title: Genetic loci for serum lipid fractions and intracerebral hemorrhage.
abstract: BACKGROUND
  Serum total cholesterol and its fractions are inversely associated with intracerebral hemorrhages (ICH) and their potential subclinical precursor, cerebral microbleeds. To ascertain whether there is a genetic basis for this inverse association, we studied established genetic loci for serum total, LDL, and HDL cholesterol, and triglycerides in their association with ICH and microbleeds.
  
  
  METHODS
  Data on 161 genetic variants for serum lipids was collected in 9011 stroke-free participants (mean age 65.8, SD 10.2; 57.9% women) of the population-based Rotterdam Study. Participants were followed from baseline (1997-2005) up to 2013 for the occurrence of ICH. A subset of 4179 participants underwent brain MRI for microbleed assessment between 2005 and 2011. We computed genetic risk scores (GRS) for the joint effect of lipid variants. Cox proportional hazards and logistic regression models were used to investigate the association of GRS of lipid fractions with ICH and microbleeds.
  
  
  RESULTS
  After a mean follow-up of 8.7 (SD 4.1) years, 67 (0.7%) participants suffered an ICH. Microbleed prevalence was 19.6%. Higher genetic load for high serum total and LDL cholesterol was associated with an increased risk of ICH. Higher genetic load for high serum LDL cholesterol was borderline associated with a higher prevalence of multiple lobar microbleeds.
  
  
  CONCLUSIONS
  Genetic susceptibility for high serum total and LDL cholesterol is positively associated with incident ICH and borderline associated with multiple lobar microbleeds. We did not find a genetic basis for the previously reported inverse association between serum lipid levels and ICH.
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: Saloua
authors.initials: S
authors.lastname: Akoudad
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: Marileen L P
authors.initials: ML
authors.lastname: Portegies
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: Hieab H
authors.initials: HH
authors.lastname: Adams
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bos
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Neurology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koudstaal
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Radiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. Electronic address: m.vernooij@erasmusmc.nl.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002543:Cerebral Hemorrhage / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D010641:Phenotype; D015995:Prevalence; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides
keywords: Cerebral microbleeds; Epidemiology; Genetics; Intracerebral hemorrhages; Lipids