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Approved Research

Indian Schizophrenia Genome-wide association study - Phase 2

Principal Investigator: Professor Bryan Mowry
Approved Research ID: 64593
Approval date: November 10th 2020

Lay summary

Aims.

1. To increase our already collected southern Indian dataset with genetic data from Indian ancestry UK Biobank healthy controls in order to increase sample size and thereby discover additional genetic findings for schizophrenia.

2. To attempt to replicate our findings in other major world ancestry datasets available via our membership of the Psychiatric Genomics Consortium (PGC).

Scientific rationale.

Although Indians constitute ~20% of the world's population, they are perhaps the least represented population in genetic studies. This is the case across the disease spectrum, and is nowhere more obvious than in psychiatric disorders, in particular schizophrenia. Most schizophrenia genetic findings have been discovered in European and more recently East Asian genome-wide association studies (GWAS). There is a need to survey other major world populations in order to enrich the global diversity of genetic findings for this disease. The outcome will contribute to the advancement of schizophrenia research in people of South Asian ancestry (25% of the global population).

Professor Mowry has a 20-year collaboration with Professor Thara at the Schizophrenia Research Foundation, Chennai. We have recruited, diagnosed, and collected DNA samples on more than 6000 individuals from schizophrenia families, unrelated cases and controls. Our recent publication, JAMA Psychiatry (July 3, 2019), described the first schizophrenia GWAS conducted in an Indian population, identifying a gene for a rate-limiting enzyme in niacin metabolism. We need to replicate this finding in a larger Indian sample comprising additional in-house samples and UK Biobank healthy controls. We plan to genotype 1400 of our own samples and integrate these with our other samples (total n=~3500) and ~10,000 UK Biobank genotyped samples of south Asian ancestry. By increasing the sample size, we aim to discover additional genetic findings associated with schizophrenia risk. We will attempt to replicate these findings in a large PGC European and East-Asian ancestry dataset.

Project Duration.

3 years.

Public Health Impact

Our results will contribute to determining whether our niacin finding (see above) will be confirmed in a larger sample, and if so, whether it will be translatable to the clinic as a supplemental treatment. Moreover, this work will facilitate future South Asian schizophrenia collaborative projects to discover additional genetic findings for eventual translation into the clinic. Further, the generated Indian-specific GWAS results may be utilized for predicting the presence of disease in other south Asian schizophrenia studies.