Fig. 5 |. Association of MS severity with educational attainment and smoking.

a, MR estimates for the effect of years of education (n = 765,283), lifetime smoking index (n = 462,690), body mass index (n = 681,275), and 25-hydroxyvitamin D (n = 441,291) on ARMSS scores; the lighter color represents nonsignificant results. b, Similarly, adjusted polygenic risk score (n = 12,584) and observational analyses of two MS cohorts (n = 2,878 and 5,228) demonstrated reduced MS severity with higher years of education in linear regression models. This effect persisted following adjustment for smoking and income. c, Mean ARMSS scores decreased with higher PGS_EDU percentile. d, Similarly, higher percentile of recorded years of education associated with lower mean ARMSS scores in the EIMS cohort. e, Mean ARMSS scores decreased with higher percentile years of education in the GEMS cohort. P values were obtained from a regression of ARMSS scores on PGS_EDU (c) or years of education (d-e), adjusted for baseline covariates. In the MR and observational analyses, point estimates (squares) reflect a 1-year increase in education, while polygenic score estimates are per standard deviation score increase. ARMSS, age-related multiple sclerosis severity score (rank-based inverse-normal transformed); IVW, inverse-variance weighted; PGS_EDU, polygenic score for years of education; RAPS, robust adjusted profile score; WM, weighted median.