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Family, twin and adoption studies have indicated the role of genetic and environmental factors in the etiology of schizophrenia (SZ) with perceptible heterogeneity and heritability has been estimated at ~80%. Genome-Wide Association Studies (GWAS) utilizing common variants from across the genome have identified large number of mostly non-coding common variants with small affects. Recent efforts using whole exome sequencing (WES) approach have identified a large number of rare de novo variants and a few family based studies have also helped identify some variants that segregated with disease phenotype. Sharing of such rare but highly penetrant variants/mutations, in different families is believed to be not by chance alone but may reflect the role of a few major pathways in the etiology of the disease. Such data generated from the genetically distinct north Indian population is hypothesized to be very informative in the ever-challenging risk variant search in SZ. Families (n=19) with multi member affected with SZ and diagnosis based on DSM IV criteria were recruited from Dr RML Hospital, New Delhi with written informed consent. The study was approved by institutional ethical committee of participating institutions. WES of three informative individuals from each of the families were done with Agilent V5+UTR exome target capture kit for capturing the regions and sequencing on Illumina Hiseq2000 platform in paired end mode. Data analysis and prioritization of the variants were performed using standard tools/software and protocols. Rare variants segregating in the families were screened for, in the sporadic SZ cohort using WES data generated for them. Our study identified a large number of rare variants in disease relevant genes, shared in all affected individuals in the respective families but not across families. All the genes were of notable relevance to disease biology. Most of the gene variants were broadly related to glutamatergic pathway supporting the well-known hypothesis of glutamatergic dysfunction in SZ development. They also confirmed genetic heterogeneity underlying this illness. Taken together, findings are expected to propel improved understanding of disease biology and consequently, improved therapeutic interventions.

Background The right to privacy—and the related professional duty of confidentiality—allows participants to limit others’ access to information about themselves while still benefiting from healthcare or benefiting others in research. Like the right to give informed consent, the right to privacy and the confidentiality of health information promote well-being and protect autonomy or self-determination. This paper reports the first empirical study in India of the beliefs and expectations of patients/participants, their relatives, and IEC members regarding privacy/confidentiality. Methods The first goal of this qualitative study was to evaluate how IEC/IRB members understand privacy-related obligations, how their institutions protect patient/participant privacy, as well as what IEC/IRB members believe patients/participants think. The second goal was to use thematic analysis to learn about the privacy-related views and values patients/participants hold. After informed consent, members of IEC/IRB (n=19) in New Delhi, patients or research participants (n=29) in a psychiatric clinical setting, and relatives accompanying those patients/participants (n=30) were interviewed based on interview guides. Interviews were transcribed, translated and thematic analyses were carried out. Results Data collection and analysis were integrated, with the interview guides being continually revised to explore newly emerging concepts and themes. Four themes were extracted: IEC/IRB members’ understanding of privacy-related obligations, regulations, and guidelines; measures to protect patient and research participant privacy and barriers to their implementation; differences between IEC/IRB members’ estimation of the value people placed on privacy protection and people's actual views. Discussion Analysis of semi-structured interviews revealed that IEC/IRB members sometimes underestimate the value patients/participants and relatives place on privacy protection. The recurrent themes identified in the study data indicate that it is mistaken to think that Indian patients and the public do not value privacy. Themes demonstrate that they make strategic choices about what sort of health information to share and with whom.

Overall Abstract One of the primary missions of the ISPG is to spread state-of-the-art research into the genetics of mental illness around the globe. In so doing, we strive to adhere to the highest standards of scientific practice, to learn about regional chances and challenges, and to foster collaborations across continents. To this end, the ISPG has established a standing committee, the Global Diversity Task Force, bringing together researchers from all continents. A major focus of the Task Force's work lies on the empowerment of early career investigators. Furthermore, the Task Force aims at identifying obstacles that impede researchers' access to funding and other resources needed for successful research. In this symposium, we will learn about the latest developments on these "frontiers' from researchers from Latin America, Africa, Eastern Europe, and Asia.

Background In pediatric genetic research, parents need to provide permission for their child's participation. Parents may view these decisions differently from their own participation. This paper focuses on a qualitative analysis of interviews conducted with parents whose children (autistic or intellectually disabled) were requested to participate in a genetic research study. Understanding how parents make decisions about enrolling their children in genetic research and what they think about receiving their children's individual genetic research results is important for developing effective and appropriate approaches for primary research recruitment. Methods All participants were parents of prospective participants of a genetic study. During the enrollment process, they were asked to participate in a genetic study for their children and informed consent was obtained. Irrespective of whether they agreed or refused to participate, they were asked to record an interview regarding their attitude towards their children's participation in genetic studies. A total of 70 parents were interviewed. The recorded interviews were based on an interview guide, were transcribed and translated into English. We used an iterative approach to the qualitative content analysis of the transcripts and thematic analysis was performed. Results On most of the structured questions, majority of the participants understood the elements of the informed consent. But in spite of written statement in the consent form to the contrary, many felt that refusal to participate might affect their treatment. While majority agreed that research data should be confidential, a substantial number opined that confidentiality of research data is not important. On qualitative analyses, significant themes regarding their attitudes towards research participation were: Research was a part of Government policies; Participation for self-interest; Pro-social interest; Expectation of prevention of illness for next generation; Consent is for trust only. The themes were further elaborated. Other themes were: understanding of genetic research, confidentiality and comprehension of informed consent. Discussion The study revealed different attitudes of parents with regard to genetic research participation. The reasons of participation ranged from prosocial interests to self-interests. Confidentiality and comprehension of informed consent were also predictors of participation in such studies.

