Psychiatric genetics in the diverse landscape of Latin American populations

Abstract

Psychiatric disorders are highly heritable and polygenic, influenced by environmental factors and often comorbid. Large-scale genome-wide association studies (GWASs) through consortium efforts have identified genetic risk loci and revealed the underlying biology of psychiatric disorders and traits. However, over 85% of psychiatric GWAS participants are of European ancestry, limiting the applicability of these findings to non-European populations. Latin America and the Caribbean, regions marked by diverse genetic admixture, distinct environments and healthcare disparities, remain critically understudied in psychiatric genomics. This threatens access to precision psychiatry, where diversity is crucial for innovation and equity. This Review evaluates the current state and advancements in psychiatric genomics within Latin America and the Caribbean, discusses the prevalence and burden of psychiatric disorders, explores contributions to psychiatric GWASs from these regions and highlights methods that account for genetic diversity. We also identify existing gaps and challenges and propose recommendations to promote equity in psychiatric genomics.

Fig. 1.. Genetic diversity in Latin America.

Genetic ancestry of individuals from six Latin American and Caribbean countries (Mexico, Puerto Rico, Barbados, Colombia, Peru, and Brazil) based on data from the 1000 Genomes Project and the Human Genome Diversity Project (HGDP). The principal components analysis (PCA) plots illustrate genetic ancestry distribution patterns using the first two principal components (PC1 and PC2), which capture the largest fractions of ancestry variation. In the top PCA plot, individuals are arranged in a triangular pattern: the apex clusters those with predominantly European ancestry, the bottom left represents individuals with primarily African ancestry, and the bottom right corresponds to those with mainly East Asian ancestry. A degree of separation is observed among these three major groups. In contrast, the bottom PCA plot highlights samples from Latin America and the Caribbean, revealing a heterogeneous pattern. Individuals from this region are highly admixed, dispersing broadly across the PC1 and PC2 ancestry distributions. The continental map indicates the locations in Latin America and the Caribbean where the samples were collected. The data used to generate the plots were downloaded from gnomAD (https://gnomad.broadinstitute.org/).

Fig. 2.. Psychiatric genetics research in Latin America.

This figure highlights the progress and challenges in psychiatric genetics research in Latin American populations. (a) Bar plot comparing the prevalence of psychiatric disorders in Latin America, high-income North America, and globally, based on data from the Global Burden of Disease study (GBD 2021, VizHub at https://vizhub.healthdata.org/gbd-results/). (b) Chord diagram showing the relationship between GWASs and the countries and disorders studied, with most Latin American samples coming from the USA, and substance use being the most frequently researched psychiatric trait. (c) Scatter plot illustrating the sample size of GWAS studies in Latin American populations, showing that larger studies, such as those on substance use, have greater power to identify significant loci. Notes: Drug use disorder includes conditions involving opioids, amphetamines, cocaine, cannabis, and other drugs. SUD combines data from both alcohol and drug use disorders. ED include anorexia nervosa and bulimia nervosa. Abbreviations: GWAS: genome-wide association study; ADHD: Attention Deficit/Hyperactivity Disorder; AUD: Alcohol Use Disorder; BD: Bipolar Disorder; CUD: Cannabis Use Disorder; ED: Eating Disorder; MDD: Major Depressive Disorder; PTSD: Post-Traumatic Stress Disorder; OCD: Obsessive-Compulsive Disorder; OUD: Opioid Use Disorder; SCZ: Schizophrenia; SU/SUD: Substance Use and Substance Use Disorder; TUD: Tobacco Use Disorder.