Evidence for a QTL on chromosome 19 influencing LDL cholesterol levels in the general population
article
The genetic basis of cardiovascular disease (CVD) with its complex etiology is still largely elusive. Plasma levels of lipids and apolipoproteins are among the major quantitative risk factors for CVD and are well-established intermediate traits that may be more accessible to genetic dissection than clinical CVD end points. Chromosome 19 harbors multiple genes that have been suggested to play a role in lipid metabolism and previous studies indicated the presence of a quantitative trait locus (QTL) for cholesterol levels in genetic isolates. To establish the relevance of genetic variation at chromosome 19 for plasma levels of lipids and apolipoproteins in the general, out-bred Caucasian population, we performed a linkage study in four independent samples, including adolescent Dutch twins and adult Dutch, Swedish and Australian twins totaling 493 dizygotic twin pairs. The average spacing of short-tandem-repeat markers was 6-8 cM. In the three adult twin samples, we found consistent evidence for linkage of chromosome 19 with LDL cholesterol levels (maximum LOD scores of 4.5, 1.7 and 2.1 in the Dutch, Swedish and Australian sample, respectively); no indication for linkage was observed in the adolescent Dutch twin sample. The QTL effects in the three adult samples were not significantly different and a simultaneous analysis of the samples increased the maximum LOD score to 5.7 at 60 cM pter. Bivariate analyses indicated that the putative LDL-C QTL also contributed to the variance in ApoB levels, consistent with the high genetic correlation between these phenotypes. Our study provides strong evidence for the presence of a QTL on chromosome 19 with a major effect on LDL-C plasma levels in outbred Caucasian populations.
Topics
Cardiovascular risk factorsLinkageQuantitative trait locus (QTL)Twin pairsApolipoproteinLipidLow density lipoprotein cholesterolAustraliaCardiovascular riskCaucasianCholesterol blood levelChromosome 19Controlled studyDizygotic twinsGenetic correlationGenetic linkageGenetic variabilityLipid blood levelLipid metabolismMajor clinical studyNetherlandsPhenotypePopulation researchQuantitative analysisQuantitative trait locusRisk factorScoring systemSwedenTandem repeatAdolescentAdultAgedCardiovascular DiseasesCholesterol, LDLChromosomes, Human, Pair 19European Continental Ancestry GroupFemaleGene FrequencyGenetic MarkersGenetics, PopulationHumansLinkage (Genetics)Lod ScoreMaleMiddle AgedPhenotypeQuantitative Trait LociTwins, DizygoticVariation (Genetics)
TNO Identifier
237336
ISSN
10184813
Source
European Journal of Human Genetics, 11(11), pp. 845-850.
Pages
845-850
Files
To receive the publication files, please send an e-mail request to TNO Repository.