Dataset Information

Association of pregnancies with risk of multiple sclerosis.

ABSTRACT:

Background

Pregnancies have an impact on the disease course of multiple sclerosis (MS), but their relationship with MS risk is yet unclear.

Objective

To determine the relationships of pregnancies and gynecological diagnoses with MS risk.

Methods

In this retrospective case-control study, we assessed differences in gynecological International Classification of Diseases, 10th Revision (ICD-10) code recording rates between women with MS (n = 5720), Crohn's disease (n = 6280), or psoriasis (n = 40,555) and women without these autoimmune diseases (n = 26,729) in the 5 years before diagnosis.

Results

Twenty-eight ICD-10 codes were recorded less frequently for women with MS as compared to women without autoimmune disease, 18 of which are pregnancy-related. After adjustment for pregnancies, all codes unrelated to pregnancies were still negatively associated with MS. In a sensitivity analysis excluding women with evidence for possible demyelinating events before diagnosis, all associations were more pronounced. In comparison to women with psoriasis, most associations could be confirmed; that was not true in comparison to women with Crohn's disease.

Conclusion

Our findings provide evidence for a possible protective effect of pregnancies on MS risk likely independent of or in addition to a previously suggested reversed causality. The negative associations of gynecological disorders with disease risk need further investigation. The associations might be shared by different autoimmune diseases.

SUBMITTER: Gasperi C

PROVIDER: S-EPMC9315178 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Association of pregnancies with risk of multiple sclerosis.

Gasperi Christiane C Hapfelmeier Alexander A Schneider Antonius A Kuhn Klaus A KA Donnachie Ewan E Hemmer Bernhard B

Multiple sclerosis (Houndmills, Basingstoke, England) 20220318 10

<h4>Background</h4>Pregnancies have an impact on the disease course of multiple sclerosis (MS), but their relationship with MS risk is yet unclear.<h4>Objective</h4>To determine the relationships of pregnancies and gynecological diagnoses with MS risk.<h4>Methods</h4>In this retrospective case-control study, we assessed differences in gynecological International Classification of Diseases, 10th Revision (ICD-10) code recording rates between women with MS (<i>n</i> = 5720), Crohn's disease (<i>n< ...[more]

PMID: 35301890

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Project description:Polygenic inheritance plays a pivotal role in driving multiple sclerosis susceptibility, an inflammatory demyelinating disease of the CNS. We developed polygenic risk scores (PRS) of multiple sclerosis and assessed associations with both disease status and severity in cohorts of European descent. The largest genome-wide association dataset for multiple sclerosis to date (n = 41 505) was leveraged to generate PRS scores, serving as an informative susceptibility marker, tested in two independent datasets, UK Biobank [area under the curve (AUC) = 0.73, 95% confidence interval (CI): 0.72-0.74, P = 6.41 × 10-146] and Kaiser Permanente in Northern California (KPNC, AUC = 0.8, 95% CI: 0.76-0.82, P = 1.5 × 10-53). Individuals within the top 10% of PRS were at higher than 5-fold increased risk in UK Biobank (95% CI: 4.7-6, P = 2.8 × 10-45) and 15-fold higher risk in KPNC (95% CI: 10.4-24, P = 3.7 × 10-11), relative to the median decile. The cumulative absolute risk of developing multiple sclerosis from age 20 onwards was significantly higher in genetically predisposed individuals according to PRS. Furthermore, inclusion of PRS in clinical risk models increased the risk discrimination by 13% to 26% over models based only on conventional risk factors in UK Biobank and KPNC, respectively. Stratifying disease risk by gene sets representative of curated cellular signalling cascades, nominated promising genetic candidate programmes for functional characterization. These pathways include inflammatory signalling mediation, response to viral infection, oxidative damage, RNA polymerase transcription, and epigenetic regulation of gene expression to be among significant contributors to multiple sclerosis susceptibility. This study also indicates that PRS is a useful measure for estimating susceptibility within related individuals in multicase families. We show a significant association of genetic predisposition with thalamic atrophy within 10 years of disease progression in the UCSF-EPIC cohort (P < 0.001), consistent with a partial overlap between the genetics of susceptibility and end-organ tissue injury. Mendelian randomization analysis suggested an effect of multiple sclerosis susceptibility on thalamic volume, which was further indicated to be through horizontal pleiotropy rather than a causal effect. In summary, this study indicates important, replicable associations of PRS with enhanced risk assessment and radiographic outcomes of tissue injury, potentially informing targeted screening and prevention strategies.

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Dataset Information

Association of pregnancies with risk of multiple sclerosis.

Background

Objective

Methods

Results

Conclusion

Publications

Association of pregnancies with risk of multiple sclerosis.

Similar Datasets

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