AUTHOR=Tian Yi , Shi Xiao Qin , Shui Jing Wen , Liu Xiao Yu , Bu Ya , Liu Yi , Yin Li Ping 

TITLE=Exploring the causal factor effects of hypothyroidism on ischemic stroke: a two-sample Mendelian randomization study

JOURNAL=Frontiers in Neurology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1322472

DOI=10.3389/fneur.2024.1322472

ISSN=1664-2295

ABSTRACT=<sec id="sec1"><title>Background</title><p>Observational studies have suggested a possible association between hypothyroidism and increased risk of ischemic stroke. However, a causal relationship remains unclear.</p></sec><sec id="sec2"><title>Methods</title><p>Data on single nucleotide polymorphisms (SNPs) associated with hypothyroidism and ischemic stroke were sourced from the FinnGens database and the UK Biobank of European descent. Both databases underwent separate two-sample Mendelian randomization (MR) analyses. A subsequent meta-analysis of MR results using a random-effects model was conducted to determine the causal relationship between hypothyroidism and ischemic stroke.</p></sec><sec id="sec3"><title>Results</title><p>All five analyses indicated a positive causal relationship between hypothyroidism and ischemic stroke. MR analysis of the association between hypothyroidism and ischemic stroke yielded a result of the inverse variance weighted (IVW) method at 4.7411 (1.3598–16.5308), <italic>p</italic> = 0.0146. The analysis of ischemic stroke (without excluding controls) yielded a result of the IVW method of 4.5713 (1.3570–15.3986), <italic>p</italic> = 0.0142. MR analysis with cerebral infarction yielded a result of the IVW method at 1.0110 (1.0006–1.0215), <italic>p</italic> = 0.0373. The MR analysis with cerebrovascular disease sequelae yielded an IVW method result of 2.4556 (1.0291–5.8595), <italic>p</italic> = 0.0429. Analysis for the sequelae of cerebrovascular disease (without excluding controls) yielded an IVW method result of 2.4217 (1.0217–5.7402), <italic>p</italic> = 0.0446. No evidence of heterogeneity or horizontal pleiotropy was found. The meta-analysis of the five MR results was 2.24 (1.18–4.26), <italic>p</italic> = 0.025.</p></sec><sec id="sec4"><title>Conclusion</title><p>Our two-sample Mendelian randomization study suggested a causal relationship between hypothyroidism and ischemic stroke, indicating that hypothyroidism could be a risk factor for ischemic stroke. However, further studies are required to elucidate the underlying biological mechanisms.</p></sec>