LED and HS have been funded by startup funds from Stanford and a pilot grant to LED from the Stanford Center for Clinical and Translation Research and Education (UL1 TR001085, PI Greenberg). LED has also been funded by Cohen Veterans Bioscience (CVB), and she is part of the CVB Working Group for PTSD Adaptive Platform Trial. BG has been funded by the NIH (R01-HD-059835, PI Williams) and CVB. HH has been funded by the NIH (NIH K01DK114379 and NIH R21AI139012), the Zhengxu and Ying He Foundation, and the Stanley Center for Psychiatric Research. MBR received funds from WPA Congress Mexico City 2018, Guayaquil CEPAM 2019, Asunción X CONGRESO LATINOAMERICANO DE LA FLAPB 2018, Guayaquil 2019 (Bago), and Lancet Psychiatry, London (commission on Violence against women) 2019. SS declares no potential conflict of interest. / Genome-wide approaches including polygenic risk scores (PRSs) are now widely used in medical research; however, few studies have been conducted in low- and middle-income countries (LMICs), especially in South America. This study was designed to test the transferability of psychiatric PRSs to individuals with different ancestral and cultural backgrounds and to provide genome-wide association study (GWAS) results for psychiatric outcomes in this sample. The PrOMIS cohort (N = 3308) was recruited from prenatal care clinics at the Instituto Nacional Materno Perinatal (INMP) in Lima, Peru. Three major psychiatric outcomes (depression, PTSD, and suicidal ideation and/or self-harm) were scored by interviewers using valid Spanish questionnaires. Illumina Multi-Ethnic Global chip was used for genotyping. Standard procedures for PRSs and GWAS were used along with extra steps to rule out confounding due to ancestry. Depression PRSs significantly predicted depression, PTSD, and suicidal ideation/self-harm and explained up to 0.6% of phenotypic variation (minimum p = 3.9 × 10−6). The associations were robust to sensitivity analyses using more homogeneous subgroups of participants and alternative choices of principal components. Successful polygenic prediction of three psychiatric phenotypes in this Peruvian cohort suggests that genetic influences on depression, PTSD, and suicidal ideation/self-harm are at least partially shared across global populations. These PRS and GWAS results from this large Peruvian cohort advance genetic research (and the potential for improved treatments) for diverse global populations. / National Institutes of Health / Revisión por pares

Gene set enrichment analysis aims to discover sets of genes, such as biological pathways or protein complexes, which may show moderate but coordinated differentiation across experimental conditions. The existing gene set enrichment approaches utilize single gene statistic as a measure of differentiation for individual genes. These approaches do not utilize any inter-gene correlations, but it has been known that genes in a pathway often interact with each other. Motivated by the need for taking gene dependence into account, we propose a novel gene set enrichment algorithm, where the gene-gene correlation is addressed via a gene-pair representation strategy. Relying on an appropriately defined gene pair statistic, the gene set statistic is formulated using a competitive null hypothesis. Extensive simulation studies show that our proposed approach can correctly control the type I error (false positive rate), and retain good statistical power for detecting true differential expression. The new method is also applied to analyze several gene expression datasets. / October 2016