Association of SLC6A4 variants with obsessive-compulsive disorder in a large multicenter US family study.
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| Title: | Association of SLC6A4 variants with obsessive-compulsive disorder in a large multicenter US family study. |
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| Authors: | Voyiaziakis, E., Evgrafov, O., D. Li, H-J Yoon, Tabares, P., Samuels, J., Y. Wang, Riddle, M. A., Grados, M. A., Bienvenu, O. J., Shugart, Y. Y., K-Y Liang, Greenberg, B. D., Rasmussen, S. A., Murphy, D. L., Wendland, J. R., McCracken, J. T., Piacentini, J., Rauch, S. L., Pauls, D. L. |
| Source: | Molecular Psychiatry. Jan2011, Vol. 16 Issue 1, p108-120. 13p. 5 Charts. |
| Subjects: | Genetic research, Obsessive-compulsive disorder, Genetic polymorphisms, Linkage (Genetics), Phenotypes |
| Abstract: | Genetic association studies of SLC6A4 (SERT) and obsessive-compulsive disorder (OCD) have been equivocal. We genotyped 1241 individuals in 278 pedigrees from the OCD Collaborative Genetics Study for 13 single-nucleotide polymorphisms, for the linked polymorphic region (LPR) indel with molecular haplotypes at rs25531, for VNTR polymorphisms in introns 2 and 7 and for a 381-bp deletion 3′ to the LPR. We analyzed using the Family-Based Association Test (FBAT) under additive, dominant, recessive and genotypic models, using both OCD and sex-stratified OCD as phenotypes. Two-point FBAT analysis detected association between Int2 (P=0.0089) and Int7 (P=0.0187) (genotypic model). Sex-stratified two-point analysis showed strong association in females with Int2 (P<0.0002), significant after correction for linkage disequilibrium, and multiple marker and model testing (PAdj=0.0069). The SLC6A4 gene is composed of two haplotype blocks (our data and the HapMap); FBAT whole-marker analysis conducted using this structure was not significant. Several noteworthy nonsignificant results have emerged. Unlike Hu et al., we found no evidence for overtransmission of the LPR LA allele (genotype relative risk=1.11, 95% confidence interval: 0.77-1.60); however, rare individual haplotypes containing LA with P<0.05 were observed. Similarly, three individuals (two with OCD/OCPD) carried the rare I425V SLC6A4 variant, but none of them passed it on to their six OCD-affected offspring, suggesting that it is unlikely to be solely responsible for the 'OCD plus syndrome', as reported by Ozaki et al. In conclusion, we found evidence of genetic association at the SLC6A4 locus with OCD. A noteworthy lack of association at the LPR, LPR-rs25531 and rare 425V variants suggests that hypotheses about OCD risk need revision to accommodate these new findings, including a possible gender effect. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 56512328 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Association of SLC6A4 variants with obsessive-compulsive disorder in a large multicenter US family study. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Voyiaziakis%2C+E%2E%22">Voyiaziakis, E.</searchLink><br /><searchLink fieldCode="AR" term="%22Evgrafov%2C+O%2E%22">Evgrafov, O.</searchLink><br /><searchLink fieldCode="AR" term="%22D%2E+Li%22">D. Li</searchLink><br /><searchLink fieldCode="AR" term="%22H-J+Yoon%22">H-J Yoon</searchLink><br /><searchLink fieldCode="AR" term="%22Tabares%2C+P%2E%22">Tabares, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Samuels%2C+J%2E%22">Samuels, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Y%2E+Wang%22">Y. Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Riddle%2C+M%2E+A%2E%22">Riddle, M. A.</searchLink><br /><searchLink fieldCode="AR" term="%22Grados%2C+M%2E+A%2E%22">Grados, M. A.</searchLink><br /><searchLink fieldCode="AR" term="%22Bienvenu%2C+O%2E+J%2E%22">Bienvenu, O. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Shugart%2C+Y%2E+Y%2E%22">Shugart, Y. Y.</searchLink><br /><searchLink fieldCode="AR" term="%22K-Y+Liang%22">K-Y Liang</searchLink><br /><searchLink fieldCode="AR" term="%22Greenberg%2C+B%2E+D%2E%22">Greenberg, B. D.</searchLink><br /><searchLink fieldCode="AR" term="%22Rasmussen%2C+S%2E+A%2E%22">Rasmussen, S. A.</searchLink><br /><searchLink fieldCode="AR" term="%22Murphy%2C+D%2E+L%2E%22">Murphy, D. L.</searchLink><br /><searchLink fieldCode="AR" term="%22Wendland%2C+J%2E+R%2E%22">Wendland, J. R.</searchLink><br /><searchLink fieldCode="AR" term="%22McCracken%2C+J%2E+T%2E%22">McCracken, J. T.