title: A family-specific linkage analysis of blood lipid response to fenofibrate in the Genetics of Lipid Lowering Drug and Diet Network.
abstract: Cost-effective identification of novel pharmacogenetic variants remains a pressing need in the field. Using data from the Genetics of Lipid Lowering Drugs and Diet Network, we identified genomic regions of relevance to fenofibrate response in a sample of 173 families. Our approach included a multipoint linkage scan, followed by selection of the families showing evidence of linkage. We identified a strong signal for changes in LDL-cholesterol (LDL-C) on chromosome 7 (peak logarithm of odds score = 4.76) in the full sample (n = 821). The signal for LDL-C response remained even after adjusting for baseline LDL-C. Restricting analyses only to the families contributing to the linkage signal for LDL-C (N = 19), we observed a peak logarithm of odds score of 5.17 for chromosome 7. Two genes under this peak (ABCB4 and CD36) were of biological interest. These results suggest that linked family analyses might be a useful approach to gene discovery in the presence of a complex (e.g. multigenic) phenotype.
authors.affiliation: Departments of aEpidemiology bBiostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama cDepartment of Experimental and Clinical Pharmacology, College of Pharmacy dDepartment of Medicine and Pathology, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota eJean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Medford, Massachusetts fDivision of Statistical Genomics, Genome Sciences Center, Washington University School of Medicine, Seattle, Washington gDepartment of Internal Medicine, Division of Cardiovascular Genetics, School of Medicine, University of Utah, Salt Lake City, Utah, USA hDepartment of Epidemiology, Atherothrombosis and Imaging, Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Instituto Madrileño de Estudios Avanzados (IMDEA) Alimentacion, Madrid, Spain.
authors.forename: Bertha
authors.initials: B
authors.lastname: Hidalgo
authors.forename: Stella
authors.initials: S
authors.lastname: Aslibekyan
authors.forename: Howard W
authors.initials: HW
authors.lastname: Wiener
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Irvin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Straka
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D004032:Diet; D005190:Family; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D008040:Genetic Linkage; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008126:Lod Score; D008297:Male; D008875:Middle Aged
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids; D011345:Fenofibrate