van der Walt Kristien, Campbell Megan, Stein Dan J, Dalvie Shareefa
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics. Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
World J Biol Psychiatry. 2023 Apr;24(4):280-291. doi: 10.1080/15622975.2022.2099970. Epub 2022 Jul 29.
To summarise SNP associations identified by genome-wide association studies (GWASs) of anxiety disorders and neuroticism; to appraise the quality of individual studies, and to assess the ancestral diversity of study participants.
We searched PubMed, Scopus, PsychInfo and PubPsych for GWASs of anxiety disorders, non-diagnostic traits (such as anxiety sensitivity), and neuroticism, and extracted all SNPs that surpassed genome-wide significance. We graded study quality using Q-genie scores and reviewed the ancestral diversity of included participants.
32 studies met our inclusion criteria. A total of 563 independent significant variants were identified, of which 29 were replicated nominally in independent samples, and 3 were replicated significantly. The studies had good global quality, but many smaller studies were underpowered. Phenotypic heterogeneity for anxiety (and less so for neuroticism) seemed to reflect the complexity of capturing this trait. Ancestral diversity was poor, with 70% of studies including only populations of European ancestry.
The functionality of genes identified by GWASs of anxiety and neuroticism deserves further investigation. Future GWASs should have larger sample sizes, more rigorous phenotyping and include more ancestrally diverse population groups.
总结焦虑症和神经质的全基因组关联研究（GWAS）所确定的单核苷酸多态性（SNP）关联；评估个体研究的质量，并评估研究参与者的祖先多样性。
我们在PubMed、Scopus、PsychInfo和PubPsych中搜索焦虑症、非诊断性特质（如焦虑敏感性）和神经质的GWAS，并提取所有超过全基因组显著性的SNP。我们使用Q-genie评分对研究质量进行分级，并审查纳入参与者的祖先多样性。
32项研究符合我们的纳入标准。共鉴定出563个独立的显著变异，其中29个在独立样本中得到名义上的重复，3个得到显著重复。这些研究具有良好的整体质量，但许多较小的研究样本量不足。焦虑的表型异质性（神经质的表型异质性较小）似乎反映了捕捉该特质的复杂性。祖先多样性较差，70%的研究仅纳入欧洲血统人群。
焦虑症和神经质的GWAS所鉴定基因的功能值得进一步研究。未来的GWAS应该有更大的样本量、更严格的表型分型，并纳入更多祖先多样性的人群组。
