title: Relative contributions of genes, environment, and interactions to blood lipid concentrations in a general adult population.
abstract: The authors evaluated the contributions of nine genetic (G) variants (selected from 275 single nucleotide polymorphisms in 11 reverse cholesterol transport pathway genes), five environmental (E) factors (selected from 10), and G x G, E x E, and G x E interactions in explaining population variance of blood lipid concentrations. Total cholesterol, triglycerides, and high density lipoprotein (HDL) cholesterol were measured, and low density lipoprotein (LDL) cholesterol and HDL cholesterol/LDL cholesterol ratio were calculated in a population-based random sample of 1,543 men and women in Geneva, Switzerland, aged 35-74 years in 1999-2001. Explained variances (R2) for HDL cholesterol/LDL cholesterol ratio, HDL cholesterol, and LDL cholesterol, respectively, were 34%, 33%, and 19%, decomposed into main effects of G (6%, 4%, and 5%) and E (25%, 28%, and 11%), with just 3%, 2%, and 3% due to G x G, E x E, and G x E interactions, respectively. Risk factor clustering was only moderate: 70% of study subjects had < or =3 variants, 75% had < or =2 environmental exposures, and 69% had < or =5 of both types of factors. Multiple genes with weak associations, together with more dominating environmental factors, are involved in determining blood lipid concentrations. Interactions added little explained variance. Increasing trends in hypercholesterolemia are attributable to environmental changes affecting populations as a whole. Reducing obesity and smoking and moderating alcohol intake in entire populations should remain the primary strategies for lipid control.
authors.affiliation: Division of Clinical Epidemiology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Costanza
authors.forename: Eftihia
authors.initials: E
authors.lastname: Cayanis
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Ross
authors.forename: Maria Sol
authors.initials: MS
authors.lastname: Flaherty
authors.forename: Gabriela B
authors.initials: GB
authors.lastname: Alvin
authors.forename: Kamna
authors.initials: K
authors.lastname: Das
authors.forename: Alfredo
authors.initials: A
authors.lastname: Morabia
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D004522:Educational Status; D004777:Environment; D005260:Female; D006801:Humans; D008019:Life Style; D008055:Lipids / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000097:blood; D011795:Surveys and Questionnaires; D013557:Switzerland; D014280:Triglycerides / Q000097:blood / Q000235:genetics
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; D008055:Lipids; D014280:Triglycerides