Systematic Reviews and Meta Analysis
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Meta-analysis of odds ratios for the COMT Gene rs737865 SNP for schizophrenia

Year 2024, Volume: 46 Issue: 4, 300 - 307, 31.12.2024

Gulden Hakverdi , Harika Gözükara Bağ

https://doi.org/10.7197/cmj.1606628

Abstract

ABSTRACT
Meta-analysis of COMT Gene rs737865 SNP odds ratios for schizophrenia
Background: The collection of methods that enable combining the findings of several independent studies on the topic of interest with appropriate statistical methods is called meta-analysis.
Schizophrenia is a complex psychiatric disease linked to many environmental and genetic factors and affects up to 1% of the world's population.
A candidate gene for schizophrenia susceptibility is the catechol-O-methyltransferase (COMT) gene.
This study aimed to combine the odds ratios obtained from different studies according to the rs737865 SNP (single nucleotide polymorphism) of the COMT gene for schizophrenia by meta-analysis.
Material and Method:
Publications written in English were scanned with the keywords "COMT and schizophrenia" in Web of Science, Pubmed, and Google Scholar databases until October 2024. Common odds ratio estimates were obtained with the help of appropriate meta-analytic methods under different genetic models for 17 studies that met the inclusion criteria, as well as 8 and 4 studies for Asians and Caucasians, respectively, by race. STATA 14 program was used for all analyses.
Results: Under different genetic models applied to seventeen studies, only carriers of the CC genotype were found to have a higher risk for schizophrenia than carriers of the T (TT+CT) allele [OR=1.133 (95% CI=1.008 - 1.273)]. In subgroup analyses according to race, no risk was found for Asians. In contrast, for Caucasians, it was found that carriers of the C (CC+CT) allele had an increased risk of schizophrenia compared to those with TT genotype [OR=1.586 (95% CI=1.349 - 1.865)].

Conclusion: With the help of applied meta-analytic methods, overall estimates were obtained for odds ratios (OR) obtained from independent studies under different genetic models. However, it is thought that the association between COMT gene rs737865 SNP and schizophrenia should be examined with studies conducted in larger groups homogeneous in terms of ethnicity.
Keywords: Meta-analysis, COMT, odds ratio, schizophrenia.

Keywords

Meta-analysis COMT odds ratio schizophrenia.

Ethical Statement

Meta analiz çalışması olup etk kurul gerekmemektedir.

