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Abstract：
Heritability is well documented for psychiatric disorders and cognitive abilities which are, however, complex, involving both genetic and environmental factors. Hence, it remains challenging to discover which and how genetic variations contribute to such complex traits. In this article, they propose to use mediation analysis to bridge this gap, where neuroimaging phenotypes were utilized as intermediate variables. The Philadelphia Neurodevelopmental Cohort was investigated using genome-wide association studies (GWAS) and mediation analyses. Specifically, 951 participants were included with age ranging from 8 to 21 years. Two hundred and four neuroimaging measures were extracted from structural magnetic resonance imaging scans. GWAS were conducted for each measure to evaluate the SNP-based heritability. Furthermore, mediation analyses were employed to understand the mechanisms in which genetic variants have influence on pathological behaviors implicitly through neuroimaging phenotypes, and identified SNPs that would not be detected otherwise. Our analyses found that rs10494561, located in the intron region within NMNAT2, was associated with the severity of the prodromal symptoms of psychosis implicitly, mediated through the volume of the left hemisphere of the superior frontal region ( P=2.38×10-8). The gene NMNAT2 is known to be associated with brainstem degeneration, and produce cytoplasmic enzyme which is mainly expressed in the brain. Another SNP rs2285351 was found in the intron region of gene IFT122 which may be potentially associated with human spatial orientation ability through the area of the left hemisphere of the isthmuscingulate region ( P=3.70×10-8). Hum Brain Mapp 38:4088-4097, 2017. © 2017 Wiley Periodicals, Inc.
摘要：
遗传力对于精神疾病和认知能力有很好的记录，然而,复杂，涉及遗传和环境因素。因此，发现哪种遗传变异以及如何导致这种复杂的特征仍然具有挑战性。在这篇文章中,他们建议使用调解分析来弥合这一差距，其中神经影像学表型被用作中间变量。使用全基因组关联研究（GWAS）和中介分析研究了费城神经发育队列。具体来说,纳入951名参与者，年龄从8岁到21岁不等。从结构磁共振成像扫描中提取了两百四个神经成像措施。对每个测量进行GWAS以评估基于SNP的遗传力。此外，中介分析被用来了解的机制，其中遗传变异有影响病理行为隐含地通过神经影像学表型。并鉴定了否则无法检测到的SNP。我们的分析发现，位于NMNAT2内含子区域的rs10494561与精神病前驱症状的严重程度有关，通过上额叶区左半球的体积介导（P=2.38×10-8）。NMNAT2基因已知与脑干变性有关，并产生主要在大脑中表达的细胞质酶。在基因IFT122的内含子区域中发现了另一个SNPrs2285351，该区域可能与人的空间定向能力有关，该空间定向能力通过峡部带区域的左半球区域（P=3.70×10-8）。HumBrainMapp38：4088-4097，2017。©2017Wiley期刊，Inc.
