title: Use of systems biology approaches to analysis of genome-wide association studies of myocardial infarction and blood cholesterol in the nurses' health study and health professionals' follow-up study.
abstract: With the advance of genome-wide association studies and newly identified SNP (single-nucleotide polymorphism) associations with complex disease, important discoveries have emerged focusing not only on individual genes but on disease-associated pathways and gene sets. The authors used prospective myocardial infarction case-control studies nested in the Nurses' Health and Health Professionals Follow-Up Studies to investigate genetic variants associated with myocardial infarction or LDL, HDL, triglycerides, adiponectin and apolipoprotein B (apoB). Using these case-control studies to illustrate an integrative systems biology approach, the authors applied SNP set enrichment analysis to identify gene sets where expression SNPs representing genes from these sets show enrichment in their association with endpoints of interest. The authors also explored an aggregate score approach. While power limited one's ability to detect significance for association of individual loci with myocardial infarction, the authors found significance for loci associated with LDL, HDL, apoB and triglycerides, replicating previous observations. Applying SNP set enrichment analysis and risk score methods, the authors also found significance for three gene sets and for aggregate scores associated with myocardial infarction as well as for loci-related to cardiovascular risk factors, supporting the use of these methods in practice.
authors.affiliation: Department of Molecular Profiling and Research informatics, Merck Research Laboratories, Merck & Co., Inc., Whitehouse Station, New Jersey, United States of America.
authors.forename: Dermot
authors.initials: D
authors.lastname: Reilly
authors.affiliation: Department of Molecular Profiling and Research informatics, Merck Research Laboratories, Merck & Co., Inc., Whitehouse Station, New Jersey, United States of America.
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
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: Department of Epidemiology, Merck Research Laboratories, Merck & Co., Inc., Whitehouse Station, New Jersey, United States of America.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Girman
authors.affiliation: Channing Division of Network Medicine, Department of Epidemiology and Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America ; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 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; D005260:Female; D005500:Follow-Up Studies; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D009726:Nurses; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D049490:Systems Biology; D014280:Triglycerides / Q000097:blood / Q000235:genetics
chemical_list: D052242:Adiponectin; D008074:Lipoproteins; D014280:Triglycerides