Genome-wide linkage analysis replicates susceptibility locus for fasting plasma triglycerides: NHLBI Family Heart Study

Donna K. Arnett, Michael B. Miller, Hilary Coon, R. Curtis Ellison, Kari E. North, Michael Province, Mark Leppert, John H. Eckfeldt

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Recent reports implicate chromosomal regions linked to inter-individual variation in plasma triglycerides. We conducted genome-wide scans to replicate these linkages and/or identify other loci influencing plasma triglycerides in the NHLBI Family Heart Study (FHS). Data were obtained for 501 three-generational families. Genotyping was done by the Utah Molecular Genetics Laboratory and NHLBI Mammalian Genotyping Service; markers from both were placed on one genetic map. Analysis was done using multipoint variance components linkage. Fasting plasma triglycerides were log-transformed and age-, sex-, and field center-adjusted; suggestive linkage evidence was found on chromosome 8 (LOD=2.80 at 89 cM, marker D8S1141). Further adjustment for waist girth, BMI, diabetes, hypertension, and lipid-lowering drugs suggested linkage regions on chromosomes 6 (LOD=2.29 at 79 cM, marker D6S295) and 15 (LOD=1.85 at 43 cM, marker D15S659). Since HDL is correlated with triglycerides and because it was linked to this region on chromosome 15 in FHS, we created a composite triglyceride-HDL phenotype. The combined phenotype LOD score was 3.0 at the same marker on chromosome 15. Chromosome 15 likely harbors a susceptibility locus with an influence on triglycerides and HDL. Regions on chromosomes 6 and 8 may also contain loci contributing to inter-individual variation in plasma triglycerides.

Original languageEnglish (US)
Pages (from-to)468-474
Number of pages7
JournalHuman Genetics
Volume115
Issue number6
DOIs
StatePublished - 2004

Bibliographical note

Funding Information:
Acknowledgements Support was partially provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, U01 HL56569. This paper is presented on behalf of the investigators of the NHLBI FHS. Participating institutions and principal staff of the study not participating as authors are as follows: Forsyth County/University of North Carolina/Wake Forest University: Gerardo Heiss, Stephen Rich, Greg Evans, H.A. Tyroler, and Amy Haire; University of Minnesota Field Center: James Pankow, James Peacock, and Greg Feitl; Boston University Framingham Field Center: Richard H. Myers, Yuqing Zhang, Andrew G. Bostom, Luc Djoussé, Jemma B. Wilk, and Greta Lee Splansky; University of Utah Field Center: Steven C. Hunt, Roger R. Williams (deceased), Paul N. Hopkins, and Jan Skuppin; Coordinating Center, Washington University, St. Louis: D.C. Rao, Ingrid B. Borecki, Mary Feitosa, Jeanne Cashman, and Avril Adelman; University of Minnesota Central Biochemistry Laboratory: Catherine Leiendecker-Foster, Michael Y. Tsai, and Greg Rynders; University of Utah Central Molecular Laboratory: Mark F. Leppert, Jean-Marc Lalouel, Tena Varvil, Lisa Baird; National Heart, Lung, & Blood Institute—Project Office: Phyliss Sholinsky, Millicent Higgins (retired), Jacob Keller (retired), Sarah Knox, and Lorraine Silsbee.

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