# The GEN-SCRIP Study (GENetics of SChizophRenia in Pakistan)

> **NIH NIH R01** · SUNY DOWNSTATE MEDICAL CENTER · 2021 · $4,252

## Abstract

Schizophrenia affects about 1 percent of the world population. We do not currently understand the biological
underpinnings of schizophrenia well enough to design effective treatment strategies. Twin and adoption studies
supported a genetic etiology. It is becoming clear that its inheritance is partitioned between the rare and
common variants in hundreds of genes, each one having a small effect. The sample size required to elucidate
the genetic etiology of schizophrenia can be achieved through large scale collaborative efforts, which are
currently ongoing. A study published by Psychiatric Genomics Consortium in 2014 identified 108 Genome-
Wide significant loci associated for the disorder in samples with European ancestry. Although it was an
important milestone in schizophrenia genetics these loci only explain a small proportion of the genetic
variance.
Expansion of this approach in size, and to other population groups, is required to discovery of additional
genetic variants associated with schizophrenia. We propose to ascertain and collect 10,000 cases and 10,000
controls from Pakistan. We have already ascertained and collected 2,000 cases and 1,000 controls. We have
formed a consortium of Pakistani psychiatrists at 12 centers. These samples will be genotyped at Stanley
Center for Psychiatric Research with Illumina Global Screening Array (GSA), which will contain a backbone of
~660,000 SNPs, which provides LD coverage and imputation accuracy of >0.8, for over 87% of the South
Asian genome. There is a strong tradition of consanguineous marriages in Pakistan which has an advantage
for genetic studies, especially of recessively inherited traits. We will analyze these data for common SNPs,
haplotypes, and copy number variations (CNVs). In association analysis we will examine for recessive
inheritance, in addition to additive models of common variants to disease. We will perform a homozygosity
mapping to identify regions that are enriched for Runs of Homozygosity (ROH) in cases, as compared to
controls. This population will have a different linkage disequilibrium structure which will help to narrow down
the genomic intervals containing the potential causative variants at the 108 loci identified in the Caucasian
Genome Wide Association Study. We will share these data with broader scientific community via the
Psychiatric Genomics Consortium and dbGaP.

## Key facts

- **NIH application ID:** 10161831
- **Project number:** 5R01MH112904-05
- **Recipient organization:** SUNY DOWNSTATE MEDICAL CENTER
- **Principal Investigator:** JAMES A KNOWLES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $4,252
- **Award type:** 5
- **Project period:** 2017-07-15 → 2022-03-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161831

## Citation

> US National Institutes of Health, RePORTER application 10161831, The GEN-SCRIP Study (GENetics of SChizophRenia in Pakistan) (5R01MH112904-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10161831. Licensed CC0.

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