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Transforming the understanding
and treatment of mental illnesses.

Ancestral Populations Network (APN)

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Psychiatric disorders are a significant global public health concern. However, most genome-wide studies to date have focused only on people of European ancestry. Diversity in genomic studies is key to obtaining more rigorous and comprehensive results that will allow the field to unravel the full genetic architecture of complex neuropsychiatric traits. To fully understand causal variants in mental health disorders, non-European ancestry populations in genetic studies should be included.

To address this gap and work toward global mental health equity, the National Institute of Mental Health established the Ancestral Populations Network in 2020. The APN was established through two funding announcements:

The overarching goals of the APN are to:

  1. Accelerate genetic discovery for psychiatric disorders in cohorts of non-European ancestry
  2. Advance global mental health discovery and equity
  3. Facilitate measurement and data analytic harmonization efforts to enhance rigor and reproducibility
  4. Generate a resource for APN members and the scientific community

Ancestral Populations Network Map 2023

The APN currently includes seven distinct projects with more than 100 investigators across 25 sites worldwide. The map below shows the countries (shaded) included in APN projects.

 

 
 
 

Countries:  Mexico, USA

Principal investigators and grants:

  • David Glahn, Ph.D. (U01MH124962 )
  • Laura Almasy, Ph.D.
  • Christopher Walsh, M.D., Ph.D.
  • Humberto Nicolini, M.D., Ph.D.

Principal investigators for grant R01MH133621  to continue the project:

  • David Glahn, Ph.D.
  • Laura Almasy, Ph.D.
  • Humberto Nicolini, M.D., Ph.D.
  • Carlos Bustamante, Ph.D.

Project overview:

This study aims to investigate the genetic architecture of psychotic illness using a severe clinical phenotype, early onset psychosis (EOP), in a pediatric sample recruited via the Navarro Hospital in Mexico City. The team will collect a sample of 6,600 subjects (including probands, family members, matched psychiatric nonpsychotic controls and non-psychiatric matched controls), to create the largest early onset psychosis resource to date.

Sample characterization will include deep phenotyping with collection of social determinants of health measures and additional environmental exposure measures. These will be added to blended genome and exome sequencing for all subjects to enhance our understanding of risk factors with a special focus on the Mexican population currently underrepresented in psychiatric genetic studies.

Countries:  Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, USA

Principal investigators and grants:

Project overview:

This study seeks to understand how genetic factors influence the risk of developing obsessive-compulsive disorder (OCD) in Latin American individuals by:

  • Collecting the world’s largest ancestrally- diverse sample of OCD cases (N = 5,000)
  • Detailing clinical characterization including comorbidities and OCD symptom dimensions
  • Genotyping all 5,000 samples (genotypes for >10,000 matched controls will be available). This, along with collaboration with other ongoing efforts, will allow us to discover genomic loci harboring common variation associated with OCD.
  • Calculating individual polygenic risk scores as a measure of genetic liability to OCD.

The project expects that the new inclusion of ancestrally diverse samples will yield more accurate polygenic risk scores in non-European samples and ultimately will reduce health disparities when OCD genomic findings are used clinically.

Countries:  South Korea, USA

Principal investigators and grants:

  • Jonathan Flint, M.D., (U01MH126798 )
  • Kenneth Kendler, M.D.
  • Yong Min Ahn M.D. Ph.D

Project overview:

The focus of this study is genetic characterization of a deeply phenotyped cohort of South Korean women with severe recurrent depression (MDD). The project aims to collect, deeply phenotype, and genotype 10,000 cases and 10,000 matched controls. Deep phenotyping will include extensive clinical interviews and collection of individual environmental exposure factors to further facilitate characterization of depression subtypes and environmental influences. Data from this study will be further meta analyzed with other cohorts of relevance to enhance the utility of this uniquely created resource.

Countries:  Brazil, Colombia, Ethiopia, Kenya, Nigeria, Uganda, South Africa, USA

Principal investigators and grants:

  • Benjamin Neale, Ph.D. (U01MH125047 )
  • Alicia Martin, Ph.D.
  • Karestan Koenen, Ph.D. (U01MH125045 )
  • Carlos Pato, M.D., Ph.D. (U01MH125049 )
  • Michele Pato, M.D.
  • Nelson Freimer, M.D. (U01MH125042 )
  • Carlos López-Jaramillo M.D., Ph.D.
  • Loes Olde Loohuis, Ph.D.
  • Roel Ophoff, Ph.D.

Project overview:

This project aims to expand upon prior NIMH-supported efforts of genetic characterization of serious mental illness (SMI), including schizophrenia and bipolar disorder, from Africa, South America, and the United States.

The team is currently recruiting 17,000 cases and 16,500 controls to build a total sample of 183,500 (88,860 cases and 94,900 matched controls). They will use the newly-developed Blended Genome Exome (BGE) sequencing technology, developed by members of the group, to sequence and analyze 40,000 schizophrenia cases, 40,000 bipolar disorder cases, and 40,000 matched controls from the collected African, Native American, and admixed ancestries. The project aims to create the largest to date phenotypic and genomic resource of non-European SMI data.

