Infant sibling exposure was defined as cumulative infant-years of exposure to a more youthful sibling categorized while 1 vs 1 year before 6 years of age while previously described.9 Viral studies. nuclear antigen-1 (EBNA-1) seropositivity was individually associated with an increased odds of MS/CIS in all 3 racial/ethnic organizations ( 0.001 for blacks and whites, = 0.02 for Hispanics). In contrast, CMV seropositivity was associated with a lower risk of MS/CIS in Hispanics (= 0.004) but not in blacks (= 0.95) or whites (= 0.96). Becoming born inside a low/middle-income country was associated with a lower risk of MS in Hispanics (= 0.02) but not after accounting for EBNA-1 seropositivity. Accounting for breastfeeding did not diminish the association between CMV and MS in Hispanics. Conclusions: The regularity of EBNA-1 seropositivity with MS across racial/ethnic organizations and between studies points to a strong biological link between EBV illness and MS risk. The association between past CMV illness and MS risk helps the broader hygiene hypothesis, but the inconsistency of this association across racial/ethnic groups implies noncausal associations. The hygiene hypothesis purports the modern-day rise in sensitive and autoimmune conditions is due to prevention or delay of common early-life infections. Evidence supporting a role for early-life hygiene like a risk element for multiple sclerosis (MS) includes an increased risk of MS associated with infectious mononucleosis (IM),1,C3 the medical manifestation of Epstein-Barr disease (EBV) illness delayed into adolescent or adulthood; an extremely low risk of MS in EBV antibodyCnegative individuals4,C8; and a decreased MS risk associated with higher sibling exposure early in existence9 in whites. More recently, lower rates of cytomegalovirus (CMV) illness have also been linked to improved risk of MS,10,11 albeit inconsistently.5,12 The seroprevalence and timing of infection with EBV and CMV Lycopodine vary by factors implicated in the hygiene hypothesis and by race/ethnicity. Both are ubiquitous early-life infections in developing countries.13 However, in developed countries, EBV infection and particularly CMV infection are often delayed into adolescence and adulthood. While EBV seroprevalence remains ubiquitous in adults in developed countries, CMV seropositivity ranges from 51% to 82% in US adults, depending on race/ethnicity and socioeconomic factors.14 CMV seropositivity is higher at younger ages in Hispanic and black compared to white People in america and those residing in crowded living conditions.14 CMV can be transmitted through breastmilk; consequently, declining breastfeeding rates during most of the 20th century15 could also contribute to Lycopodine declines and delays in CMV illness. In addition, serum EBV antibody titers are higher in black compared to white American youths.16 We sought to use this natural variation in seroprevalence to determine the strength and consistency of association of EBV and CMV with MS risk in blacks, Hispanics, and whites and Lycopodine to examine to what extent such associations could be explained by factors implicated Lycopodine in the hygiene hypothesis or breastfeeding. METHODS Study population. Participants in the MS Sunshine Study were recruited from your Kaiser Permanente Southern California (KPSC) regular membership between December 2011 and December 2014 via mailings and telephone. KPSC is a large health maintenance corporation with 4 million users representative of the general human population in Southern California.17 KPSC uses a electronic health record (EHR) system that includes all inpatient and outpatient encounters, diagnostic checks, diagnoses, medications, and some demographic and behavioral characteristics. Data were collected from your EHR and, after educated consent, organized in-person interview, blood draw, and self-administered questionnaire (SAQ). Standard protocol approvals, registrations, and patient consents. The study protocol was authorized by the KPSC institutional review table. Case identification. Event instances with MS or clinically isolated syndrome (CIS) were recognized with methods much like those previously explained.18,19 Briefly, we looked EHRs monthly for the 1st mention of ICD-9 diagnostic codes for MS/CIS. Diagnoses were confirmed by an MS professional (A.L.-G.) according to diagnostic criteria/consensus meanings for MS20 or CIS.21,22 Eligibility required analysis of MS or CIS within the past 1. 5 years or sign onset within the past 3 years and age 18 years. Control selection. At least 1 control participant FLN2 from your KPSC population, matched to the case on race/ethnicity, birthdate (within 2 years), sex, and KPSC facility (a surrogate measure for socioeconomic status), was recognized from your EHR and recruited. The settings were assigned the same index day as their matched case (sign onset day). Data collection. Self-identified race/ethnicity was from the interview. White colored non-Hispanics were classified as white; any black race no matter ethnicity was classified as black; and those who recognized themselves mainly because white and Hispanic were classified mainly because Hispanics. Covariates from the in-person interview included history of IM, place of birth, income, and education. Details on quantity, birthdate, and cohabitation of siblings and breastfeeding (yes/no) were from the SAQ. Age was defined as age in the index day. Infant sibling exposure was defined as cumulative infant-years of exposure to a more youthful sibling.