# The GEN-BLIP Study (GENetics of BipoLar Disorder In Pakistan)

> **NIH NIH R01** · SUNY DOWNSTATE MEDICAL CENTER · 2020 · $637,011

## Abstract

ABSTRACT
Bipolar Disorder affects about 1 percent of the world population. We do not currently understand
the biological underpinnings of Bipolar Disorder well enough to design effective treatment
strategies. Twin and adoption studies support a genetic etiology and we now know this is
partitioned between both rare and common variants in hundreds of genes, each variant having a
small effect. The sample size required to more fully elucidate the genetic etiology of Bipolar
Disorder can only be achieved through large scale collaborative efforts. For instance, the 2018
Psychiatric Genomics Consortium (PGC) Bipolar Disorder Genome-Wide Association Study
(GWAS) discovered 30 significant loci using samples with European ancestry. Although this is
an important milestone in understanding the genetics of Bipolar Disorder, collectively these loci
only explain a small proportion of the genetic variance.
Expansion of this approach to other population groups, with adequate sample size, is required
to discovery of additional genetic variants associated with Bipolar Disorder. We propose to
ascertain and collect 10,000 cases and 2,000 controls from Pakistan. We currently have an
ongoing study in Pakistan (GEN-SCRIP) that will collect an additional 10,000 controls. We have
formed a consortium of Pakistani psychiatrists at 11 centers. The 12,000 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 30 loci identified in the PGC2 BP GWAS. We will share these
data with broader scientific community via the NIMH Genetics Repository and Genomic
Research, the Psychiatric Genomics Consortium and dbGaP.

## Key facts

- **NIH application ID:** 10034810
- **Project number:** 1R01MH123775-01
- **Recipient organization:** SUNY DOWNSTATE MEDICAL CENTER
- **Principal Investigator:** JAMES A KNOWLES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $637,011
- **Award type:** 1
- **Project period:** 2020-07-07 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10034810

## Citation

> US National Institutes of Health, RePORTER application 10034810, The GEN-BLIP Study (GENetics of BipoLar Disorder In Pakistan) (1R01MH123775-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10034810. Licensed CC0.

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