RÉSUMÉ
Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Sujet(s)
Exercice physique , Locus génétiques/génétique , Lipides/sang , Lipides/génétique , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Asiatiques/génétique , 38410/génétique , Brésil , Protéines de liaison au calcium/génétique , Cholestérol/sang , Cholestérol HDL/sang , Cholestérol HDL/génétique , Cholestérol LDL/sang , Cholestérol LDL/génétique , Femelle , Étude d'association pangénomique , Génotype , Hispanique ou Latino/génétique , Humains , Protéines à homéodomaine LIM/génétique , Métabolisme lipidique/génétique , Mâle , Protéines membranaires/génétique , Protéines associées aux microtubules/génétique , Adulte d'âge moyen , Protéines du muscle/génétique , Protéines de tissu nerveux/génétique , Facteurs de transcription/génétique , Triglycéride/sang , Triglycéride/génétique , 38413/génétique , Jeune adulteRÉSUMÉ
Summary measures of cardiovascular risk have long been used in public health, but few include nutritional predictors despite extensive evidence linking diet and heart disease. Study objectives were to develop and validate a novel risk score in a case-control study of myocardial infarction (MI) conducted in Costa Rica during 1994-2004. After restricting the data set to healthy participants (n = 1678), conditional logistic regression analyses modeled associations of lifestyle factors (unhealthy diet, decreased physical activity, smoking, waist:hip ratio, low or high alcohol intake, and low socioeconomic status) with risk for MI. Using the estimated coefficients as weights for each component, a regression model was fit to assess score performance. The score was subsequently validated in participants with a history of chronic disease. Higher risk score values were associated with a significantly increased risk of MI [OR = 2.72 (95% CI = 2.28-3.24)]. The findings were replicated in a model (n = 1392) that included the best covariate measures available in the study [OR = 2.71 (95% CI = 2.26-3.26)]. Performance of the score in different subsets of the study population showed c-statistics ranging from 0.63 to 0.67. The new score presents a quantitative summary of modifiable cardiovascular risk factors in the study population.