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

3/4 亚洲双相遗传学网络（A-BIG-NET）

• 批准号: 10705721
• 负责人: Peter P. Zandi
• 金额: $ 20.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-16 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705721
• 关键词: Acceleration; Adopted; Adult; Alleles; Asia; Asian; Asian Americans; Asian ancestry; Asian population; Bipolar Disorder; Clinical; Collaborations; Complement; Consensus; Country; DNA; Data; Disease; East Asian; Environmental Risk Factor; Equity; European; European ancestry; Funding; Gene Frequency; Genetic; Genetic Diseases; Genetic Research; Genetic Variation; Genetic study; Genomics; Genotype; India; International; Joints; Maps; Measures; Mental Health; Mental disorders; Modeling; Molecular; Molecular Genetics; National Institute of Mental Health; Nature; Outcome; Pakistan; Pathogenesis; Phenotype; Play; Population; Prevalence; Procedures; Process; Production; Protocols documentation; Public Health; Publications; Quality Control; Records; Reduce health disparities; Reporting; Research; Research Personnel; Research Project Grants; Resources; Role; Sampling; Sampling Studies; Schizophrenia; Singapore; Site; South Asian; South Korea; Taiwan; Time; Uncertainty; Variant; Work; causal variant; cohort; comparative; data archive; data collection site; disorder subtype; environmental stressor; experience; field study; gene discovery; genetic architecture; genetic association; genetic resource; genetic risk factor; genetic signature; genetic variant; genome sequencing; genomic data; genomic locus; health care disparity; health disparity; health equity; insight; neuropsychiatric disorder; novel; phenotypic data; pleiotropism; polygenic risk score; psychiatric genomics; psychogenetics; rare variant; recruit; severe psychiatric disorder; web portal; whole genome

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 equity.

项目总结