• Jia-Wen Xie, Yin-Feng Guo, Mao Wang, Man-Li Tong, Xiao-Zhen Zhu, and Li-Rong Lin.
• Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.
• Prev Med. 2024 Aug 1; 185: 108033108033.

ObjectiveThe pathogenic mechanisms of syphilis and the host defense mechanisms against syphilis remain poorly understood. Exploration of the susceptibility factors of syphilis may provide crucial clues for unraveling its underlying mechanisms.MethodsA two-sample Mendelian Randomization framework was utilized, and the inverse-variance weighted method was used as the main analysis. All data was sourced from Genome-wide association studies datasets from 2015 to 2022 in Europe, and all participants were of European descent. Only summary-level statistics were used. Sensitivity analyses were conducted to evaluate the heterogeneity and pleiotropy of the datasets.ResultsOur study established 18 exposure factors (12 risk factors and 6 protective factors) for syphilis susceptibility. Twelve factors encompassing body mass index, waist circumference, darker natural skin, cooked vegetable intake, processed meat intake, diabetes mellitus, glucose regulation disorders, gout, autoimmune diseases, rheumatoid arthritis, diverticulitis, and longer menstrual cycles were found to increase susceptibility to syphilis. In contrast, 6 factors including easier skin tanning, blonde natural hair color, irritability, higher neuroticism scores, extended sleep duration, and delayed age at first sexual intercourse were connected to a reduced risk of syphilis infection (all P < 0.05).ConclusionsThis study identified 18 influencing factors of syphilis susceptibility. These findings offered novel insights for further probing into the underlying pathogenic mechanisms of syphilis and underscored the importance of multifaceted prevention strategies against syphilis.Copyright © 2024 Elsevier Inc. All rights reserved.

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