Background Schizophrenia (SZ) is a chronic disabling brain disease that clusters in many families with estimated heritability of 64-88%, based on twin studies. Conventionally, family history of psychosis is the best predictor of risk but environmental and epigenetic factors are equally important. Recurrence risk calculation and stratifying risk may make recurrence more understandable while elucidating environmental risk factors. The present study was conceptualized to stratify the risk of schizophrenia in first degree relatives into above average, moderate and high risk categories so that it is easier for family members to understand their risk for SZ. Methods We recruited prospectively families (n=128) with at least one person affected with SZ and at least one healthy sibling or offspring (18-60 years of age) from OPD of a Government hospital after informed consent process. After ascertaining diagnosis detailed family history on Family Interview for Genetic Studies (FIGS) was obtained and environmental risk elicited. Based on previous studies reported in the literature, we used the beta coefficients for the different risk factors to derive an equation for susceptibility Y=β1x1+β2x2+β3x3+β4x4+β5x5 Where x1 = Type and number of affected members; x2 Age of at risk person;. x3 Gender of at risk individual; x4=Paternal age at conception; x5=Gender of the affected individual Male/Female. We applied this equation to data on each of the siblings and offspring of cases to obtain an “estimate of risk of illness”. Results The mean estimated risk was 5.615±0.337. The distribution of risk of the sample was high (n=19); moderate (n=75) and above average (n=34). The formula was validated against a separate set of sample which was recruited for other studies. The risk of already recruited first degree relative diagnosed with schizophrenia was in high or moderate category according to the formula. Discussion The study stratified the first degree relatives of schizophrenia probands into high, moderate and above average risk categories considering not only their family history but also other factors which affect susceptibility to schizophrenia. This formula is not meant for use in normal populations as the prevalence of schizophrenia is 1% but in families where already at least one person is affected the risk is known to be increased. Risk calculation is important and a fundamental element of genetic counseling.

Background Schizophrenia (SZ) is a common psychiatric disorder with a large genetic component but perceptible heterogeneity. This together with lesser known etiological environmental cues makes the study of this illness a continuing challenge globally. Association studies of common variants in a range of candidate genes or genome-wide, in sporadic SZ cohorts fail to explain total heritability paving way for newer strategies to be exploited. Among these, rare variant discovery and trans-ethnic studies are expected to hold promise. Further, familial forms of SZ with multiple affected members are hypothesised to harbor shared, rare but highly penetrant variants/mutations. This study focussed on investigating a few such families of Indian origin. Methods Of several patients/families diagnosed with SZ at Dr RML Hospital, New Delhi using DSM IV criteria and recruited following institutional ethical committee clearance and written informed consent, 25 families with three or more affected members were selected for whole exome sequencing. A minimum of three informative individuals from each of these families were sequenced using the Agilent V5+UTR exome target capture kit. Analysis of exome data and variant prioritisation were done using standard pipeline. Results We identified over eight rare variants including compound heterozygotes in previously reported and in novel, functionally relevant candidate genes segregating with disease in these families. Mutation screening in these genes among sporadic SZ cases of north Indian ancestry to assess their overall contribution to disease etiology is underway. Discussion Next generation sequencing technologies have greatly facilitated discovery genomics in both Mendelian disorders and complex traits. Besides likely improved insights into disease biology by ongoing pathway analysis, uncovering new disease associated genes may also offer an opportunity to identify potential novel therapeutic targets. These findings will be presented during the meeting.

Background Schizophrenia is a polygenic neuropsychiatric disorder wherein specific molecular or phenotypic markers have not been reported, with several promising findings but inconsistent replication. Nevertheless, different markers from chromosome 6, discussed repeatedly and reinforced by GWAS findings, remain the most promising leads. The present study was carried out to replicate the important GWAS findings (p Methods Schizophrenia cases (n=1035) and matched healthy controls (n=1035) were recruited at PGIMER-Dr.R.M.L. hospital. Controls included age and gender matched psychiatrically healthy adults and cord blood samples. Using Sequenome platform, 26 markers were evaluated. In a subset of the samples (n=173 cases; n=87 controls), 8 different cognitive domains were evaluated using the UPenn Computerized Neuropsychological Battery, for the markers. Results Three markers namely rs2064430 (p=0.04, OR= 1.14, CI=1.01-1.3, AHI), rs6932590 (p=0.05, OR= 0.85, CI=0.73-1.00, intergenic), rs6916921 (p=0.05,OR=1.19, CI=1.00-1.43, NFKBIL1) showed modest association to DSM IV schizophrenia diagnosis under allelic test of association while rs3130615 and rs6916394 showed genotypic (p=0.04, p=0.02) and recessive association (p=0.01, 0.05) but none withstood Bonferroni correction. The most significant 2 marker haplotype using PLINK sliding window came from four regions: 1) intergenic region -rs6932590|rs3800318 (TA, p=0.02) 2) HLADQA1 region- rs377763|rs9273012 (GA, p=0.04) and 3) TNF region- rs1800610|rs986475 (CC, p=0.03) 4) MICB region- rs3130615| rs2516489 (CG, p=0.04). Significant association was observed among cases for rs377763 (p = 1.54*10-6) with ‘Sensorimotor functioning’ domain of the battery. Discussion The present study, although reaffirms association of a few chromosome 6 markers to schizophrenia in this ethnically distinct North Indian population; was of far lower magnitude than p=10-8 seen in initial GWAS findings.