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Utilizing twins as controls for non-twin case-materials in genome wide association studies.
PLoS One. 2013; 8(12):e83101.Plos

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.

Authors+Show Affiliations

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24340086

Citation

Ganna, Andrea, et al. "Utilizing Twins as Controls for Non-twin Case-materials in Genome Wide Association Studies." PloS One, vol. 8, no. 12, 2013, pp. e83101.
Ganna A, Ortega-Alonso A, Havulinna A, et al. Utilizing twins as controls for non-twin case-materials in genome wide association studies. PLoS ONE. 2013;8(12):e83101.
Ganna, A., Ortega-Alonso, A., Havulinna, A., Salomaa, V., Kaprio, J., Pedersen, N. L., Sullivan, P. F., Ingelsson, E., Hultman, C. M., & Magnusson, P. K. (2013). Utilizing twins as controls for non-twin case-materials in genome wide association studies. PloS One, 8(12), e83101. https://doi.org/10.1371/journal.pone.0083101
Ganna A, et al. Utilizing Twins as Controls for Non-twin Case-materials in Genome Wide Association Studies. PLoS ONE. 2013;8(12):e83101. PubMed PMID: 24340086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Utilizing twins as controls for non-twin case-materials in genome wide association studies. AU - Ganna,Andrea, AU - Ortega-Alonso,Alfredo, AU - Havulinna,Aki, AU - Salomaa,Veikko, AU - Kaprio,Jaakko, AU - Pedersen,Nancy L, AU - Sullivan,Patrick F, AU - Ingelsson,Erik, AU - Hultman,Christina M, AU - Magnusson,Patrik K E, Y1 - 2013/12/10/ PY - 2013/07/03/received PY - 2013/10/30/accepted PY - 2013/12/17/entrez PY - 2013/12/18/pubmed PY - 2014/10/1/medline SP - e83101 EP - e83101 JF - PloS one JO - PLoS ONE VL - 8 IS - 12 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24340086/Utilizing_twins_as_controls_for_non_twin_case_materials_in_genome_wide_association_studies_ L2 - http://dx.plos.org/10.1371/journal.pone.0083101 DB - PRIME DP - Unbound Medicine ER -