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.

中文翻译：

---

秘鲁队列中抑郁症、创伤后应激障碍和自杀意念/自残的多基因预测和 GWAS。

包括多基因风险评分 (PRS) 在内的全基因组方法现已广泛用于医学研究；然而，很少有研究在低收入和中等收入国家（LMICs）进行，尤其是在南美洲。本研究旨在测试精神病学 PRS 对具有不同祖先和文化背景的个体的可转移性，并为该样本中的精神病学结果提供全基因组关联研究 (GWAS) 结果。PrOMIS 队列 (N = 3308) 是从秘鲁利马的国家孕产妇研究所 (INMP) 的产前保健诊所招募的。采访者使用有效的西班牙问卷对三种主要的精神病学结果（抑郁、创伤后应激障碍和自杀意念和/或自残）进行评分。Illumina Multi-Ethnic Global 芯片用于基因分型。使用 PRS 和 GWAS 的标准程序以及额外的步骤来排除由于血统引起的混淆。抑郁 PRS 显着预测抑郁、创伤后应激障碍和自杀意念/自残，并解释了高达 0.6% 的表型变异（最小 p = 3.9 × 10-6）。对于使用更同质的参与者亚组和主要成分的替代选择的敏感性分析，这些关联是稳健的。在这个秘鲁队列中对三种精神病学表型的成功多基因预测表明，遗传对抑郁症、创伤后应激障碍和自杀意念/自残的影响至少在全球人群中部分共享。这些 PRS 和 GWAS 来自这个庞大的秘鲁队列，为不同的全球人群推进了基因研究（以及改进治疗的潜力）。