Countries:  South Africa, USA

Principal investigators and grants:

Project overview:

The goal of this international collaborative project is to characterize the genetic architecture of schizophrenia in the Xhosa population of South Africa.

The initial study of this group (Gulsuner at al., Science, 2020) was the first large-scale genetic study of schizophrenia in an ancestral African population. The main discovery was that Xhosa individuals with schizophrenia have a higher occurrence of rare, damaging mutations in genes involved in synaptic functioning.

The group is now enrolling an additional 1,250 cases and 1,250 age- and gender-matched controls, all Xhosa-speaking, to bring the total study population to 5,425 participants.

The project will apply new genomic technology (long-read whole genome sequencing) to identify previously undetectable classes of mutations likely to be implicated in schizophrenia.

Countries:  Brazil, Colombia, Peru, USA

Principal investigators and grants:

  • Joseph Buxbaum, Ph.D. (R01MH128813 )
  • Maria Rita dos Santos e Passos Bueno, Ph.D.
  • Bernie Devlin, Ph.D.
  • Maria Claudia Lattig, Ph.D.

Project overview:

This project is investigating the genetic risk for autism spectrum disorder (ASD) in people of Hispanic/Latinx ancestry.

The project is currently recruiting and phenotyping a new sample of 1,600 Hispanic/Latinx ASD trios (mother, father and affected child) to expand the existing sample set of well-characterized Hispanic/Latinx ASD samples to approximately 3,000. The project will genotype and sequence all samples in the cohort and combine results with the Autism Sequencing Consortium and the Psychiatric Genomics Consortium, which are large-scale, ongoing efforts on rare and common genetic variation, respectively.

At the successful conclusion of the proposed study, the group hopes to have contributed to a deeper understanding of how rare and common genetic variation contribute to risk for ASD across ancestries; better, more portable phenotype risk scores for diverse ancestries; and a larger number of known ASD risk genes. In addition, the project will have contributed to improving methods for integrating samples of diverse ancestry in genomic studies and will have enhanced recruitment of under-represented populations in such studies.

Countries:  India, Pakistan, Singapore, South Korea, Taiwan, USA

Principal investigators and grants:

Project overview:

This proposal brings together an international collaboration of leading investigators from the United States, 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 bipolar disorder in East and South Asia.

The project plans to recruit and deeply phenotype 17,500 bipolar disorder cases, with a focus on Bipolar-I (BP-I) to maximize homogeneity, and 14,000 controls from four Asian countries.

The project will carry out Whole Genome Sequencing on all recruited samples, plus 10,000 BP-I cases and 2,000 controls collected by a previous study using similar procedures in Pakistan. It will also conduct a range of analyses to discover new genetic associations with BP-I in East and South Asian populations, examine the comparative genetic architecture of BP-I across major world populations, and with other major neuropsychiatric disorders.

This proposal will dramatically increase the worldwide diversity of genetics data on bipolar disorder, an important step to accelerate gene discovery in this disorder and advance global mental health equity.

APN organization

APN is headed by two elected leaders and a Network Council, which consists of representatives from each Network site. These representatives vote to determine Network-wide policies and actions.

APN Leadership

Headshot of Loes Olde Loohuis, Ph.D.

Loes Olde Loohuis, Ph.D.

Assistant Professor in Psychiatry, Biobehavioral Sciences and Human Genetics at the University of California Los Angeles

Headshot of Benjamin Neale, Ph.D.

Benjamin Neale, Ph.D.

Co-director of the Program in Medical and Population Genetics at the Broad Institute and Director of Genetics at the Stanley Center for Psychiatric Research

NIMH APN Support Team

Headshot of Miri Gitik, Ph.D.

Miri Gitik, Ph.D.
APN Program Officer
Genomics Research Branch (GRB)
Division of Neuroscience and Basic Behavioral Science (DNBBS)
National Institute of Mental Health (NIMH)
Email: miri.gitik@nih.gov

Headshot of Andrea Horvath Marques, M.D., Ph.D., M.P.H.

Andrea Horvath Marques, M.D., Ph.D., M.P.H.
APN Project Scientist
Center for Global Mental Health Research (CGMHR)
National Institute of Mental Health (NIMH)
Email: andrea.horvathmarques@nih.gov

Headshot of Laura Rowland, Ph.D.

Laura Rowland, Ph.D.
APN Project Scientist
Division of Translational Research (DTR)
National Institute of Mental Health (NIMH)
Email: laura.rowland@nih.gov

Headshot of Lora Bingaman

Lora Bingaman
APN Program Analyst
Genomics Research Branch (GRB)
Division of Neuroscience and Basic Behavioral Science (DNBBS)
National Institute of Mental Health (NIMH)
Email: lora.bingaman@nih.gov

Collaborative working groups

Social Determinants of Health Group

This group is responsible for facilitating a comprehensive discussion regarding the impact of social determinants of health on genomic research and establishing a concise and user-friendly protocol for collecting standardized social determinant data into genetic studies particularly within diverse settings around the globe. In addition, this workgroup aims to promote analyses across different APN groups that focus on the dynamic interplay between genetics and societal factors.

