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Heritabilities, apolipoprotein E, and effects of inbreeding on plasma lipids in a genetically isolated population: the Erasmus Rucphen Family Study.


ABSTRACT: Despite considerable progress in unravelling the genetic basis of dyslipidemias, most findings are based on families with extreme phenotypes. We studied lipid levels in an extended pedigree ascertained irrespective of phenotype from the population of a recent genetic isolate in the Netherlands. Heritabilities of plasma lipid measures were examined; this analysis also included estimates of the proportion of variance attributable to ApoE genotype. The association between inbreeding and lipids was also considered, as a substantial fraction of the population had known inbreeding. A total of 868 individuals from this pedigree, containing more than 60,000 people over 15 generations, were investigated in this study. Laboratory analysis of these subjects included the determination of fasting plasma lipids. ApoE epsilon2/3/4 status was ascertained using TaqMan assays. Heritabilities for plasma lipids were estimated with adjustments for multiple covariates using SOLAR. Heritabilities for total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), TC/HDL ratio, and TG/HDL ratio were found to be 0.35, 0.56, 0.30, 0.24, 0.49, and 0.39, respectively. The addition of ApoE genotype in the model significantly decreased these estimates (Deltah(2) = -0.030, -0.004, -0.054, and -0.006 for TC, HDL, LDL, and TG). In a further analysis, TC and LDL were positively associated with the extent of inbreeding (p (trend) = 0.02 and p (trend) = 0.05, respectively). These data provide estimates of lipid heritability unbiased due to selection and suggest that this population represents a good opportunity to localize novel genes influencing plasma lipid levels.

SUBMITTER: Isaacs A 

PROVIDER: S-EPMC2797851 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Heritabilities, apolipoprotein E, and effects of inbreeding on plasma lipids in a genetically isolated population: the Erasmus Rucphen Family Study.

Isaacs Aaron A   Sayed-Tabatabaei Fakhredin A FA   Aulchenko Yurii S YS   Zillikens M Carola MC   Sijbrands Eric J G EJ   Schut Anna F C AF   Rutten Wim P F WP   Pols Huibert A P HA   Witteman Jacqueline C M JC   Oostra Ben A BA   van Duijn Cornelia M CM  

European journal of epidemiology 20070221 2


Despite considerable progress in unravelling the genetic basis of dyslipidemias, most findings are based on families with extreme phenotypes. We studied lipid levels in an extended pedigree ascertained irrespective of phenotype from the population of a recent genetic isolate in the Netherlands. Heritabilities of plasma lipid measures were examined; this analysis also included estimates of the proportion of variance attributable to ApoE genotype. The association between inbreeding and lipids was  ...[more]

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