</searchLink><br /><searchLink fieldCode="AR" term="%22Piacentini%2C+J%2E%22">Piacentini, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Rauch%2C+S%2E+L%2E%22">Rauch, S. L.</searchLink><br /><searchLink fieldCode="AR" term="%22Pauls%2C+D%2E+L%2E%22">Pauls, D. L.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Jan2011, Vol. 16 Issue 1, p108-120. 13p. 5 Charts. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Genetic+research%22">Genetic research</searchLink><br /><searchLink fieldCode="DE" term="%22Obsessive-compulsive+disorder%22">Obsessive-compulsive disorder</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Linkage+%28Genetics%29%22">Linkage (Genetics)</searchLink><br /><searchLink fieldCode="DE" term="%22Phenotypes%22">Phenotypes</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Genetic association studies of SLC6A4 (SERT) and obsessive-compulsive disorder (OCD) have been equivocal. We genotyped 1241 individuals in 278 pedigrees from the OCD Collaborative Genetics Study for 13 single-nucleotide polymorphisms, for the linked polymorphic region (LPR) indel with molecular haplotypes at rs25531, for VNTR polymorphisms in introns 2 and 7 and for a 381-bp deletion 3′ to the LPR. We analyzed using the Family-Based Association Test (FBAT) under additive, dominant, recessive and genotypic models, using both OCD and sex-stratified OCD as phenotypes. Two-point FBAT analysis detected association between Int2 (P=0.0089) and Int7 (P=0.0187) (genotypic model). Sex-stratified two-point analysis showed strong association in females with Int2 (P<0.0002), significant after correction for linkage disequilibrium, and multiple marker and model testing (PAdj=0.0069). The SLC6A4 gene is composed of two haplotype blocks (our data and the HapMap); FBAT whole-marker analysis conducted using this structure was not significant. Several noteworthy nonsignificant results have emerged. Unlike Hu et al., we found no evidence for overtransmission of the LPR LA allele (genotype relative risk=1.11, 95% confidence interval: 0.77-1.60); however, rare individual haplotypes containing LA with P<0.05 were observed. Similarly, three individuals (two with OCD/OCPD) carried the rare I425V SLC6A4 variant, but none of them passed it on to their six OCD-affected offspring, suggesting that it is unlikely to be solely responsible for the 'OCD plus syndrome', as reported by Ozaki et al. In conclusion, we found evidence of genetic association at the SLC6A4 locus with OCD. A noteworthy lack of association at the LPR, LPR-rs25531 and rare 425V variants suggests that hypotheses about OCD risk need revision to accommodate these new findings, including a possible gender effect. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/mp.2009.100 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 108 Subjects: – SubjectFull: Genetic research Type: general – SubjectFull: Obsessive-compulsive disorder Type: general – SubjectFull: Genetic polymorphisms Type: general – SubjectFull: Linkage (Genetics) Type: general – SubjectFull: Phenotypes Type: general Titles: – TitleFull: Association of SLC6A4 variants with obsessive-compulsive disorder in a large multicenter US family study. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Voyiaziakis, E. – PersonEntity: Name: NameFull: Evgrafov, O. – PersonEntity: Name: NameFull: D. Li – PersonEntity: Name: NameFull: H-J Yoon – PersonEntity: Name: NameFull: Tabares, P. – PersonEntity: Name: NameFull: Samuels, J. – PersonEntity: Name: NameFull: Y. Wang – PersonEntity: Name: NameFull: Riddle, M. A. – PersonEntity: Name: NameFull: Grados, M. A. – PersonEntity: Name: NameFull: Bienvenu, O. J. – PersonEntity: Name: NameFull: Shugart, Y. Y. – PersonEntity: Name: NameFull: K-Y Liang – PersonEntity: Name: NameFull: Greenberg, B. D. – PersonEntity: Name: NameFull: Rasmussen, S. A. – PersonEntity: Name: NameFull: Murphy, D. L. – PersonEntity: Name: NameFull: Wendland, J. R. – PersonEntity: Name: NameFull: McCracken, J. T. – PersonEntity: Name: NameFull: Piacentini, J. – PersonEntity: Name: NameFull: Rauch, S. L. – PersonEntity: Name: NameFull: Pauls, D. L. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 01 Text: Jan2011 Type: published Y: 2011 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 16 – Type: issue Value: 1 Titles: – TitleFull: Molecular Psychiatry Type: main |
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