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.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
16015283
TITLE
Meta-analysis of four new genome scans for lipid parameters and analysis of positional candidates in positive linkage regions.
ABSTRACT
Lipid levels in plasma strongly influence the risk for coronary heart disease. To localise and subsequently identify genes affecting lipid levels, we performed four genome-wide linkage scans followed by combined linkage/association analysis. Genome-scans were performed in 701 dizygotic twin pairs from four samples with data on plasma levels of HDL- and LDL-cholesterol and their major protein constituents, apolipoprotein AI (ApoAI) and Apolipoprotein B (ApoB). To maximise power, the genome scans were analysed simultaneously using a well-established meta-analysis method that was newly applied to linkage analysis. Overall LOD scores were estimated using the means of the sample-specific quantitative trait locus (QTL) effects inversely weighted by the standard errors obtained using an inverse regression method. Possible heterogeneity was accounted for with a random effects model. Suggestive linkage for HDL-C was observed on 8p23.1 and 12q21.2 and for ApoAI on 1q21.3. For LDL-C and ApoB, linkage regions frequently coincided (2p24.1, 2q32.1, 19p13.2 and 19q13.31). Six of the putative QTLs replicated previous findings. After fine mapping, three maximum LOD scores mapped within 1 cM of major candidate genes, namely APOB (LOD=2.1), LDLR (LOD=1.9) and APOE (LOD=1.7). APOB haplotypes explained 27% of the QTL effect observed for LDL-C on 2p24.1 and reduced the LOD-score by 0.82. Accounting for the effect of the LDLR and APOE haplotypes did not change the LOD score close to the LDLR gene but abolished the linkage signal at the APOE gene. In conclusion, application of a new meta-analysis approach maximised the power to detect QTLs for lipid levels and improved the precision of their location estimate.
DATE PUBLISHED
2005 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2005/07/15 09:00
medline 2005/11/09 09:00
entrez 2005/07/15 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Heijmans BT Heijmans Bastiaan T BT Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands. b.t.heijmans@lumc.nl
Beekman M Beekman Marian M
Putter H Putter Hein H
Lakenberg N Lakenberg Nico N
van der Wijk HJ van der Wijk Henk Jan HJ
Whitfield JB Whitfield John B JB
Posthuma D Posthuma Daniƫlle D
Pedersen NL Pedersen Nancy L NL
Martin NG Martin Nicholas G NG
Boomsma DI Boomsma Dorret I DI
Slagboom PE Slagboom P Eline PE
INVESTIGATORS
JOURNAL
VOLUME: 13
ISSUE: 10
TITLE: European journal of human genetics : EJHG
ISOABBREVIATION: Eur. J. Hum. Genet.
YEAR: 2005
MONTH: Oct
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
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Twin Study
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
AG04563 NIA NIH HHS United States
AG10175 NIA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Apolipoprotein A-I blood
Apolipoproteins B blood
Australia blood
Cholesterol, HDL blood
Cholesterol, LDL blood
Chromosome Mapping methods
Female methods
Genome, Human methods
Humans methods
Lod Score methods
Male methods
Middle Aged methods
Netherlands methods
Quantitative Trait Loci methods
Sweden methods
Twins, Dizygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Apolipoprotein A-I
0 Apolipoproteins B
0 Cholesterol, HDL
0 Cholesterol, LDL
OTHER ID's