Genetically predicted high serum sex hormone-binding globulin levels are associated with lower ischemic stroke risk: A sex-stratified Mendelian randomization study.
J Stroke Cerebrovasc Dis
; 33(6): 107686, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38522757
ABSTRACT
OBJECTIVE:
Cross-sectional and cohort studies have found insufficient evidence of a causal relationship between sex hormone-binding globulin and ischemic stroke, only associations. Here, we performed a sex-stratified, bidirectional, two-sample Mendelian randomization analysis to evaluate whether a causal relationship exists between sex hormone-binding globulin and ischemic stroke.METHODS:
Single-nucleotide polymorphisms associated with sex hormone-binding globulin and ischemic stroke were screened from genome-wide association studies summary data as instrumental variables to enable a bidirectional, two-sample Mendelian randomization study design. Inverse-variance weighted analysis was used as the main method to evaluate potential causality, and additional methods, including the weighted median and MR-Egger tests, were used to validate the Mendelian randomization results. Cochran's Q statistic, MR-Egger intercept test, and Mendelian Randomization-Pleiotropy Residual Sum and Outlier global test were used as sensitivity analysis techniques to assure the reliability of the results. Multivariable analysis was used to show the robustness of the results with key theorized confounders.RESULTS:
Inverse-variance weighted analysis showed that genetically predicted higher serum sex hormone-binding globulin levels were associated with significantly decreased risk of ischemic stroke in males (odds radio = 0.934, 95 % confidence interval = 0.885-0.985, P = 0.012) and females (odds radio = 0.924, 95 % confidence interval = 0.868-0.983, P = 0.013). In an analysis of ischemic stroke subtypes, genetically predicted higher serum sex hormone-binding globulin levels were also associated with significantly decreased risk of small-vessel occlusion in both males (odds radio = 0.849, 95 % confidence interval = 0.759-0.949, P = 0.004) and females (odds radio = 0.829, 95 % confidence interval = 0.724-0.949, P = 0.006). The association remained in sensitivity analyses and multivariable analyses. The reverse analysis suggested an association between genetically predicted risk of cardioembolism and increased serum sex hormone-binding globulin in females (Beta = 0.029 nmol/L, Standard Error = 0.010, P = 0.003).CONCLUSION:
Our findings provide new insight into the etiology of ischemic stroke and suggest that modulating serum sex hormone-binding globulin may be a therapeutic strategy to protect against ischemic stroke.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Globulina de Unión a Hormona Sexual
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Biomarcadores
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Predisposición Genética a la Enfermedad
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Polimorfismo de Nucleótido Simple
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Estudio de Asociación del Genoma Completo
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Análisis de la Aleatorización Mendeliana
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Accidente Cerebrovascular Isquémico
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
J Stroke Cerebrovasc Dis
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J. stroke cerebrovasc. dis
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Journal of stroke and cerebrovascular diseases
Asunto de la revista:
ANGIOLOGIA
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CEREBRO
Año:
2024
Tipo del documento:
Article
País de afiliación:
China