Ancestral Populations Network (APN)

Countries:  South Africa, Uganda, USA

Principal investigators and grants:

• Kristy Donald, M.B.Ch.B., Ph.D. (R01MH132950 )

Project overview:

Genetic research into attention deficit hyperactivity disorder (ADHD) lags in terms of: (1) sample size, (2) ancestral diversity, and (3) consideration of phenotypic heterogeneity. The Akili project will address all three of these critical gaps, phenotypically and genetically characterizing 4,000 children with ADHD and 2,000 age- and ancestry-matched controls in Kenya and South Africa. All data and materials from Akili will be made publicly available through the NIMH, creating a research resource of international value.

Countries:  Brazil

Principal investigators and grants:

• Diego Luiz Rovaris, Ph.D. (R01MH131013 )

Project overview:

Attention-deficit/hyperactivity disorder (ADHD) is a worldwide prevalent neurodevelopmental condition causing impairments in several life contexts. People with ADHD are at increased risk for poor school performance, educational underachievement, and unemployment, which is related to the elevated economic burden of ADHD. The proposed research is relevant to public health because it will help to disentangle the biological mechanisms involved in the interplay between ADHD and educational attainment, and it was designed to decrease the Eurocentric bias seen in genomic and epigenomic studies in mental health.

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:

• James Crowley, Ph.D. (U01MH125050 )
• Manuel Mattheisen, M.D.
• Michele Pato, M.D.
• Eric Storch, Ph.D. (U01MH125062 )

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:  Kenya, South Africa, Uganda, UK, USA

Principal investigators and grants:

• Karestan Koenen, Ph.D. (R01MH134468 )
• Dickens Akena, M.B.Ch.B., M.Med.
• Lukoye Atwoli, M.B.B.S, M.Med., Ph.D.
• Segun Fatumo, Ph.D.
• Caroline Nievergelt, Ph.D.

Project overview:

Progress has been made in identifying genetic risk factors for PTSD. However, the under-representation of African populations in PTSD genetic research risks widening existing research and treatment disparities for such populations. The goal of this proposal is to accelerate genetic discovery for PTSD by addressing the under- representation of African populations in PTSD genetic research through a unique U.S. – African partnership which includes large-scale data collection, the long-term goal is to ensure the genomics revolution in psychiatry benefits future generations of Africans.

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:

• Mary-Claire King, Ph.D. (U01MH125054 )
• Suleyman Gulsuner, M.D., Ph.D.
• Jon M. McClellan, M.D.
• Tomas D. Walsh, Ph.D.
• Ezra Susser, M.D., Dr.Phil. (U01MH125058 )
• Dan Stein, Ph.D., D.Phil. (U01MH125053 )

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:

• Hailiang Huang, Ph.D. (R01MH130675-01 )
• Kenneth Kendler, M.D. (R01MH130665-01 )
• Peter Zandi, Ph.D. (R01MH130673-01 )
• Po-Hsiu Kuo, Ph.D. (R01MH130674-01 )

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.