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
18972745
TITLE
Use of monozygotic twins to investigate the relationship between 5HTTLPR genotype, depression and stressful life events: an application of Item Response Theory.
ABSTRACT
We examine the interaction between stressful life events (SLE) and genotypes for the length polymorphism of the serotonin receptor gene (5HTTLPR) on risk of depression. We hypothesize that if the interaction is real, monozygotic twin pairs (MZT) homozygous for the short allele (SS) will have a greater within pair variance in depression measures than MZT homozygous for the long allele (LL), as a reflection of their increased sensitivity to unknown environmental risk factors. Telephone interviews were used to assess symptoms of depression and suicidality on 824 MZT. Rather than using the interview items to calculate sum scores or allocate diagnostic classes we use Item Response Theory to model the contribution of each item to each individual's underlying liability to depression. SLE were also measured on the MZT assessed by mailed questionnaire on average 3.8 years previously, and these were used in follow-up analyses. We find no evidence for significant differences in within pair variance between 5HTTLPR genotypic classes and so can provide no support for interaction between these genotypes and the environment. The use of MZT provides a novel framework for examining genotype x environment interaction in the absence of measures on SLE.
DATE PUBLISHED
2008
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2008/11/01 09:00
medline 2008/12/17 09:00
entrez 2008/11/01 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Wray NR Wray Naomi R NR Genetic and Molecular Epidemiology Laboratories, Queensland Institute of Medical Research, Brisbane, 4006, Australia.
Coventry WL Coventry William L WL
James MR James Michael R MR
Montgomery GW Montgomery Grant W GW
Eaves LJ Eaves Lindon J LJ
Martin NG Martin Nicholas G NG
INVESTIGATORS
JOURNAL
VOLUME: 293
ISSUE:
TITLE: Novartis Foundation symposium
ISOABBREVIATION: Novartis Found. Symp.
YEAR: 2008
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 1528-2511
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Novartis Found Symp
COUNTRY: England
ISSNLINKING: 1528-2511
NLMUNIQUEID: 9807767
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
AA07535 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10249 NIAAA NIH HHS United States
MH068521 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Depression genetics
Female genetics
Genotype genetics
Humans genetics
Interview, Psychological genetics
Interviews as Topic genetics
Life Change Events genetics
Male genetics
Markov Chains genetics
Models, Genetic genetics
Models, Theoretical genetics
Polymorphism, Restriction Fragment Length genetics
Serotonin Plasma Membrane Transport Proteins genetics
Twins, Monozygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 SLC6A4 protein, human
0 Serotonin Plasma Membrane Transport Proteins
OTHER ID's