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| PMID |
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| TITLE |
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| Meta-analysis of four new genome scans for lipid parameters and analysis of positional candidates in positive linkage regions. |
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| ABSTRACT |
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| 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| pubmed |
2005/07/15 09:00 |
| medline |
2005/11/09 09:00 |
| entrez |
2005/07/15 09:00 |
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| 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 |
Daniëlle |
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 |
|
|
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| INVESTIGATORS |
|
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| JOURNAL |
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| 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 |
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| MEDLINETA: Eur J Hum Genet |
| COUNTRY: England |
| ISSNLINKING: 1018-4813 |
| NLMUNIQUEID: 9302235 |
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| PUBLICATION TYPE |
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| 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 |
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| COMMENTS AND CORRECTIONS |
|
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| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| AG04563 |
NIA NIH HHS |
United States |
| AG10175 |
NIA NIH HHS |
United States |
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| GENERAL NOTE |
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| KEYWORDS |
|
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| MESH HEADINGS |
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| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
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| 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 |
|
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| GENE SYMBOLS |
|
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| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Apolipoprotein A-I |
| 0 |
Apolipoproteins B |
| 0 |
Cholesterol, HDL |
| 0 |
Cholesterol, LDL |
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| OTHER ID's |
|
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|
