Reshma Jabeen Taj M J1, Suhas Ganesh2, Tulika Shukla3, Sayali Deolankar4, Ravi K Nadella5, Somdatta Sen6, Meera Purushottam7, Y C Janardhan Reddy8, Sanjeev Jain9, Biju Viswanath10. 1. Molecular Genetics Laboratory, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: reshmataj7@gmail.com. 2. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: suhasg90@gmail.com. 3. Department of Psychiatry, Dr. Ram Manohar Lohia hospital, New Delhi, India. Electronic address: tulikawrite@gmail.com. 4. Molecular Genetics Laboratory, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: sayali.vit@gmail.com. 5. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: ravigmc2005@gmail.com. 6. Molecular Genetics Laboratory, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: sen.somdatta@gmail.com. 7. Molecular Genetics Laboratory, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: meera.purushottam@gmail.com. 8. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: ycjreddy@gmail.com. 9. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: sjain.nimhans@gmail.com. 10. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, India. Electronic address: bijuv1@gmail.com.
Abstract
AIM: Genetic etiology of Obsessive Compulsive Disorder (OCD) has been investigated extensively, with mixed results across candidate gene studies. The dimensional subtypes of OCD are shown to better correlate with brain imaging endophenotypes and thus could potentially enhance the power of genetic association. In this study, we perform a case control analysis of association of a single nucleotide polymorphism rs6265(Val66Met) in Brain Derived Neurotrophic Factor gene, that has been previously implicated in a variety of psychiatric syndromes, and examine its association with symptom dimensions of OCD. METHODS: Individuals diagnosed to have OCD (n=377) and controls (n=449) of South Indian origin were genotyped for polymorphism rs6265 (196G/A, Val66Met). Detailed phenotypic assessment of the cases were carried out in the cases using structured instruments. The genotypic association was tested for clinical variables such as age of onset, gender, family history, co-morbidity, treatment response, and factor analyzed OCD symptom dimensions. RESULTS: The allele 'A' frequency was found to be significantly higher in the controls, as compared to cases suggesting a protective effect. The contamination/washing symptom dimension score was significantly lower in carriers of 'A' allele which remained significant even after testing for confounding effects on linear regression. CONCLUSIONS: Our results support findings from previous studies on a possible protective effect of the 'Met' allele at the Val66Met locus in OCD. Its association with lower scores on the contamination/washing dimension is a novel finding of this study.
AIM: Genetic etiology of Obsessive Compulsive Disorder (OCD) has been investigated extensively, with mixed results across candidate gene studies. The dimensional subtypes of OCD are shown to better correlate with brain imaging endophenotypes and thus could potentially enhance the power of genetic association. In this study, we perform a case control analysis of association of a single nucleotide polymorphism rs6265(Val66Met) in Brain Derived Neurotrophic Factor gene, that has been previously implicated in a variety of psychiatric syndromes, and examine its association with symptom dimensions of OCD. METHODS: Individuals diagnosed to have OCD (n=377) and controls (n=449) of South Indian origin were genotyped for polymorphism rs6265 (196G/A, Val66Met). Detailed phenotypic assessment of the cases were carried out in the cases using structured instruments. The genotypic association was tested for clinical variables such as age of onset, gender, family history, co-morbidity, treatment response, and factor analyzed OCD symptom dimensions. RESULTS: The allele 'A' frequency was found to be significantly higher in the controls, as compared to cases suggesting a protective effect. The contamination/washing symptom dimension score was significantly lower in carriers of 'A' allele which remained significant even after testing for confounding effects on linear regression. CONCLUSIONS: Our results support findings from previous studies on a possible protective effect of the 'Met' allele at the Val66Met locus in OCD. Its association with lower scores on the contamination/washing dimension is a novel finding of this study.