title: Influence of common genetic variation on blood lipid levels, cardiovascular risk, and coronary events in two British prospective cohort studies.
abstract: OBJECTIVE
  The aim of this study was to quantify the collective effect of common lipid-associated single nucleotide polymorphisms (SNPs) on blood lipid levels, cardiovascular risk, use of lipid-lowering medication, and risk of coronary heart disease (CHD) events.
  
  
  RESULTS
  Analysis was performed in two prospective cohorts: Whitehall II (WHII; N = 5059) and the British Women's Heart and Health Study (BWHHS; N = 3414). For each participant, scores were calculated based on the cumulative effect of multiple genetic variants influencing total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Compared with the bottom quintile, individuals in the top quintile of the LDL-C genetic score distribution had higher LDL-C {mean difference of 0.85 [95% confidence interval, (CI) = 0.76-0.94] and 0.63 [95% CI = 0.50-0.76] mmol/l in WHII and BWHHS, respectively}. They also tended to have greater odds of having 'high-risk' status (Framingham 10-year cardiovascular disease risk >20%) [WHII: odds ratio (OR) = 1.36 (0.93-1.98), BWHHS: OR = 1.49 (1.14-1.94)]; receiving lipid-lowering treatment [WHII: OR = 2.38 (1.57-3.59), BWHHS: OR = 2.24 (1.52-3.29)]; and CHD events [WHII: OR = 1.43 (1.02-2.00), BWHHS: OR = 1.31 (0.99-1.72)]. Similar associations were observed for the TC score in both studies. The TG score was associated with high-risk status and medication use in both studies. Neither HDL nor TG scores were associated with the risk of coronary events. The genetic scores did not improve discrimination over the Framingham risk score.
  
  
  CONCLUSIONS
  At the population level, common SNPs associated with LDL-C and TC contribute to blood lipid variation, cardiovascular risk, use of lipid-lowering medications and coronary events. However, their effects are too small to discriminate future lipid-lowering medication requirements or coronary events.
authors.affiliation: Department of Genetics, Environment and Evolution, University College London Genetics Institute, Gower St, London WC1E 6BT, UK.
authors.forename: Sonia
authors.initials: S
authors.lastname: Shah
authors.forename: Juan P
authors.initials: JP
authors.lastname: Casas
authors.forename: Tom R
authors.initials: TR
authors.lastname: Gaunt
authors.forename: Jackie
authors.initials: J
authors.lastname: Cooper
authors.forename: Fotios
authors.initials: F
authors.lastname: Drenos
authors.forename: Delilah
authors.initials: D
authors.lastname: Zabaneh
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Swerdlow
authors.forename: Tina
authors.initials: T
authors.lastname: Shah
authors.forename: Reecha
authors.initials: R
authors.lastname: Sofat
authors.forename: Jutta
authors.initials: J
authors.lastname: Palmen
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.forename: Shah
authors.initials: S
authors.lastname: Ebrahim
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: John
authors.initials: J
authors.lastname: Whittaker
authors.forename: Ian N M
authors.initials: IN
authors.lastname: Day
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000235:genetics*; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism; D008078:Cholesterol, LDL / Q000235:genetics / Q000378:metabolism; D003327:Coronary Disease / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014280:Triglycerides