Pregnancy does not modify the risk of MS in genetically susceptible women

Cameron J Adams; Sean L Wu; Xiaorong Shao; Patrick T Bradshaw; Edlin Gonzales; Jessica B Smith; Anny H Xiang; Kalliope H Bellesis; Terrence Chinn; Steffan D Bos; Marte Wendel-Haga; Tomas Olsson; Ingrid Kockum; Annette M Langer-Gould; Catherine Schaefer; Lars Alfredsson; Lisa F Barcellos

doi:10.1212/NXI.0000000000000898

Pregnancy does not modify the risk of MS in genetically susceptible women

Neurol Neuroimmunol Neuroinflamm. 2020 Oct 9;7(6):e898. doi: 10.1212/NXI.0000000000000898. Print 2020 Nov.

Authors

Cameron J Adams¹, Sean L Wu², Xiaorong Shao², Patrick T Bradshaw², Edlin Gonzales², Jessica B Smith², Anny H Xiang², Kalliope H Bellesis², Terrence Chinn², Steffan D Bos², Marte Wendel-Haga², Tomas Olsson², Ingrid Kockum², Annette M Langer-Gould², Catherine Schaefer², Lars Alfredsson², Lisa F Barcellos²

Affiliations

¹ From the Divisions of Epidemiology and Biostatistics (C.J.A., S.L.W.), School of Public Health, University of California, Berkeley, Berkeley, CA; Genetic Epidemiology and Genomics Laboratory (X.S., L.F.B.), University of California, Berkeley, Berkeley, CA; School of Public Health (P.T.B.), University of California, Berkeley, Berkeley, CA, USA; Department of Research & Evaluation (E.G., J.B.S., A.H.X.), Kaiser Permanente Southern California, Los Angeles, CA; Kaiser Permanente Division of Research (K.H.B., T.C., C.S.), Kaiser Permanente Northern California, Oakland, CA; University of Oslo (S.D.B.), Institute of Clinical Medicine & Oslo University Hospital, Department of Neurology, Oslo, Norway; Oslo University Hospital (M.W.-H.), Department of Neurology, Oslo, Norway; Department of Clinical Neuroscience (T.O.), Karolinska Instituet, Stockholm, Sweden; Department of Clinical Neuroscience (I.K.), Karolinska Institutet, Stockholm, Sweden; Southern California Permanente Medical Group/Kaiser Permanente (A.M.L.-G.), Department of Neurology, Los Angeles, CA; and Institute of Environmental Medicine (L.A.), Karolinska Institutet and Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden. cam.adams@berkeley.edu.
² From the Divisions of Epidemiology and Biostatistics (C.J.A., S.L.W.), School of Public Health, University of California, Berkeley, Berkeley, CA; Genetic Epidemiology and Genomics Laboratory (X.S., L.F.B.), University of California, Berkeley, Berkeley, CA; School of Public Health (P.T.B.), University of California, Berkeley, Berkeley, CA, USA; Department of Research & Evaluation (E.G., J.B.S., A.H.X.), Kaiser Permanente Southern California, Los Angeles, CA; Kaiser Permanente Division of Research (K.H.B., T.C., C.S.), Kaiser Permanente Northern California, Oakland, CA; University of Oslo (S.D.B.), Institute of Clinical Medicine & Oslo University Hospital, Department of Neurology, Oslo, Norway; Oslo University Hospital (M.W.-H.), Department of Neurology, Oslo, Norway; Department of Clinical Neuroscience (T.O.), Karolinska Instituet, Stockholm, Sweden; Department of Clinical Neuroscience (I.K.), Karolinska Institutet, Stockholm, Sweden; Southern California Permanente Medical Group/Kaiser Permanente (A.M.L.-G.), Department of Neurology, Los Angeles, CA; and Institute of Environmental Medicine (L.A.), Karolinska Institutet and Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden.

Abstract

Objective: To use the case-only gene-environment (G [Formula: see text] E) interaction study design to estimate interaction between pregnancy before onset of MS symptoms and established genetic risk factors for MS among White adult females.

Methods: We studied 2,497 female MS cases from 4 cohorts in the United States, Sweden, and Norway with clinical, reproductive, and genetic data. Pregnancy exposure was defined in 2 ways: (1) [Formula: see text] live birth pregnancy before onset of MS symptoms and (2) parity before onset of MS symptoms. We estimated interaction between pregnancy exposure and established genetic risk variants, including a weighted genetic risk score and both HLA and non-HLA variants, using logistic regression and proportional odds regression within each cohort. Within-cohort associations were combined using inverse variance meta-analyses with random effects. The case-only G × E independence assumption was tested in 7,067 individuals without MS.

Results: Evidence for interaction between pregnancy exposure and established genetic risk variants, including the strongly associated HLA-DRB1*15:01 allele and a weighted genetic risk score, was not observed. Results from sensitivity analyses were consistent with observed results.

Conclusion: Our findings indicate that pregnancy before symptom onset does not modify the risk of MS in genetically susceptible White females.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Age of Onset
Female
Gene-Environment Interaction*
Genetic Predisposition to Disease / genetics*
Humans
Middle Aged
Multiple Sclerosis / epidemiology
Multiple Sclerosis / etiology*
Multiple Sclerosis / genetics
Norway / epidemiology
Pregnancy*
Registries*
Reproductive History*
Risk
Sweden / epidemiology
United States / epidemiology
White People / ethnology
White People / genetics
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding