AUTHOR=Jiang Junhao , Qin Zhuo , Yan Junxia , Liu Junyu 

TITLE=Methodological quality assessment of genetic studies on brain arteriovenous malformation related hemorrhage: A cross-sectional study

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1123898

DOI=10.3389/fgene.2023.1123898

ISSN=1664-8021

ABSTRACT=<p><bold>Objectives:</bold> Rupture of a brain arteriovenous malformation (bAVM) can cause intracranial hemorrhage and severe clinical outcomes. At present, the mechanisms of bAVM-related hemorrhage are poorly understood. This study aimed to summarize the potential genetic risk factors for bAVM-related hemorrhage and appraise the methodological quality of existing genetic studies on bAVM-related hemorrhage using a cross-sectional design.</p><p><bold>Methods:</bold> A systematic literature search was conducted on genetic studies associated with bAVM-related hemorrhage published in PubMed, Embase, Web of Science, China National Knowledge Internet, and Wangfang databases, up to November 2022. Subsequently, a cross-sectional study was performed to describe the potential candidate genetic variants of bAVM associated with risk of hemorrhage and to evaluate the methodological quality of the identified studies using the Newcastle–Ottawa quality assessment scale and Q-genie tool.</p><p><bold>Results:</bold> Of the 1811 records identified in the initial search, nine studies met the filtering criteria and were included. Twelve single nucleotide polymorphisms (SNPs), including <italic>IL6</italic> rs1800795, <italic>IL17A</italic> rs2275913, <italic>MMP9</italic> rs9509, <italic>VEGFA</italic> rs1547651, and <italic>EPHB4</italic> rs314353<italic>,</italic> rs314308, and rs314313, were associated with bAVM-related hemorrhage. However, only 12.5% of the evaluated SNPs showed statistical power&gt; 0.80 (<italic>α</italic> = 0.05). Methodological quality assessment revealed significant flaws in the designs of the included studies, such as less reliable representativeness of recruited individuals, short follow-up periods in cohort studies, and less comparability between groups of hemorrhagic and non-hemorrhagic patients.</p><p><bold>Conclusion:</bold><italic>IL1B</italic>, <italic>IL6</italic>, <italic>IL17A</italic>, <italic>APOE</italic>, <italic>MMP9</italic>, <italic>VEGFA</italic> and <italic>EPHB4</italic> were potentially associated with bAVM-related hemorrhage. The methodological designs of the analyzed studies required improvement in order to obtain more reliable results. Regional alliances and rare disease banks need to be established to recruit large numbers of bAVM patients (especially familial and extreme-trait cases) in a multicenter, prospective cohort study with an adequate follow-up period. Furthermore, it is important to use advanced sequencing techniques and efficient measures to filter candidate genetic variants.</p>