Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
14571269
TITLE
Evidence for a QTL on chromosome 19 influencing LDL cholesterol levels in the general population.
ABSTRACT
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.
DATE PUBLISHED
2003 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2003/10/23 05:00
medline 2004/06/24 05:00
entrez 2003/10/23 05:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Beekman M Beekman Marian M Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. M.Beekman@lumc.nl
Heijmans BT Heijmans Bastiaan T BT
Martin NG Martin Nicholas G NG
Whitfield JB Whitfield John B JB
Pedersen NL Pedersen Nancy L NL
DeFaire U DeFaire Ulf U
Snieder H Snieder Harold H
Lakenberg N Lakenberg Nico N
Suchiman HE Suchiman H Eka D HE
de Knijff P de Knijff Peter P
Frants RR Frants Rune R RR
van Ommen GJ van Ommen Gert Jan B GJ
Kluft C Kluft Cornelis C
Vogler GP Vogler George P GP
Boomsma DI Boomsma Dorret I DI
Slagboom PE Slagboom P Eline PE
INVESTIGATORS
JOURNAL
VOLUME: 11
ISSUE: 11
TITLE: European journal of human genetics : EJHG
ISOABBREVIATION: Eur. J. Hum. Genet.
YEAR: 2003
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 1018-4813
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Eur J Hum Genet
COUNTRY: England
ISSNLINKING: 1018-4813
NLMUNIQUEID: 9302235
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
AG04563 NIA NIH HHS United States
AG10175 NIA NIH HHS United States
HL55976 NHLBI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Cardiovascular Diseases genetics
Cholesterol, LDL genetics
Chromosomes, Human, Pair 19 genetics
European Continental Ancestry Group genetics
Female genetics
Gene Frequency genetics
Genetic Linkage genetics
Genetic Markers genetics
Genetic Variation genetics
Genetics, Population genetics
Humans genetics
Lod Score genetics
Male genetics
Middle Aged genetics
Phenotype genetics
Quantitative Trait Loci genetics
Twins, Dizygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Cholesterol, LDL
0 Genetic Markers
OTHER ID's