title: Multilocus heterozygosity and coronary heart disease: nested case-control studies in men and women.
abstract: BACKGROUND
  Generalized allelic heterozygosity has been proposed to improve reproductive fitness and has been associated with higher blood pressure, but its association with chronic disease is not well characterized.
  
  
  METHODS
  Using the Affymetrix Genome-Wide Human 6.0 array, we performed whole genome scans in parallel case-control studies of coronary heart disease (CHD) nested in the Health Professionals Follow-up Study and Nurses' Health Study. We examined ~700,000 single nucleotide polymorphisms (SNPs) in 435 men with incident CHD and 878 matched controls and 435 women with incident CHD with 931 matched controls. We examined the relationship of genome-wide heterozygosity with risk of incident of CHD and with baseline levels of cardiovascular risk factors.
  
  
  RESULTS
  In both cohorts, approximately 227650 (SD 2000) SNPs were heterozygous. The number of heterozygous SNPs was not related to risk of CHD in either men or women (adjusted odds ratios per 2000 heterozygous SNPs 1.01 [95% confidence interval, 0.91-1.13] in women and 0.94 [0.84-1.06] in men). We also found no consistent associations of genome-wide heterozygosity with levels of lipids, inflammatory markers, adhesion molecules, homocysteine, adiponectin, or body-mass index.
  
  
  CONCLUSIONS
  In these parallel nested case-control studies, we found no relationship of multilocus heterozygosity with risk of CHD or its major risk factors. Studies in other populations are needed to rule out associations with lower levels of heterozygosity.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
authors.affiliation: Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark; Division of Genetics, Children's Hospital, Boston, Massachusetts, United States of America; Division of Endocrinology, Children's Hospital, Boston, Massachusetts, United States of America; Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America; Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Tune H
authors.initials: TH
authors.lastname: Pers
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Pai
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood / Q000235:genetics; D003327:Coronary Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006282:Health Personnel; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008055:Lipids; D006710:Homocysteine