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
22530058
TITLE
Evidence of differential allelic effects between adolescents and adults for plasma high-density lipoprotein.
ABSTRACT
A recent meta-analysis of genome-wide association (GWA) studies identified 95 loci that influence lipid traits in the adult population and found that collectively these explained about 25-30% of heritability for each trait. Little is known about how these loci affect lipid levels in early life, but there is evidence that genetic effects on HDL- and LDL-cholesterol (HDL-C, LDL-C) and triglycerides vary with age. We studied Australian adults (N = 10,151) and adolescents (N = 2,363) who participated in twin and family studies and for whom we have lipid phenotypes and genotype information for 91 of the 95 genetic variants. Heterogeneity tests between effect sizes in adult and adolescent cohorts showed an excess of heterogeneity for HDL-C (p(Het)<0.05 at 5 out of 37 loci), but no more than expected by chance for LDL-C (1 out of 14 loci), or trigycerides (0 out 24). There were 2 (out of 5) with opposite direction of effect in adolescents compared to adults for HDL-C, but none for LDL-C. The biggest difference in effect size was for LDL-C at rs6511720 near LDLR, adolescents (0.021 ± 0.033 mmol/L) and adults (0.157 ± 0.023 mmol/L), p(Het) = 0.013; followed by ZNF664 (p(Het) = 0.018) and PABPC4 (p(Het) = 0.034) for HDL-C. Our findings suggest that some of the previously identified variants associate differently with lipid traits in adolescents compared to adults, either because of developmental changes or because of greater interactions with environmental differences in adults.
DATE PUBLISHED
2012
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/11/23
accepted 2012/03/22
epublish 2012/04/18
entrez 2012/04/25 06:00
pubmed 2012/04/25 06:00
medline 2012/12/10 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Middelberg RP Middelberg Rita P S RP Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia. ritaM@qimr.edu.au
Heath AC Heath Andrew C AC
Madden PA Madden Pamela A F PA
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Whitfield JB Whitfield John B JB
INVESTIGATORS
JOURNAL
VOLUME: 7
ISSUE: 4
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2012
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Twin Res. 2001 Feb;4(1):48-56 11665325
Cites Nat Genet. 2011 Jan;43(1):51-4 21151130
Cites Nat Genet. 2002 Jan;30(1):97-101 11731797
Cites Am J Epidemiol. 1981 Feb;113(2):157-70 7468573
Cites Biol Psychiatry. 2011 Sep 15;70(6):513-8 21529783
Cites Clin Chem. 1981 Aug;27(8):1469-70 7023754
Cites Atherosclerosis. 1983 Sep;48(3):265-77 6685521
Cites Behav Genet. 1985 Mar;15(2):93-109 3838073
Cites Clin Endocrinol (Oxf). 1991 Oct;35(4):305-10 1836425
Cites Am J Hum Genet. 1997 Mar;60(3):638-50 9042925
Cites Alcohol Clin Exp Res. 1998 Oct;22(7):1463-9 9802529
Cites Genet Epidemiol. 1999;16(1):40-53 9915566
Cites Twin Res. 1998 May;1(1):3-8 10051351
Cites Am J Hum Genet. 1999 Aug;65(2):483-92 10417291
Cites Twin Res Hum Genet. 2006 Aug;9(4):550-7 16899162
Cites Twin Res Hum Genet. 2007 Feb;10(1):127-35 17539372
Cites Nat Genet. 2009 Jan;41(1):56-65 19060906
Cites Nat Genet. 2009 Jan;41(1):47-55 19060911
Cites Mol Psychiatry. 2009 Apr;14(4):359-75 19065144
Cites Annu Rev Genomics Hum Genet. 2009;10:387-406 19715440
Cites Am J Hum Genet. 2009 Nov;85(5):750-5 19896111
Cites Nature. 2010 Aug 5;466(7307):707-13 20686565
Cites Bioinformatics. 2010 Sep 1;26(17):2190-1 20616382
Cites PLoS Genet. 2010 Sep;6(9):e1001094 20838585
Cites Genet Epidemiol. 2010 Dec;34(8):816-34 21058334
Cites Eur J Epidemiol. 2001;17(3):281-8 11680549
GRANTS
GRANTID AGENCY COUNTRY
84766/Z/08/Z Wellcome Trust United Kingdom
AA07535 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
AA17688 NIAAA NIH HHS United States
DA012854 NIDA NIH HHS United States
DA019951 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Alleles
Child
Cholesterol, HDL blood
Cholesterol, LDL blood
Female blood
Genetic Association Studies blood
Genotype blood
Humans blood
Hyperlipoproteinemias genetics
Male genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
Triglycerides blood
Young Adult blood
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Cholesterol, HDL
0 Cholesterol, LDL
0 Triglycerides
OTHER ID's
OTHERID SOURCE
PMC3329456 NLM