Latino Ancestry Genomic Psychiatry Cohort

Project Summary The Latino Ancestry-Genomic Psychiatry Cohort (LA-GPC) is an expansion of the GPC into the Latino population. LA and other minority populations have been poorly represented in large-scale genomic studies, and yet these populations (i) suffer the largest disparities in health care and outcomes, and (ii) have the potential to broaden our knowledge of human genetics. In particular, LA genomes are admixed and are characterized by different haplotype blocks than European ancestry (EA) populations. As a consequence, genetic polymorphisms that are in perfect linkage disequilibrium (LD) in Europeans may be broken-up by recombination events in LA genomes, allowing the contributions of different genomic intervals to be assessed independently. Progress to date: The GPC has enrolled and assessed over 5,000 new LA participants and we have recently published a pilot GWAS including both LA and African Ancestry (AA) participants. GWAS meta- analysis of PGC-SCZ2 with pilot results for 4,324 (cases and controls) LA-GPC participants yielded 8 new schizophrenia-associated risk loci, and for 9 loci there was a concomitant reduction in the number of SNPs in the associated interval. Crucially, the resultant cross-ancestry summary statistics, informed by multiple ancestrally diverse cohorts, yielded individual-level polygenic risk scores that explained more variance than analogous scores based on either ancestry alone In Phase 1 of this renewal: we will study genome-wide common variation in our existing LA-GPC and VA- CS#572 combined cohort of 16,124 LA participants. In Phase 2, we will perform an expanded analysis by adding 8,000 new participants ascertained in the LA-GPC, 35,000 additional participants from the VA, 8,000 participants from the NeuroMex study (PI. Koenen), and 10,000 participants from the Colombian study (PI. Freimer). This meta-analysis will include over 77,000 LA participants, a sample of non-Caucasians with the potential for significant novel discovery.