Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Association of common and rare genetic variants with cognition in schizophrenia

Cognitive dysfunction is one of the core features in schizophrenia (SZ), which is a common neuro-psychiatric disorder affecting ~1% of the population globally. Cognitive impairment is related to social deficits with severity and breadth of these impairments varying across patients. Further, different cognitive domains seem to be dysfunctional in different patients. Severity of cognitive decline depends on the age of onset of SZ, with higher severity in early onset cases and generally manifests before the actual onset of psychosis. Though estimated heritability of cognition is ~50-70% little is known about its genetic basis. Of note, contemporary antipsychotic medication is also not effective in addressing this endophenotype. In this study we recruited SZ patients (n=158) from Dr. RML hospital, New Delhi and assessment of cognition was performed using Hindi version of University of Pennsylvania Computerized Neurocognitive Battery (Penn CNB). Eight selected cognitive domains namely abstraction and mental flexibility, attention, face memory, spatial memory, working memory, spatial ability, sensorimotor and emotional processing known to be impaired among patients with SZ were measured. Whole exome sequencing of the study cohort was performed and data were processed using standard tools and software.  To identify variants/genes associated with cognitive domains, we performed two different levels of association testing: 1) linear regression analysis using the common variants (MAF>0.01) and eight different domains of cognition; and 2) gene-level tests for rare variant (MAF<0.01) association using burden tests (CMC, CMC-Wald & Zeggini). We identified 11 common variants associated (P<10-7) with different cognitive domains, which withstood Bonferroni corrections and rare variant burden analysis identified four genes associated (P<10-7).  Genes identified by these two approaches and their implications for cognitive deficits will be presented

Evaluation of familial influences on the course and severity of schizophrenia among US and Indian cases

Background: Prior studies suggest familial (possibly genetic) influences on the course of schizophrenia. Aims: The aim of this study was to compare familial influences on the course and severity of schizophrenia in two independent samples. Method: Thirteen selected measures were compared among affected sibling pairs (ASPs) from Pittsburgh, USA and New Delhi, India (48 US pairs, 53 Indian pairs). For each ASP proband, an unrelated patient was selected randomly from a suitable pool of cases ascertained in the same study (Sibpair proband-comparison case or S-C pairs). Correlations between these pairs were compared. Results: The correlations varied by item and by site. Significant correlations for longitudinal course and pattern of severity were noted among the ASPs from USA, but did not remain significant following corrections for multiple comparisons. Comparisons between the correlations for ASPs and the S-C pairs, used to estimate familial effects, yielded trends for the ASP correlations to be numerically larger than the S-C correlations in both samples. Separate cross-site comparisons revealed several significant differences with regard to several demographic and clinical variables. The possible impact of the cross-site variations on the observed ASP correlations is discussed. Conclusions: Though familial factors did not appear to have a significant impact on course/severity using this novel design, the suggestive trends need to be examined in larger samples

Phenotypic characterization of subjects with Crohn’s disease.

<p>Phenotypic characterization of subjects with Crohn’s disease.</p