title: A quantitative association study between schizotypal traits and COMT, PRODH and BDNF genes in a healthy Chinese population.
abstract: Previous studies have suggested that catechol-O-methyltransferase (COMT), proline dehydrogenase (PRODH), and brain-derived neurotrophic factor (BDNF) genes are possible susceptibility genes for schizophrenia. We hypothesized that these genes are also associated with schizotypal traits, which are heritable and related to schizophrenia. We genotyped five single nucleotide polymorphism (SNPs) from the COMT, PRODH and BDNF genes, and performed a series of association analyses between alleles, genotypes or haplotypes, and quantitative schizotypal trait scores derived from the Schizotypal Personality Questionnaire (SPQ), in 465 Chinese healthy subjects. We found that 'years of education' was a major influence on seven out of nine schizotypal components, three schizotypal factors and the total SPQ scores. Molecular genetic analysis of COMT, PRODH and BDNF genes showed no significant effects of any variants on schizotypal components or factors of SPQ after correction for multiple testing, although there were weak association between COMT Val158Met (rs4680G/A) and the odd speech subscale (allele-wise, P=0.04; genotype-wise, P=0.049), between COMT Val158Met (rs4680G/A) and the suspiciousness subscale (genotype-wise, P=0.024), and between BDNF Val66Met and the Factor 2 interpersonal measure (genotype-wise, P=0.027) before correction. Furthermore, we found SNP Val158Met (rs4680) of the COMT gene significantly influenced the scores of some of schizotypal traits including total SPQ score, the disorganization factor and the constricted affect subscale in male subjects only. However, the effect was in the opposite direction of an earlier association with the SPQ reported by Avramopoulos et al. [Avramopoulos, D., Stefanis, N.C., Hantoumi, I., Smyrnis, N., Evdokimidis, I., Stefanis, C.N., 2002. Higher scores of self reported schizotypy in healthy young males carrying the COMT high activity allele. Molecular Psychiatry 7, 706-711]. We conclude that SNP Val158Met (rs4680) in the COMT gene may be associated with some schizotypal traits in male subjects, but our results are not conclusive.
authors.affiliation: Psychiatric Laboratory and Department of Psychiatry, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Ma
authors.forename: Jinhua
authors.initials: J
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Xueli
authors.initials: X
authors.lastname: Sun
authors.forename: Xiehe
authors.initials: X
authors.lastname: Liu
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000342:Affective Symptoms / Q000175:diagnosis / Q000235:genetics; D000367:Age Factors; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics* / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002681:China; D004522:Educational Status; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007398:Interpersonal Relations; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011394:Proline Oxidase / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics; D012564:Schizophrenic Language; D012569:Schizotypal Personality Disorder / Q000175:diagnosis / Q000235:genetics*; D012737:Sex Factors; D013223:Statistics as Topic
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011394:Proline Oxidase; D002394:Catechol O-Methyltransferase