Project Number

BAP 2016/149

References

  • 1. Wilson DB, Lipsey MW. The role of method in treatment effectiveness research: Evidence from meta-analysis. Psychological Methods. 2001;6(4):413-429. doi:https://doi.org/10.1037/1082-989x.6.4.413
  • 2. Schulze R. The State and the Art of Meta-Analysis. Zeitschrift für Psychologie / Journal of Psychology. 2007;215(2):87-89. doi:https://doi.org/10.1027/0044-3409.215.2.87
  • 3. Rothman KJ, Sander Greenland, Lash TL. Modern Epidemiology. Wolters Kluwer Health/Lippincott Williams & Wilkins; 2008.
  • 4. Shifman S, Bronstein M, Sternfeld M, et al. A Highly Significant Association between a COMT Haplotype and Schizophrenia. The American Journal of Human Genetics. 2002;71(6):1296-1302. doi:https://doi.org/10.1086/344514
  • 5. Nunokawa A, Watanabe Y, Tatsuyuki Muratake, Kaneko N, Koizumi M, Toshiyuki Someya. No associations exist between five functional polymorphisms in the catechol-O-methyltransferase gene and schizophrenia in a Japanese population. Neuroscience Research. 2007;58(3):291-296. doi:https://doi.org/10.1016/j.neures.2007.03.015
  • 6. Galen E.B. Wright, Dana J.H. Niehaus, van, et al. Association of MB-COMT polymorphisms with schizophrenia-susceptibility and symptom severity in an African cohort. Progress in Neuro-psychopharmacology & Biological Psychiatry. 2012;39(1):163-169. doi:https://doi.org/10.1016/j.pnpbp.2012.06.006
  • 7. Martorell L, Costas J, Valero J, et al. Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia. Schizophrenia Research. 2008;100(1-3):308-315. doi:https://doi.org/10.1016/j.schres.2007.11.001
  • 8. Lee SG, Yeon Ho Joo, Kim BS, et al. Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans. Hum Genet. 2005;116(4):319-328. doi:https://doi.org/10.1007/s00439-004-1239-y
  • 9. Funke B, Malhotra AK, Finn CT, et al. COMT genetic variation confers risk for psychotic and affective disorders: a case control study. Behavioral and brain functions: BBF. 2005;18:1-19. doi: https://doi.org/10.1186/1744-9081-1-19
  • 10. Chen CY ., Lu RB ., Yeh YW ., Shih MC ., Huang SY . Association study of catechol-O-methyltransferase gene polymorphisms with schizophrenia and psychopathological symptoms in Han Chinese. Genes, Brain and Behavior. 2011;10(3):316-324. doi:https://doi.org/10.1111/j.1601-183x.2010.00670.x
  • 11. Higashiyama R, Ohnuma T, Takebayashi Y, et al. Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2016;171(3):447-457. doi:https://doi.org/10.1002/ajmg.b.32426
  • 12. Yu R, Zhang X, Huang X, Ding S, Li J. Association analysis of COMT polymorphisms and schizophrenia in a Chinese Han population: A case‐control study. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2007;144B(4):570-573. doi:https://doi.org/10.1002/ajmg.b.30487
  • 13. Maria K, Charalampos T, Vassilakopoulou D, Stavroula S, Vasiliki K, Nikolaos D. Frequency Distribution of COMT Polymorphisms in Greek Patients with Schizophrenia and Controls: A Study of SNPs rs737865, rs4680, and rs165599. ISRN Psychiatry. 2012;2012:1-6. doi:https://doi.org/10.5402/2012/651613
  • 14. Acar C, Sözen MM, Gözükara H, Orman K, Kartalcı Ş. Lack of association between catechol-Omethyltransferase and schizophrenia in a Turkish population. Turkish Journal of Biochemistry. 2015;40(3). doi:https://doi.org/10.1515/tjb-2015-0002
  • 15. Talkowski ME, Kirov G, Bamne M, et al. A network of dopaminergic gene variations implicated as risk factors for schizophrenia. Human Molecular Genetics. 2007;17(5):747-758. doi:https://doi.org/10.1093/hmg/ddm347
  • 16. Okochi T, Ikeda M, Kishi T, et al. Meta-analysis of association between genetic variants in COMT and schizophrenia: An update. Schizophrenia Research. 2009;110(1-3):140-148. doi:https://doi.org/10.1016/j.schres.2009.02.019
  • 17. Dean B, Scarr E. COMT genotype is associated with differential expression of muscarinic M1 receptors in human cortex. American journal of medical genetics Part B, Neuropsychiatric genetics. 2016;171(6):784-789. doi:https://doi.org/10.1002/ajmg.b.32440
  • 18. Chien YL, Liu CM, Fann CSJ, Liu YL, Hwu HG. Association of the 3′ Region of COMT with Schizophrenia in Taiwan. Journal of the Formosan Medical Association. 2009;108(4):301-309. doi:https://doi.org/10.1016/s0929-6646(09)60070-x
  • 19. Park BL, Shin HD, Cheong HS, et al. Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality. Journal of Human Genetics. 2009;54(12):709-712. doi:https://doi.org/10.1038/jhg.2009.102
  • 20. Gupta M, Bhatnagar P, Grover S, et al. Association studies of catechol-O-methyltransferase (COMT) gene with schizophrenia and response to antipsychotic treatment. Pharmacogenomics. 2009;10(3):385-397. doi:https://doi.org/10.2217/14622416.10.3.385
  • 21. Handoko HY, Nyholt DR, Hayward NK, et al. Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia. Molecular Psychiatry. 2004;10(6):589-597. doi:https://doi.org/10.1038/sj.mp.4001606
  • 22. Salisbury BA, Pungliya M, Choi JY, Jiang R, Sun XJ, Stephens JClaiborne. SNP and haplotype variation in the human genome. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2003;526(1-2):53-61. doi:https://doi.org/10.1016/s0027-5107(03)00014-9
  • 23. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Systematic Reviews. 2021;10(1). https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-021-01626-4
  • 24. Matsuzaka CT, Christofolini D, Ota VK, et al. Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls. Brazilian Journal of Psychiatry. 2017;39(4):302-308. doi:https://doi.org/10.1590/1516-4446-2016-1987
  • 25. Agresti A. Categorical Data Analysis. John Wiley & Sons; 2013.
  • 26. Alpar R. Uygulamalı Çok Değişkenli Istatistiksel Yöntemler. 3rd ed. Detay Yayıncılık; 2013.
  • 27. Gozukara Bag HG. Association between COMT gene rs165599 SNP and schizophrenia: A meta-analysis of case-control studies. Molecular Genetics & Genomic Medicine. 2018;6(5):845-854. doi:https://doi.org/10.1002/mgg3.468
  • 28. Lau J, Ioannidis JP, Schmid C. Quantitative Synthesis in Systematic Reviews. Annals of Internal Medicine. 1997;127(9):820. doi:https://doi.org/10.7326/0003-4819-127-9-199711010-00008
  • 29. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-560. doi:https://doi.org/10.1136/bmj.327.7414.557
  • 30. Mukherjee N, Kidd KK, Pakstis AJ, et al. The complex global pattern of genetic variation and linkage disequilibrium at catechol- O -methyltransferase. Molecular Psychiatry. 2010;15(2):216-225. doi:https://doi.org/10.1038/mp.2008.64

