A family-specific linkage analysis of blood lipid response to fenofibrate in the Genetics of Lipid Lowering Drug and Diet Network. Issue 10 (October 2015)

• Record Type: Journal Article
• Authors: Hidalgo, Bertha; Aslibekyan, Stella; Wiener, Howard W.; Irvin, Marguerite R.; Straka, Robert J.; Borecki, Ingrid B.; Tiwari, Hemant K.; Tsai, Michael Y.; Hopkins, Paul N.; Ordovas, Jose M.; Arnett, Donna K.
• Is Part Of: Pharmaocogenetics and genomics. Volume 25:Issue 10(2015:Oct.)
• Publication Date: 2015-10
• Subjects: Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000162
• Languages: English
• ISSNs: 1744-6872

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>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 (<italic>n</italic>=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 (<italic>N</italic>=19), we observed a peak logarithm of odds score of 5.17 for chromosome 7. Two genes under this peak (<italic>ABCB4</italic> and <italic>CD36</italic>) 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.</p> </sec> </abstract>