# 3/4 Asian Bipolar Genetics Network (A-BIG-NET)

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $204,688

## Abstract

PROJECT SUMMARY
Bipolar disorder (BP) is a severe multifactorial neuropsychiatric disorder that imposes a significant burden on
public health. The most recent large-scale genetic study of BP identified 64 associated genetic loci, providing
initial insights in BP pathogenesis. Yet, genetic discovery in BP lags behind other key psychiatric disorders. The
reported genetic loci only capture a small proportion of the total BP genetic liability, with many more variants
across the common and rare allele frequency spectrum remaining to be discovered. In addition, the previous
studied samples were of European ancestry, leaving population specific BP variants uncovered and uncertainty
in how the BP genetic findings generalize to other populations, exacerbating healthcare disparities, and these
studies rarely employed “deep” phenotyping or assessed relevant environmental risk factors. This proposal
brings together an international collaboration of leading investigators from the U.S., Taiwan, South Korea,
Singapore, India, and Pakistan to form the Asian Bipolar Genetics Network (A-BIG-NET) and carry out a large-
scale genetic study of BP in East and South Asia. A-BIG-NET will generate a BP genetic resource of 27,500
cases and 16,000 controls with rich phenotypic information, measures of key environmental stressors and
genetic data from 4x low-pass whole genome sequencing (4xWGS). This will complement a schizophrenia
genetics resource of 22,778 cases and 35,362 controls of Asian ancestry previously assembled by leaders of
this network that will be available for cross-disorder comparisons. Studying BP genetics in Asia is important to
the world and the U.S., as Asia constitutes 57% of the world population, and Asian American comprises 6.6% of
the U.S. population (21.4 million). The five countries in A-BIG-NET cover 35% of all Asian populations. The
specific aims of the proposal are to: 1) recruit and deeply phenotype 17,500 BP cases, with a focus on BP-I to
maximize homogeneity, and 14,000 controls from four Asian countries; 2) carry out 4xWGS on all recruited
samples plus 10,000 BP-I cases and 2,000 controls collected by a previous study using similar procedures in
Pakistan; and 3) carry out a range of analyses to discover new genetic associations with BP-I across the allelic
spectrum in East and South Asian populations, examine the comparative genetic architecture of BP-I across
major world populations and with other major neuropsychiatric disorders, and perform a novel statistical fine-
mapping analysis that leverages the multi-ancestry genomic diversity and pleiotropy across psychiatric disorders
to identify putative causal variants. Aim 3 will also explore the genetic “validity” of various BP-I subtypes and fit
models with joint genetic and environmental risk factors. This proposal will dramatically increase the worldwide
diversity of genetics data on BP, an important step to accelerate gene discovery in this disorder and advance
global mental health equit...

## Key facts

- **NIH application ID:** 10907596
- **Project number:** 5R01MH130673-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Peter P. Zandi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $204,688
- **Award type:** 5
- **Project period:** 2022-09-16 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907596

## Citation

> US National Institutes of Health, RePORTER application 10907596, 3/4 Asian Bipolar Genetics Network (A-BIG-NET) (5R01MH130673-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10907596. Licensed CC0.

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