Şizofreni için COMT Geni rs737865 SNP odds oranlarının meta analizi

Year 2024, Volume: 46 Issue: 4, 300 - 307, 31.12.2024

Gulden Hakverdi , Harika Gözükara Bağ

https://doi.org/10.7197/cmj.1606628

Abstract

Özet
Amaç: İlgilenilen konuda yapılan birden çok bağımsız çalışmanın bulgularını uygun istatistiksel metotlarla birleştirmeyi sağlayan metotlar topluluğuna meta analizi adı verilir.
Şizofreni, birçok çevresel ve genetik faktörle bağlantılı karmaşık bir psikiyatrik hastalıktır ve dünya nüfusunun %1'ini etkilemektedir. Katekol-O-Metiltransferaz (COMT) geni şizofreniye yatkınlık için aday bir gen olarak görülmektedir. Bu çalışmada, şizofreni için COMT geninin rs737865 SNP’ne (tek nükleotit polimorfizmi) göre farklı çalışmalardan elde edilen odds oranlarının meta analizi ile birleştirilmesi amaçlanmıştır.
Materyal ve Metot: Yazım dili İngilizce olan yayınlar "COMT ve şizofreni" anahtar kelimeleri ile Ekim 2024 tarihine kadar Web of Science, Pubmed ve Google Akademik veri tabanlarında ile taranmıştır. Dâhil olma kriterlerini sağlayan 17 çalışma ve ayrıca ırka göre Asyalı ve Beyaz ırklar için sırasıyla 8 ve 4 çalışma için farklı genetik modeller altında, uygun meta analitik yöntemler yardımıyla ortak odds oranı kestirimleri elde edillmiştir. Tüm analizlerde STATA 14.0 programı kullanılmıştır.
Bulgular: On yedi çalışmaya uygulanan farklı genetik modeller altında, sadece CC genotipine sahip olanların T (TT+CT) alleli taşıyıcılarına göre şizofreni için risk taşıdığı bulunmuştur [OR=1,133 (%95 G.A.=1,008 – 1,273)]. Irka göre yapılan alt grup analizlerinde ise Asyalı ırk için bir riskten söz edemezken Beyaz ırk için C (CC+CT) alleli taşıyıcılarının TT genotipine sahip olanlara göre şizofreni riskini arttırdığı bulunmuştur [OR=1,586 (%95 G.A.=1,349 – 1,865)].
Sonuç: Uygulanan meta-analitik yöntemler yardımıyla bağımsız çalışmalardan elde edilen odds oranları (OR) için farklı genetik modeller altında tümel kestirimler elde edilmiştir. Bununla birlikte, etnik köken açısından homojen daha büyük gruplarda yapılan çalışmalar ile COMT geni rs737865 SNP’i ile şizofreni arasındaki bağın incelenmesi gerektiği düşünülmektedir.

Keywords

Meta analiz COMT odds oranı şizofreni.

