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.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
24340086
TITLE
Utilizing twins as controls for non-twin case-materials in genome wide association studies.
ABSTRACT
Twin registries around the globe have collected DNA samples from large numbers of monozygotic and dizygotic twins. The twin sample collections are frequently used as controls in disease-specific studies together with non-twins. This approach is unbiased under the hypothesis that twins and singletons are comparable in terms of allele frequencies; i.e. there are no genetic variants associated with being a twin per se. To test this hypothesis we performed a genome-wide association study comparing the allele frequency of 572,352 single nucleotide polymorphisms (SNPs) in 1,413 monozygotic (MZ) and 5,451 dizygotic (DZ) twins with 3,720 healthy singletons. Twins and singletons have been genotyped using the same platform. SNPs showing association with being a twin at P-value < 1 × 10(-5) were selected for replication analysis in 1,492 twins (463 MZ and 1,029 DZ) and 1,880 singletons from Finland. No SNPs reached genome-wide significance (P-value < 5 × 10(-8)) in the main analysis combining MZ and DZ twins. In a secondary analysis including only DZ twins two SNPs (rs2033541 close to ADAMTSL1 and rs4149283 close to ABCA1) were genome-wide significant after meta-analysis with the Finnish population. The estimated proportion of variance on the liability scale explained by all SNPs was 0.08 (P-value=0.003) when MZ and DZ were considered together and smaller for MZ (0.06, P-value=0.10) compared to DZ (0.09, P-value=0.003) when analyzed separately. In conclusion, twins and singletons can be used in genetic studies together with general population samples without introducing large bias. Further research is needed to explore genetic variances associated with DZ twinning.
DATE PUBLISHED
2013
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/07/03
accepted 2013/10/30
entrez 2013/12/17 06:00
pubmed 2013/12/18 06:00
medline 2014/10/01 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ganna A Ganna Andrea A Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ortega-Alonso A Ortega-Alonso Alfredo A
Havulinna A Havulinna Aki A
Salomaa V Salomaa Veikko V
Kaprio J Kaprio Jaakko J
Pedersen NL Pedersen Nancy L NL
Sullivan PF Sullivan Patrick F PF
Ingelsson E Ingelsson Erik E
Hultman CM Hultman Christina M CM
Magnusson PK Magnusson Patrik K E PK
INVESTIGATORS
JOURNAL
VOLUME: 8
ISSUE: 12
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2013
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
GRANTS
GRANTID AGENCY COUNTRY
K02AA018755 NIAAA NIH HHS United States
R01 MH077139 NIMH NIH HHS United States
DA12854 NIDA NIH HHS United States
AA-09203 NIAAA NIH HHS United States
AA-00145 NIAAA NIH HHS United States
AA15416 NIAAA NIH HHS United States
AA-12502 NIAAA NIH HHS United States
DK U01-066134 NIDDK NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Aged, 80 and over
Algorithms
Child
Female
Finland
Gene Frequency
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study methods
Genotype methods
Humans methods
Male methods
Middle Aged methods
Polymorphism, Single Nucleotide methods
Registries methods
Research Design methods
Sweden methods
Twins, Dizygotic genetics
Twins, Monozygotic genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's