|
|
| PMID |
|
|
| 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 |
|
|
| 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 |
|
|
|
