Dopaminergic gene polymorphisms and cognitive function in a north Indian schizophrenia cohort

Abstract

Background Associations of polymorphisms from dopaminergic neurotransmitter pathway genes have been reported in Caucasian ancestry schizophrenia (SZ) samples. As studies investigating single SNPs with SZ have been inconsistent, more detailed analyses utilizing multiple SNPs with the diagnostic phenotype as well as cognitive function may be more informative. The analyses were conducted in a north Indian sample. Methods Indian SZ case-parent trios (n = 601 families); unscreened controls (n= 468) and an independent set of 118 trio families were analyzed. Representative SNPs in the Dopamine D3 receptor (DRD3), dopamine transporter (SLC6A3), vesicular monoamine transporter 2 (SLC18A2), catechol-o-methyltransferase (COMT) and dopamine beta hydroxylase (DBH) were genotyped using SNaPshot/SNPlex assays (n=59 SNPs). The Trail Making Test (TMT) was administered to a subset of the sample (n=260 cases and_n=302 parents). Results Eight SNPs were nominally associated with SZ in either case-control or family based analyses (p<0.05, rs7631540 and rs2046496 in DRD3; rs363399 and rs10082463 in SLC18A2; rs4680, rs4646315 and rs9332377 in COMT). rs6271 at DBH was associated in both analyses. Haplotypes of DRD3 SNPs incorporating rs7631540-rs2134655-rs3773678-rs324030-rs6280-rs905568 showed suggestive associations in both case-parent and trio samples. At SLC18A2, rs10082463 was nominally associated with psychomotor performance and rs363285 with executive functions using the TMT but did not withstand multiple corrections. Conclusions Though suggestive associations with dopaminergic genes were detected in this study, but convincing links between dopaminergic polymorphisms and SZ or cognitive function were not observed.

Possible role of rare variants in Trace amine associated receptor 1 in schizophrenia

“…Patients with family history and receiving treatment for psychotic illnesses at Dr. RML Hospital, New Delhi were assessed using the Hindi version of the Diagnostic Interview for Genetic Studies (DIGS) and the Family Interview for Genetic Studies (FIGS) (Deshpande et al, 1998; Kukshal et al, 2013a, 2013b). Additional information was obtained from medical records and consensus diagnoses were assigned using DSM IV criteria.…”

“…Unaffected members from the multimembers affected family all of north Indian origin were also recruited alongside. In addition, ~1000 SZ cases and ~1050 ethnically matched controls of north Indian origin available in the laboratory and used in a few previous genetic association studies (John et al, 2016; Kukshal et al, 2013a, 2013b) were also included in the study. Further, ~310 sporadic SZ cases mostly of African-American/Caucasian origin (henceforth referred to as American samples) recruited at Western Psychiatric Institute and Clinic (WPIC), University of Pittsburgh School of Medicine, USA were used in this study.…”

Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin metabolism suggest association with cerebrospinal fluid monoamine metabolite concentrations in psychosis

“…Moreover, this SNP has been found to be associated with alcohol dependence in women [ 45 ]. Rs6271 was nominally associated with schizophrenia in both case–control and family based analyses in a north Indian schizophrenia cohort [ 46 ] and significantly associated with bipolar disorder in a Turkish population [ 47 ]. Rs1611118 and rs3025388 are intronic and to our knowledge, have not been ascribed any functionality or association with mental disorders.…”

Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder

“…Aripiprazole might also be used to treat PTSD. Polymorphisms in DRD3 are associated with Tourette (rs6280) [ 100 ], alcoholism [ 101 ] and schizophrenia [ 102 ].…”