Transcriptome association studies of neuropsychiatric traits in African Americans implicate PRMT7 in schizophrenia.

Peter N. Fiorica,Heather E. Wheeler

doi:10.7717/peerj.7778

Abstract

In the past 15 years, genome-wide association studies (GWAS) have provided novel insight into the genetic architecture of various complex traits; however, this insight has been primarily focused on populations of European descent. This emphasis on European populations has led to individuals of recent African descent being grossly underrepresented in the study of genetics. With African Americans making up less than 2% of participants in neuropsychiatric GWAS, this discrepancy is magnified in diseases such as schizophrenia and bipolar disorder. In this study, we performed GWAS and the gene-based association method PrediXcan for schizophrenia (n = 2,256) and bipolar disorder (n = 1,019) in African American cohorts. In our PrediXcan analyses, we identified PRMT7 (P = 5.5 × 10−6, local false sign rate = 0.12) as significantly associated with schizophrenia following an adaptive shrinkage multiple testing adjustment. This association with schizophrenia was confirmed in the much larger, predominantly European, Psychiatric Genomics Consortium. In addition to the PRMT7 association with schizophrenia, we identified rs10168049 (P = 1.0 × 10−6) as a potential candidate locus for bipolar disorder with highly divergent allele frequencies across populations, highlighting the need for diversity in genetic studies.

Highlights

Individuals of recent African ancestry have been grossly underrepresented in genomic studies
One of the largest genome-wide association studies (GWAS) of schizophrenia in an African American population was completed by the Genetic Association Information Network (GAIN) (Manolio et al, 2007); this study found no single nucleotide polymorphisms (SNPs) to be genome-wide significant and offered little insight into the potential function of genes in schizophrenia in African Americans
Schizophrenia gene-based association study To better understand the genetic architecture of schizophrenia in African Americans, we performed transcriptome-wide association studies using prediction models built in 55 tissues

Summary

Introduction

Individuals of recent African ancestry have been grossly underrepresented in genomic studies. Transcriptome association studies of neuropsychiatric traits in African Americans implicate PRMT7 in schizophrenia. Despite similar incidences of schizophrenia across European and African ancestry populations (De Candia et al, 2013; Whiteford et al, 2013), Africans have been predicted to have significantly less disease risk than their European counterparts using current GWAS summary statistics (Martin et al, 2017). In an attempt to address this discrepancy in genetic risk prediction, we performed a series of genetic association tests for schizophrenia and bipolar disorder in two cohorts of African American individuals (Manolio et al, 2007; Suarez et al, 2006; Smith et al, 2009)

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Discussion

Conclusion