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
19721450
TITLE
Multicenter dizygotic twin cohort study confirms two linkage susceptibility loci for body mass index at 3q29 and 7q36 and identifies three further potential novel loci.
ABSTRACT
OBJECTIVE NlmCategory: OBJECTIVE
To identify common loci and potential genetic variants affecting body mass index (BMI, kg m(-2)) in study populations originating from Europe.
DESIGN NlmCategory: METHODS
We combined genome-wide linkage scans of six cohorts from Australia, Denmark, Finland, the Netherlands, Sweden and the United Kingdom with an approximately 10-cM microsatellite marker map. Variance components linkage analysis was carried out with age, sex and country of origin as covariates.
SUBJECTS NlmCategory: METHODS
The GenomEUtwin consortium consists of twin cohorts from eight countries (Australia, Denmark, the Netherlands, Finland, Italy, Norway, Sweden and the United Kingdom) with a total data collection of more than 500,000 monozygotic and dizygotic (DZ) twin pairs. Variance due to early-life events and the environment is reduced within twin pairs, which makes DZ pairs highly valuable for linkage studies of complex traits. This study totaled 4401 European-originated twin families (10,535 individuals) from six countries (Australia, Denmark, the Netherlands, Finland, Sweden and the United Kingdom).
RESULTS NlmCategory: RESULTS
We found suggestive evidence for a quantitative trait locus on 3q29 and 7q36 in the combined sample of DZ twins (multipoint logarithm of odds score (MLOD) 2.6 and 2.4, respectively). Two individual cohorts showed strong evidence independently for three additional loci: 16q23 (MLOD=3.7) and 2p24 (MLOD=3.4) in the Dutch cohort and 20q13 (MLOD=3.2) in the Finnish cohort.
CONCLUSION NlmCategory: CONCLUSIONS
Linkage analysis of the combined data in this large twin cohort study provided evidence for suggestive linkage to BMI. In addition, two cohorts independently provided significant evidence of linkage to three new loci. The results of our study suggest a smaller environmental variance between DZ twins than full siblings, with a corresponding increase in heritability for BMI as well as an increase in linkage signal in well-replicated regions. The results are consistent with the possibility of locus heterogeneity for some genomic regions, and indicate a lack of major common quantitative trait locus variants affecting BMI in European populations.
DATE PUBLISHED
2009 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2009/09/01
entrez 2009/09/02 09:00
pubmed 2009/09/02 06:00
medline 2010/10/22 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Kettunen J Kettunen J J Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. johannes@sanger.ac.uk
Perola M Perola M M
Martin NG Martin N G NG
Cornes BK Cornes B K BK
Wilson SG Wilson S G SG
Montgomery GW Montgomery G W GW
Benyamin B Benyamin B B
Harris JR Harris J R JR
Boomsma D Boomsma D D
Willemsen G Willemsen G G
Hottenga JJ Hottenga J-J JJ
Slagboom PE Slagboom P E PE
Christensen K Christensen K K
Kyvik KO Kyvik K O KO
Sørensen TI Sørensen T I A TI
Pedersen NL Pedersen N L NL
Magnusson PK Magnusson P K E PK
Andrew T Andrew T T
Spector TD Spector T D TD
Widen E Widen E E
Silventoinen K Silventoinen K K
Kaprio J Kaprio J J
Palotie A Palotie A A
Peltonen L Peltonen L L
GenomEUtwin-project
INVESTIGATORS
JOURNAL
VOLUME: 33
ISSUE: 11
TITLE: International journal of obesity (2005)
ISOABBREVIATION: Int J Obes (Lond)
YEAR: 2009
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5497
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Int J Obes (Lond)
COUNTRY: England
ISSNLINKING: 0307-0565
NLMUNIQUEID: 101256108
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
072856 Wellcome Trust United Kingdom
089061 Wellcome Trust United Kingdom
1-R01-HL087679-01 NHLBI NIH HHS United States
AA007535 NIAAA NIH HHS United States
AA013320 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10249 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
R01 MH059160 NIMH NIH HHS United States
Biotechnology and Biological Sciences Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Body Mass Index
Chromosomes, Human, Pair 3 genetics
Chromosomes, Human, Pair 7 genetics
Cohort Studies genetics
Europe genetics
European Continental Ancestry Group genetics
Female genetics
Genetic Linkage genetics
Genetic Predisposition to Disease genetics
Humans genetics
Male genetics
Microsatellite Repeats genetics
Middle Aged genetics
Quantitative Trait Loci genetics
Twins genetics
Twins, Dizygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC2873558 NLM
UKMS30431 NLM
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