Ethical Statement

Yüksek lisans tezimin makalesi olup, meta analiz çalışması olduğundan ve açık erişimli çalışmalar dahil edildiğinden dolayı etik kurul belgesi gerekmemektedir.

Supporting Institution

İnönü Üniversitesi Bilimsel Araştırma Projeleri (BAP) birimi

Project Number

BAP 2016/149

Thanks

İnönü Üniversitesi Bilimsel Araştırma Projeleri (BAP) birimi

References

  • 1. Wilson DB, Lipsey MW. The role of method in treatment effectiveness research: Evidence from meta-analysis. Psychological Methods. 2001;6(4):413-429. doi:https://doi.org/10.1037/1082-989x.6.4.413
  • 2. Schulze R. The State and the Art of Meta-Analysis. Zeitschrift für Psychologie / Journal of Psychology. 2007;215(2):87-89. doi:https://doi.org/10.1027/0044-3409.215.2.87
  • 3. Rothman KJ, Sander Greenland, Lash TL. Modern Epidemiology. Wolters Kluwer Health/Lippincott Williams & Wilkins; 2008.
  • 4. Shifman S, Bronstein M, Sternfeld M, et al. A Highly Significant Association between a COMT Haplotype and Schizophrenia. The American Journal of Human Genetics. 2002;71(6):1296-1302. doi:https://doi.org/10.1086/344514
  • 5. Nunokawa A, Watanabe Y, Tatsuyuki Muratake, Kaneko N, Koizumi M, Toshiyuki Someya. No associations exist between five functional polymorphisms in the catechol-O-methyltransferase gene and schizophrenia in a Japanese population. Neuroscience Research. 2007;58(3):291-296. doi:https://doi.org/10.1016/j.neures.2007.03.015
  • 6. Galen E.B. Wright, Dana J.H. Niehaus, van, et al. Association of MB-COMT polymorphisms with schizophrenia-susceptibility and symptom severity in an African cohort. Progress in Neuro-psychopharmacology & Biological Psychiatry. 2012;39(1):163-169. doi:https://doi.org/10.1016/j.pnpbp.2012.06.006
  • 7. Martorell L, Costas J, Valero J, et al. Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia. Schizophrenia Research. 2008;100(1-3):308-315. doi:https://doi.org/10.1016/j.schres.2007.11.001
  • 8. Lee SG, Yeon Ho Joo, Kim BS, et al. Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans. Hum Genet. 2005;116(4):319-328. doi:https://doi.org/10.1007/s00439-004-1239-y
  • 9. Funke B, Malhotra AK, Finn CT, et al. COMT genetic variation confers risk for psychotic and affective disorders: a case control study. Behavioral and brain functions: BBF. 2005;18:1-19. doi: https://doi.org/10.1186/1744-9081-1-19
  • 10. Chen CY ., Lu RB ., Yeh YW ., Shih MC ., Huang SY . Association study of catechol-O-methyltransferase gene polymorphisms with schizophrenia and psychopathological symptoms in Han Chinese. Genes, Brain and Behavior. 2011;10(3):316-324. doi:https://doi.org/10.1111/j.1601-183x.2010.00670.x
  • 11. Higashiyama R, Ohnuma T, Takebayashi Y, et al. Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2016;171(3):447-457. doi:https://doi.org/10.1002/ajmg.b.32426
  • 12. Yu R, Zhang X, Huang X, Ding S, Li J. Association analysis of COMT polymorphisms and schizophrenia in a Chinese Han population: A case‐control study. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2007;144B(4):570-573. doi:https://doi.org/10.1002/ajmg.b.30487
  • 13. Maria K, Charalampos T, Vassilakopoulou D, Stavroula S, Vasiliki K, Nikolaos D. Frequency Distribution of COMT Polymorphisms in Greek Patients with Schizophrenia and Controls: A Study of SNPs rs737865, rs4680, and rs165599. ISRN Psychiatry. 2012;2012:1-6. doi:https://doi.org/10.5402/2012/651613
  • 14. Acar C, Sözen MM, Gözükara H, Orman K, Kartalcı Ş. Lack of association between catechol-Omethyltransferase and schizophrenia in a Turkish population. Turkish Journal of Biochemistry. 2015;40(3). doi:https://doi.org/10.1515/tjb-2015-0002
