Identifying novel risk conferring genes involved in glycosylation processes with familial schizophrenia in an Indian cohort: Prediction of ADAMTS9 gene variant for structural stability.

Schizophrenia is a complex neuropsychiatric disorder and heritability is as high as 80 % making it the most heritable mental disorder. Although GWAS has identified numerous variants, the pathophysiology is still elusive. Here, an attempt was made to identify genetic risk factors in familial cases of schizophrenia that are associated with a common causative pathway. To achieve this objective, exome sequencing was done in 4 familial cases and identified six unique coding variants in five genes. Among these genes, PIGQ gene has two pathogenic variants, one nonsense and in-frame deletion. One missense variant in GALNT16 and one in GALNT5 have variable damaging score, however, the other variants, in ADAMTS9 and in LTBP4 have the highest damaging score. Further analysis showed that the variant of LTBP4 was not present in the functional domain. The other missense variant in the ADAMTS9 gene was found to be significant and was present in the thrombospondin repeat motif, one of the important motifs. Detailed molecular dynamics simulation study on this variant showed a damaging effect on structural stability. Since, all these genes culminated into the glycosylation process, it was evident that an aberrant glycosylation process may be one of the risk factors. Although, extracellular matrix formation through glycosylation have been shown to be associated, the involvement of ADAMTS9 and PIGQ gene mediated glycosylation has not been reported. In this paper, a novel link between ADAMTS9 and PIGQ gene with schizophrenia have been reported. Therefore, this novel observation has contributed immensely to the existing knowledge on risk factor of Schizophrenia.

Assessment of sleep quality in post-graduate residents in a tertiary hospital and teaching institute.

OBJECTIVES: To evaluate subjective sleep quality, day-time sleepiness, prevalence of substance use, satisfaction with life among residents at our institute. To evaluate association of sleep qualitywith satisfaction with life and day-time sleepiness. To compare the findings between residents in clinical and para-clinical departments. MATERIALS AND METHODS: Eighty-four residents filled questionnaires to obtain socio-demographic information and use of substance (s). Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Satisfaction With Life scale (SWLS) were also used. Association between sleep quality and sleepiness and satisfaction with life was evaluated. From the data collected, comparisons were made between the clinical and para-clinical department residents. RESULTS: A significant number of residents belonging to the clinical faculty were poorsleepers; reported high levels of abnormal day-time sleepiness and less satisfaction with life compared to residents in para-clinical faculties. The differences in correlation between sleepiness and satisfaction with life with sleep quality among the two groups were not found to be significant. A larger percentage of clinical residents reported use of at least one substance during the residency period compared to the para-clinical residents. CONCLUSIONS: Poor sleep quality is perceived greatly by the resident doctors in our public hospital, especially among clinical faculties. Interventions are thus necessary in order to ensure adequate sleep among them.