Group leadership:

Ary Gadelha, Ph.D. (University of Sao Paulo, Brazil)

David Glahn, Ph.D. (Boston Children’s Hospital, U.S.A.)

Capacity Building Group

This group is working on shaping the policies and practices pertaining to building human capital by assessing and defining needs, challenges, and strengths of the groups in the Network, curating and developing training materials, and suggesting best practices as they relate to equitable collaborations.

Group leadership:

Lori Chibnik, Ph.D.(Harvard University/Broad Institute, U.S.A.)

Lukoye Atwoli, M.B.S., Ph.D., M.Med. Psych. (Aga Khan University, Kenya)

Ethics Group

This group is focused on best practices across four workstreams: Community Engagement, Equity in Global Collaborations, Informed Consent and the Decisional Capacity Process, and Ethics Committee Mapping.

Group leadership:

Anne Stevenson, M.Sc. (Harvard University/Broad Institute, U.S.A.)

Carlos Lopez-Jaramillo, M.D., Ph.D. (Universidad de Antioquia, Colombia)

Phenotype Harmonization Group

This group is working to collect and harmonize different measures for incorporation into genomic analyses. Developing resources evaluating the compatibility of different instruments across the Network.

Group leadership:

Eric Storch, Ph.D. (Baylor College of Medicine, U.S.A.)

Bizu Gelaye, Ph.D., M.P.H. (Harvard University, U.S.A.)

Genomic Harmonization Group

This group is working on genomic profiling evaluation across the network and standardizing the processing of genomic datasets to ensure integrability across the network.

Group leadership:

Elizabeth Atkinson, Ph.D. (Baylor College of Medicine, U.S.A.)

Alicia Martin, Ph.D. (Broad Institute, U.S.A.)

Genetic Concepts Group

This group is responsible for suggesting, facilitating, and helping to coordinate testing of genetic hypotheses collaboratively across multiple sites.

Group leadership:

Mary-Claire King, Ph.D. (University of Washington, U.S.A.)

Anthony Zohgbi, M.D. (Baylor College of Medicine, U.S.A.)

Publications

  1. J.M. McClellan*, Anthony W. Zoghbi*, Joseph D. Buxbaum, Carolina Cappi, James J. Crowley, Jonathan Flint, Dorothy E. Grice, Suleyman Gulsuner, Conrad Iyegbe, Sanjeev Jain, Po-Hsiu Kuo, Maria Claudia Lattig, Maria Rita Passos-Bueno, Meera Purushottam, Dan J. Stein, Anna B. Sunshine, Ezra S. Susser, Christopher A. Walsh, Olivia Wootton and Mary-Claire King. An evolutionary perspective on complex neuropsychiatric disease. Neuron. 2023 Nov 27:S0896-6273(23)00842-5. doi: 10.1016/j.neuron.2023.10.037. PMID: 38016473 * These authors contributed equally.
  2. Bitta, Mary ; Thungana, Yanga ; Kim, Hannah H ; Denckla, Christy A ; Ametaj, Amantia ; Yared, Mahlet ; Kwagala, Claire ; Ongeri, Linnet ; Stroud, Rocky E ; Kwobah, Edith ; Koenen, Karestan C ; Kariuki, Symon ; Zingela, Zukiswa ; Akena, Dickens ; Newton, Charles ; Atwoli, Lukoye ; Teferra, Solomon ; Stein, Dan J ; Gelaye, Bizu. Cross-country variations in the reporting of psychotic symptoms among sub-Saharan African adults: A psychometric evaluation of the Psychosis Screening Questionnaire. J Affect Disord. . 2022 May 1:304:85-92. doi: 0.1016/j.jad.2022.02.048. Epub 2022 Feb 18. PMID: 35183621
  3. Korte KJ, Jaguga, F, Kim H, Stroud, RE, Stevenson A, Akena D., Atwoli L, Gichuru, S, James R, Kwobah E, Kariuki S, Kyebuzibwa J, Mweme RM, Newton CRJC, Zingela Z, Stein DJ, Alemayehu M, Teferra, S, Koenen, KC & Gelaye B. Psychometric properties of the Mini International Neuropsychiatric Interview (MINI) Psychosis Module: A sub-Saharan Africa cross country comparison. Psychol Med . 2023 Nov;53(15):7042-7052. doi: 10.1017/S0033291723000296. Epub 2023 Mar 10. PMID: 36896802.
  4. Anne Stevenson, Marine Beltran, Supriya Misra, Amantia A. Ametaj, Aletta Bronkhorst, Bizu Gelaye, Karestan C. Koenen, Adele Pretorius, Dan J. Stein, Zukiswa Zingela. Trauma Exposure and Psychometric Properties of the Life Events Checklist among Adults in South Africa. Eur J Psychotraumatol . 2023;14(1):2172257. doi: 10.1080/20008066.2023.2172257. PMID: 37052114

Contact us

For more information about the APN, please contact:

Miri Gitik, Ph.D.
APN Program Officer
miri.gitik@nih.gov

Lora Bingaman
APN Program Analyst
lora.bingaman@nih.gov