  • 15. Talkowski ME, Kirov G, Bamne M, et al. A network of dopaminergic gene variations implicated as risk factors for schizophrenia. Human Molecular Genetics. 2007;17(5):747-758. doi:https://doi.org/10.1093/hmg/ddm347
  • 16. Okochi T, Ikeda M, Kishi T, et al. Meta-analysis of association between genetic variants in COMT and schizophrenia: An update. Schizophrenia Research. 2009;110(1-3):140-148. doi:https://doi.org/10.1016/j.schres.2009.02.019
  • 17. Dean B, Scarr E. COMT genotype is associated with differential expression of muscarinic M1 receptors in human cortex. American journal of medical genetics Part B, Neuropsychiatric genetics. 2016;171(6):784-789. doi:https://doi.org/10.1002/ajmg.b.32440
  • 18. Chien YL, Liu CM, Fann CSJ, Liu YL, Hwu HG. Association of the 3′ Region of COMT with Schizophrenia in Taiwan. Journal of the Formosan Medical Association. 2009;108(4):301-309. doi:https://doi.org/10.1016/s0929-6646(09)60070-x
  • 19. Park BL, Shin HD, Cheong HS, et al. Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality. Journal of Human Genetics. 2009;54(12):709-712. doi:https://doi.org/10.1038/jhg.2009.102
  • 20. Gupta M, Bhatnagar P, Grover S, et al. Association studies of catechol-O-methyltransferase (COMT) gene with schizophrenia and response to antipsychotic treatment. Pharmacogenomics. 2009;10(3):385-397. doi:https://doi.org/10.2217/14622416.10.3.385
  • 21. Handoko HY, Nyholt DR, Hayward NK, et al. Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia. Molecular Psychiatry. 2004;10(6):589-597. doi:https://doi.org/10.1038/sj.mp.4001606
  • 22. Salisbury BA, Pungliya M, Choi JY, Jiang R, Sun XJ, Stephens JClaiborne. SNP and haplotype variation in the human genome. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2003;526(1-2):53-61. doi:https://doi.org/10.1016/s0027-5107(03)00014-9
  • 23. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Systematic Reviews. 2021;10(1). https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-021-01626-4
  • 24. Matsuzaka CT, Christofolini D, Ota VK, et al. Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls. Brazilian Journal of Psychiatry. 2017;39(4):302-308. doi:https://doi.org/10.1590/1516-4446-2016-1987
  • 25. Agresti A. Categorical Data Analysis. John Wiley & Sons; 2013.
  • 26. Alpar R. Uygulamalı Çok Değişkenli Istatistiksel Yöntemler. 3rd ed. Detay Yayıncılık; 2013.
  • 27. Gozukara Bag HG. Association between COMT gene rs165599 SNP and schizophrenia: A meta-analysis of case-control studies. Molecular Genetics & Genomic Medicine. 2018;6(5):845-854. doi:https://doi.org/10.1002/mgg3.468
  • 28. Lau J, Ioannidis JP, Schmid C. Quantitative Synthesis in Systematic Reviews. Annals of Internal Medicine. 1997;127(9):820. doi:https://doi.org/10.7326/0003-4819-127-9-199711010-00008
  • 29. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-560. doi:https://doi.org/10.1136/bmj.327.7414.557
  • 30. Mukherjee N, Kidd KK, Pakstis AJ, et al. The complex global pattern of genetic variation and linkage disequilibrium at catechol- O -methyltransferase. Molecular Psychiatry. 2010;15(2):216-225. doi:https://doi.org/10.1038/mp.2008.64
There are 30 citations in total.

Details

Primary Language English
Subjects Health Informatics and Information Systems, Implementation Science and Evaluation
Journal Section Meta-analysis and Systematic Review
Authors

Gulden Hakverdi 0000-0002-8078-0451

Harika Gözükara Bağ 0000-0003-1208-4072

Project Number BAP 2016/149
Publication Date December 31, 2024
Submission Date December 24, 2024
Acceptance Date December 28, 2024
Published in Issue Year 2024Volume: 46 Issue: 4

Cite

AMA Hakverdi G, Gözükara Bağ H. Meta-analysis of odds ratios for the COMT Gene rs737865 SNP for schizophrenia. CMJ. December 2024;46(4):300-307. doi:10.7197/cmj.1606628
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