Passchier Ruth V, Stein Dan J, Uhlmann Anne, van der Merwe Celia, Dalvie Shareefa
SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Department of Child and Adolescent Psychiatry and Psychotherapy, TU Dresden, Dresden, Germany.
Front Genet. 2020 Oct 2;11:1018. doi: 10.3389/fgene.2020.01018. eCollection 2020.
The genetic architecture of psychotic disorders is complex, with hundreds of genetic risk loci contributing to a polygenic model of disease. Overlap in the genetics of psychotic disorders and brain measures has been found in European populations, but has not been explored in populations of African ancestry. The aim of this study was to determine whether a relationship exists between a schizophrenia-derived PRS and (i) methamphetamine associated psychosis (MAP), and (ii) brain structural measures, in a South African population.
The study sample consisted of three participant groups: 31 individuals with MAP, 48 with apsychotic methamphetamine dependence, and 49 healthy controls. Using PRSice, PRS was generated for each of the participants with GWAS summary statistics from the Psychiatric Genomics Consortium Schizophrenia working group (PGC-SCZ2) as the discovery dataset. Regression analyses were performed to determine associations of PRS, with diagnosis, whole brain, and regional gray and white matter measures.
Schizophrenia-derived PRS did not significantly predict MAP diagnosis. After correction for multiple testing, no significant associations were found between PRS and brain measures across all groups.
The lack of significant associations here may indicate that the study is underpowered, that brain volumes in MAP are due to factors other than polygenic risk for schizophrenia, or that PRS derived from a largely European discovery set has limited utility in individuals of African ancestry. Larger studies, that include diverse populations, and more nuanced brain measures, may help elucidate the relationship between schizophrenia-PRS, brain structural changes, and psychosis.
This research presents the first PRS study to investigate shared genetic effects across psychotic disorders and brain structural measures in an African population. Ancestrally comparable discovery datasets may be useful for future African genetic research.
精神障碍的遗传结构复杂，数百个遗传风险位点促成了疾病的多基因模型。在欧洲人群中已发现精神障碍遗传学与脑测量之间存在重叠，但尚未在非洲裔人群中进行探索。本研究的目的是确定在南非人群中，源自精神分裂症的多基因风险评分（PRS）与（i）甲基苯丙胺所致精神病（MAP）以及（ii）脑结构测量之间是否存在关联。
研究样本包括三个参与者组：31名患有MAP的个体、48名患有非精神病性甲基苯丙胺依赖的个体以及49名健康对照。使用PRSice，以精神疾病基因组学联盟精神分裂症工作组（PGC-SCZ2）的全基因组关联研究（GWAS）汇总统计数据作为发现数据集，为每个参与者生成PRS。进行回归分析以确定PRS与诊断、全脑以及区域灰质和白质测量之间的关联。
源自精神分裂症的PRS不能显著预测MAP诊断。在进行多重检验校正后，所有组中PRS与脑测量之间均未发现显著关联。
此处缺乏显著关联可能表明该研究的效能不足，MAP中的脑容量是由精神分裂症多基因风险以外的因素导致的，或者源自主要为欧洲发现集的PRS在非洲裔个体中的效用有限。纳入更多样化人群和更细致脑测量的更大规模研究，可能有助于阐明精神分裂症-PRS、脑结构变化与精神病之间的关系。
本研究首次在非洲人群中进行了PRS研究，以调查精神障碍与脑结构测量之间的共享遗传效应。具有可比祖先的发现数据集可能对未来的非洲基因研究有用。
