title: A novel quantitative trait locus on chromosome 1 with pleiotropic effects on HDL-cholesterol and LDL particle size in hypertensive sibships.
abstract: BACKGROUND
  High-density lipoprotein (HDL)-cholesterol, triglycerides, and LDL particle size are correlated lipid traits. Abnormal levels of these traits are frequent in hypertensive individuals and contribute to increased risk of coronary heart disease (CHD). We performed univariate and bivariate linkage analyses to identify genomic regions that influence levels of these traits and exert pleiotropic effects on the traits in hypertensive sibships.
  
  
  METHODS
  Subjects included 691 non-Hispanic white individuals (mean age 63.1+/-8.5 years, 57% women, 78% hypertensive) ascertained through sibships with two or more individuals diagnosed with hypertension before age 60 years. The LDL particle size was measured by polyacrylamide gel electrophoresis and triglycerides were log-transformed to reduce skewness. Genotypes were measured at 366 microsatellite marker loci distributed across the 22 autosomes. Univariate and bivariate linkage analyses were performed using a variance components approach.
  
  
  RESULTS
  Significant (P < .001) genetic correlations were confirmed for all pairwise combinations of the traits. Univariate linkage analyses demonstrated evidence of linkage (defined as multipoint LOD scores > or =1.3) for HDL-cholesterol on chromosomes 1p, 3p, 9q, and 18q; for log triglycerides on chromosome 10q; and for LDL particle size on chromosomes 2p and 8p. Pairwise bivariate linkage analyses of the three traits revealed a region with pleiotropic effects on HDL-cholesterol and LDL particle size on chromosome 1p (LOD score 4.48).
  
  
  CONCLUSIONS
  These findings indicate the presence of a quantitative trait locus on chromosome 1 that has pleiotropic effects on HDL-cholesterol and LDL particle size and may therefore influence CHD susceptibility in hypertensive sibships.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN 55905, USA. kullo.iftikhar@mayo.edu
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
mesh_terms: D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood* / Q000737:chemistry; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D040641:Quantitative Trait Loci / Q000235:genetics*; D035781:Siblings; D013223:Statistics as Topic; D014280:Triglycerides / Q000097:blood / Q000737:chemistry
chemical_list: D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides