Genome-wide linkage analysis replicates susceptibility locus for fasting plasma triglycerides: NHLBI Family Heart Study.
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.
Arnett
Donna K
DK
Division of Epidemiology, University of Minnesota, 1300 South Second Street, Suite 300, Minneapolis, MN 55454, USA. arnett@epi.umn.edu
Miller
Michael B
MB
Coon
Hilary
H
Ellison
R Curtis
RC
North
Kari E
KE
Province
Michael
M
Leppert
Mark
M
Eckfeldt
John H
JH
D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure; D002884:Chromosomes, Human, Pair 15; D002896:Chromosomes, Human, Pair 6; D002898:Chromosomes, Human, Pair 8; D005192:Family Health; D005215:Fasting; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008075:Lipoproteins, HDL / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D008126:Lod Score; D008297:Male; D010641:Phenotype; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000097:blood* / Q000235:genetics*
D005819:Genetic Markers; C034396:HDL-triglyceride; D008075:Lipoproteins, HDL; D014280:Triglycerides