OBJECTIVE: Circulating levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides are recognized risk factors for cardiovascular disease. We tested the hypothesis that the cumulative effects of common genetic variants for lipids are collectively associated with subclinical atherosclerosis and incident coronary heart disease. APPROACH AND RESULTS: Participants were drawn from the Erasmus Rucphen Family Study (n=2269) and the Rotterdam Study (n=8130). Linear regression and Cox proportional hazards models were applied to assess the influence of 4 risk scores derived from common genetic variants for lipids (total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglycerides) on carotid plaque, intima-media thickness, incident myocardial infarction, and coronary heart disease. Adjusted for age and sex, all 4 risk scores were associated with carotid plaque. This relationship was the strongest for the LDL-C score, which increased plaque score by 0.102 per SD increase in genetic risk score (P=3.2 × 10(-8)). The LDL-C score was also nominally associated with intima-media thickness, which increased 0.006 mm per SD increase in score (P=0.05). Both the total cholesterol and LDL-C scores were associated with incident myocardial infarction and coronary heart disease with hazard ratios between 1.10 and 1.13 per SD increase in score. Inclusion of additional risk factors as covariates minimally affected these results. CONCLUSIONS: Common genetic variants with small effects on lipid levels are, in combination, significantly associated with subclinical and clinical cardiovascular outcomes. As knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events.
OBJECTIVE: Circulating levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides are recognized risk factors for cardiovascular disease. We tested the hypothesis that the cumulative effects of common genetic variants for lipids are collectively associated with subclinical atherosclerosis and incident coronary heart disease. APPROACH AND RESULTS:Participants were drawn from the Erasmus Rucphen Family Study (n=2269) and the Rotterdam Study (n=8130). Linear regression and Cox proportional hazards models were applied to assess the influence of 4 risk scores derived from common genetic variants for lipids (total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglycerides) on carotid plaque, intima-media thickness, incident myocardial infarction, and coronary heart disease. Adjusted for age and sex, all 4 risk scores were associated with carotid plaque. This relationship was the strongest for the LDL-C score, which increased plaque score by 0.102 per SD increase in genetic risk score (P=3.2 × 10(-8)). The LDL-C score was also nominally associated with intima-media thickness, which increased 0.006 mm per SD increase in score (P=0.05). Both the total cholesterol and LDL-C scores were associated with incident myocardial infarction and coronary heart disease with hazard ratios between 1.10 and 1.13 per SD increase in score. Inclusion of additional risk factors as covariates minimally affected these results. CONCLUSIONS: Common genetic variants with small effects on lipid levels are, in combination, significantly associated with subclinical and clinical cardiovascular outcomes. As knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events.
Authors: Rector Arya; Agustin Escalante; Vidya S Farook; Jose F Restrepo; Daniel F Battafarano; Marcio Almeida; Mark Z Kos; Marcel J Fourcaudot; Srinivas Mummidi; Satish Kumar; Joanne E Curran; Christopher P Jenkinson; John Blangero; Ravindranath Duggirala; Inmaculada Del Rincon Journal: Atherosclerosis Date: 2017-11-26 Impact factor: 5.162
Authors: Gagandeep Kaur Walia; Vipin Gupta; Aastha Aggarwal; Mohammad Asghar; Frank Dudbridge; Nicholas Timpson; Nongmaithem Suraj Singh; M Ravi Kumar; Sanjay Kinra; Dorairaj Prabhakaran; K Srinath Reddy; Giriraj Ratan Chandak; George Davey Smith; Shah Ebrahim Journal: PLoS One Date: 2014-07-03 Impact factor: 3.240
Authors: Caroline J Bull; Carolina Bonilla; Jeff M P Holly; Claire M Perks; Neil Davies; Philip Haycock; Oriana Hoi Yun Yu; J Brent Richards; Rosalind Eeles; Doug Easton; Zsofia Kote-Jarai; Ali Amin Al Olama; Sara Benlloch; Kenneth Muir; Graham G Giles; Robert J MacInnis; Fredrik Wiklund; Henrik Gronberg; Christopher A Haiman; Johanna Schleutker; Børge G Nordestgaard; Ruth C Travis; David Neal; Nora Pashayan; Kay-Tee Khaw; Janet L Stanford; William J Blot; Stephen Thibodeau; Christiane Maier; Adam S Kibel; Cezary Cybulski; Lisa Cannon-Albright; Hermann Brenner; Jong Park; Radka Kaneva; Jyotsna Batra; Manuel R Teixeira; Agnieszka Micheal; Hardev Pandha; George Davey Smith; Sarah J Lewis; Richard M Martin Journal: Cancer Med Date: 2016-03-19 Impact factor: 4.452