cognitive ability, coronary artery disease, diabetes, hypertension},
pubstate = {published},
tppubtype = {article}
}

@article{Hagenaars2016b,
title = {Polygenic risk for coronary artery disease is associated with cognitive ability in older adults},
author = {Saskia P. Hagenaars, Sarah E. Harris, Toni-Kim Clarke, Lynsey Hall, Michelle Luciano, Ana Maria Fernandez-Pujals, Gail Davies, Caroline Hayward, Generation Scotland, John M. Starr, David J. Porteous, Andrew M. McIntosh, Ian J. Deary },
url = {http://ije.oxfordjournals.org/content/early/2016/01/28/ije.dyv354.abstract},
year = {2016},
date = {2016-01-28},
journal = {International Journal of Epidemiology},
abstract = {Background: Coronary artery disease (CAD) is associated with cognitive decrements and risk of later dementia, but it is not known if shared genetic factors underlie this association. We tested whether polygenic risk for CAD was associated with cognitive ability in community-dwelling cohorts of middle-aged and older adults.

Methods: Individuals from Generation Scotland: Scottish Family Health Study (GS:SFHS, N = 9865) and from the Lothian Birth Cohorts of 1921 (LBC1921, N = 517) and 1936 (LBC1936, N = 1005) provided cognitive data and genome-wide genotype data. Polygenic risk profile scores for CAD were calculated for all of the cohorts using the largest available genome-wide association studies (GWAS) data set, the CARDIoGRAM consortium (22 233 cases and 64 762 controls). Polygenic risk profile scores for CAD were then tested for their association with cognitive abilities in the presence and absence of manifest cardiovascular disease.

Results: A meta-analysis of all three cohorts showed a negative association between CAD polygenic risk and fluid cognitive ability (β = −0.022, P = 0.016), verbal intelligence (β = −0.024, P = 0.011) and memory (β = −0.021, P = 0.028).

Conclusions: Increased polygenic risk for CAD is associated with lower cognitive ability in older adults. Common genetic variants may underlie some of the association between age-related cognitive decrements and the risk for CAD. },
keywords = {7898, coronary artery disease},
pubstate = {published},
tppubtype = {article}
}

@misc{Yaghootkar2015,
title = {GENETIC VARIANTS ASSOCIATED WITH LOWER BMI AND LOWER BODY FAT PERCENTAGE INCREASE THE RISK OF TYPE 2 DIABETES, HYPERTENSION AND CORONARY ARTERY DISEASE IN THE UK BIOBANK STUDY.},
author = {Hanieh Yaghootkar, Robin Beaumont, Jessica Tyrrell, Samuel Jones, Andrew Wood, Marcus Tuke, Katherine Ruth, Rachel Freathy, Anna Murray, Michael Weedon, Timothy Frayling},
year = {2015},
date = {2015-09-04},
abstract = {The UK Biobank study was designed to understand the role of genes, environment and their interaction in disease. Previous smaller studies have shown that many obese individuals are metabolically healthy whilst many normal weight individuals can have an elevated risk of metabolic diseases such as type 2 diabetes, coronary artery disease and hypertension. Further studies are needed to investigate the potential role of a shared genetic etiology between these diseases that is independent from obesity. We aimed to use the initial release of genetic data from 120,000 ancestrally British UK Biobank individuals to test the hypothesis that some individuals are genetically predisposed to metabolic disease independently of higher BMI.

We selected 11 common genetic variants previously associated with insulin resistance and metabolic diseases from previously published GWAS data. We tested these variants individually and as a genetic risk score in the 120,000 UK Biobank individuals.

Alleles in or near the LYPLAL1, GRB14, IRS1, PPARG, FAM13A, PDGFC, PEPD and ANKRD55 genes, previously associated with higher insulin resistance, were associated with reduced body fat percentage in UK Biobank (N=118,012, p-values ranging from 0.05 to 9E-11). An insulin resistance genetic risk score consisting of all 11 variants was associated with lower BMI (-0.05kg/m2 per weighted allele [-0.06,-0.03], p=2E-7), lower body fat percentage (-0.13% [-0.15,-0.1], p=2E-27) but only nominally with fat free mass (0.03Kg [0.01,0.05], p=0.01).

Despite this association with lower adiposity the insulin resistance genetic risk score was associated with higher systolic (0.26mmHg [0.18,0.33], p=2E-10) and diastolic blood pressure(0.10 mmHg [0.05,0.14], p=6E-5), and greater risk of hypertension(OR 1.02 [1.01,1.03], p=3E-6, 65,976 cases), type 2 diabetes (OR 1.06 [1.04,1.08], p=2E-8, 4,040 cases) and coronary artery disease(OR 1.03 [1.02,1.05], p=1E-4, 5,807 cases).

The UK Biobank data provide evidence for shared genetic factors that predispose to type 2 diabetes, hypertension and coronary artery disease independently of obesity and suggest that reduced adipose tissue capacity is a likely contributory mechanism.},
keywords = {9055, 9072, coronary artery disease, diabetes, hypertension},
pubstate = {published},
tppubtype = {presentation}
}