International journal of women's health · 2026
Genetically Predicted IgG N-Glycosylation Traits and Risk of Pre-Eclampsia or Eclampsia: A Two-Sample and Multivariable Mendelian Randomization Study.
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Wang Shimin, Ning Haofeng, Tong Jianing, Jin Bicheng, Ye Kaijie
Аннотация
BACKGROUND: Maternal immunoglobulin G (IgG) has been implicated in placental and vascular dysfunction across pre-eclampsia and eclampsia. While clinical evidence supports the relevance of IgG-mediated immune regulation, whether specific IgG N-glycosylation traits-which critically regulate IgG concentration and effector function-are associated with the combined outcome of pre-eclampsia or eclampsia remains unclear.
METHODS: A two-sample Mendelian randomization (MR) study evaluated the causal relevance of 77 IgG N-glycosylation traits for the combined outcome of pre-eclampsia or eclampsia. Primary analysis utilized the inverse-variance weighted method, supported by robust outlier and sensitivity diagnostics. Multivariable MR (MVMR) was subsequently applied to adjust for body mass index, gestational diabetes, C-reactive protein, interleukin-6, and tumor necrosis factor-α.
RESULTS: Univariable MR identified nine IgG N-glycosylation traits nominally associated with pre-eclampsia or eclampsia: five risk-increasing (IGP6, IGP11, IGP22, IGP46, IGP51) and four risk-decreasing (IGP31, IGP48, IGP50, IGP58). Sensitivity analyses confirmed no residual heterogeneity or directional pleiotropy. In MVMR, IGP46, IGP48, and IGP58 retained nominal associations after adjustment for BMI, GDM, CRP, IL-6, and TNF-α, suggesting more stable covariate-adjusted associations among the suggestive UVMR signals. IGP46 was positively associated with pre-eclampsia or eclampsia, whereas IGP48 and IGP58 showed consistent inverse associations. Structural annotation indicated that these prioritized traits were mainly related to fucosylation and monogalactosylation of IgG glycans.
CONCLUSION: This study provides suggestive genetic evidence that specific IgG N-glycosylation traits, particularly those related to core fucosylation and monogalactosylation, may be involved in the biological architecture of pre-eclampsia or eclampsia. The findings are hypothesis-generating and require validation in pregnancy-specific glycomic cohorts and functional studies.
METHODS: A two-sample Mendelian randomization (MR) study evaluated the causal relevance of 77 IgG N-glycosylation traits for the combined outcome of pre-eclampsia or eclampsia. Primary analysis utilized the inverse-variance weighted method, supported by robust outlier and sensitivity diagnostics. Multivariable MR (MVMR) was subsequently applied to adjust for body mass index, gestational diabetes, C-reactive protein, interleukin-6, and tumor necrosis factor-α.
RESULTS: Univariable MR identified nine IgG N-glycosylation traits nominally associated with pre-eclampsia or eclampsia: five risk-increasing (IGP6, IGP11, IGP22, IGP46, IGP51) and four risk-decreasing (IGP31, IGP48, IGP50, IGP58). Sensitivity analyses confirmed no residual heterogeneity or directional pleiotropy. In MVMR, IGP46, IGP48, and IGP58 retained nominal associations after adjustment for BMI, GDM, CRP, IL-6, and TNF-α, suggesting more stable covariate-adjusted associations among the suggestive UVMR signals. IGP46 was positively associated with pre-eclampsia or eclampsia, whereas IGP48 and IGP58 showed consistent inverse associations. Structural annotation indicated that these prioritized traits were mainly related to fucosylation and monogalactosylation of IgG glycans.
CONCLUSION: This study provides suggestive genetic evidence that specific IgG N-glycosylation traits, particularly those related to core fucosylation and monogalactosylation, may be involved in the biological architecture of pre-eclampsia or eclampsia. The findings are hypothesis-generating and require validation in pregnancy-specific glycomic cohorts and functional studies.