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
19016617
TITLE
Linkage and association analyses of longitudinally measured lipid phenotypes in adolescence.
ABSTRACT
The genetic basis of cardiovascular disease (CVD) is complex and still largely elusive. Plasma lipid concentrations are well-established risk factors for cardiovascular disease (CVD), and have adult heritabilities ranging from 0.48 to 0.87. Estimates for adolescents are slightly higher (range 0.71 to 0.82). To identify loci affecting lipid concentrations across adolescence, we analyzed longitudinal lipid data in a sample of 134 monozygotic and 626 dizygotic twin pairs at ages twelve, fourteen and sixteen, and their siblings, from 760 Australian families. Univariate linkage analysis for each phenotype and time point was supplemented by multivariate analysis across the time points. A genome-wide association scan was also performed on a subset of the subjects (N = 441). The strongest linkage was seen for triglycerides on chromosome 6p24.3 (multivariate -log(10) p = 6.81; equivalent LOD = 6.13; p = 1.55 x 10(-7)). Significant linkage was also found for LDL cholesterol on chromosome 2q35 (multivariate -log(10)p = 5.59; equivalent LOD = 4.53; p = 2.57 x 10(-6)). In the association analysis, rs10503840 on 8p21.1 was significantly associated with total cholesterol levels at age fourteen (p = 8.24 x 10(-7), estimated significance threshold 2.45 x 10(-6)). Association at p < 2.25 x 10(-6) was also found between triglycerides at age 12 and rs10507266, in an intron of THRAP2 (MIM 608771) on 12q24.21; and between HDL-C at age 14 and rs10506325 in an intergenic region of 12q13.13. Suggestive evidence of association at ages twelve and fourteen was found between HDL-C and rs10492859 on 16q23 (p = 2.42 x 10(-5) and 2.77 x 10(-4), respectively). Further longitudinal genetic studies of cardiovascular risk factors, focused on critical periods of development or change, are needed.
DATE PUBLISHED
2008 Dec
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2008/11/20 09:00
medline 2009/05/01 09:00
entrez 2008/11/20 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Middelberg RP Middelberg Rita P RP Genetic Epidemiology Unit, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Australia. rita.middelberg@qimr.edu.au
Gordon SD Gordon Scott D SD
Zhu G Zhu Gu G
McRae A McRae Allan A
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Whitfield JB Whitfield John B JB
INVESTIGATORS
JOURNAL
VOLUME: 11
ISSUE: 6
TITLE: Twin research and human genetics : the official journal of the International Society for Twin Studies
ISOABBREVIATION: Twin Res Hum Genet
YEAR: 2008
MONTH: Dec
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 1832-4274
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Twin Res Hum Genet
COUNTRY: England
ISSNLINKING: 1832-4274
NLMUNIQUEID: 101244624
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
AA007535 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adolescent Development
Australia
Cardiovascular Diseases genetics
Child genetics
Chromosomes, Human genetics
Female genetics
Follow-Up Studies genetics
Genome, Human genetics
Humans genetics
Lipid Metabolism genetics
Lipids genetics
Lod Score genetics
Male genetics
Retrospective Studies genetics
Twins, Dizygotic genetics
Twins, Monozygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Lipids
OTHER ID's