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While previous studies have demonstrated an association between individual factors related to lifestyle and the risk of systemic lupus erythematosus (SLE), it is unclear how the combination of these factors might affect the risk of incident SLE. This study was undertaken to prospectively evaluate whether a combination of healthy lifestyle factors is associated with a lower risk of incident SLE and its subtypes (anti-double-stranded DNA [anti-dsDNA]-positive and anti-dsDNA-negative SLE).The study included 185,962 women from the Nurses' Health Study (NHS) and NHSII cohorts, among whom there were 203 incident cases of SLE (96 with anti-dsDNA-positive SLE, 107 with anti-dsDNA-negative SLE) during 4,649,477 person-years of follow-up. The Healthy Lifestyle Index Score (HLIS) was calculated at baseline and approximately every 2 years during follow-up, with scores assigned for 5 healthy lifestyle factors: alcohol consumption, body mass index, smoking, diet, and exercise. A time-varying Cox proportional hazards regression model was used to estimate the adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the risk of SLE. In addition, the percentage of partial population attributable risk (PAR%) of SLE development was calculated.A higher HLIS was associated with a lower risk of SLE overall (HR 0.81 [95% CI 0.71-0.94]) and a lower risk of anti-dsDNA-positive SLE (HR 0.78 [95% CI 0.63-0.95]). Women with ≥4 healthy lifestyle factors had the lowest risk of SLE overall (HR 0.42, 95% CI 0.25-0.70) and lowest risk of anti-dsDNA-positive SLE (HR 0.35, 95% CI 0.17-0.75) as compared to women with only 1 healthy behavior or no healthy behaviors. The PAR% of SLE development was 47.7% (95% CI 23.1-66.6%), assuming that the entire population had adhered to at least 4 healthy lifestyle behaviors.These results indicate that the risk of developing SLE, a disease in which significant evidence of genetic involvement has been established, might be reduced by nearly 50% with adherence to modifiable healthy lifestyle behaviors.

Objective To elucidate how postdiagnosis multimorbidity and lifestyle changes contribute to the excess mortality of rheumatoid arthritis (RA). Methods We performed a matched cohort study among women in the Nurses' Health Study (1976-2018). We identified women with incident RA and matched each by age and year to 10 non-RA comparators at the RA diagnosis index date. Specific causes of death were ascertained via death certificates and medical record review. Lifestyle and morbidity factors were reported biennially; 61 chronic conditions were combined into the Multimorbidity Weighted Index (MWI). After adjusting for baseline confounders, we used inverse probability weighting analysis to examine the mediating influence of postindex MWI scores and lifestyle factors on total, cardiovascular, and respiratory mortality, comparing women with RA to their matched comparators. Results We identified 1,007 patients with incident RA and matched them to 10,070 non-RA comparators. After adjusting for preindex confounders, we found that hazard ratios (HRs) and 95% confidence intervals (95% CIs) were higher for total mortality (HR 1.46 [95% CI 1.32, 1.62]), as well as cardiovascular (HR 1.54 [95% CI 1.22, 1.94]) and respiratory (HR 2.75 [95% CI 2.05, 3.71]) mortality in patients with RA compared to non-RA comparators. Adjusting for postindex lifestyle factors (physical activity, body mass index, diet, smoking) attenuated but did not substantially account for this excess RA mortality. After additional adjustment for postindex MWI scores, patients with RA had HRs of 1.18 (95% CI 1.05, 1.32) for total, 1.19 (95% CI 0.94, 1.51) for cardiovascular, and 1.93 (95% CI 1.42, 2.62) for respiratory mortality. Conclusion We found that MWI scores substantially accounted for the excess total and cardiovascular mortality among women with RA. This finding underscores the importance of monitoring for the total disease burden as a whole in monitoring patients with RA.

Background Prior studies suggest that fish may be protective for rheumatoid arthritis (RA) risk perhaps through the anti-inflammatory effect of omega-3 fatty acid, but this relationship has not been clearly established. Therefore, we investigated fish intake and RA risk by serologic status, age of onset, and smoking using a prospective cohort study with large sample size, repeated measures of dietary intake, and lengthy follow-up. Methods We studied fish intake and RA risk among 166,013 women in two prospective cohorts, the Nurses’ Health Study (NHS, 1984–2014) and NHSII (1991–2015). Fish intake was assessed using food frequency questionnaires at baseline and every 4 years. Incident RA during follow-up and serologic status were determined by medical record review. Pooled Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for RA (overall and by serologic status and age at diagnosis) for fish intake frequency. We tested for a smoking-fish interaction for RA risk. Results During 3,863,909 person-years of follow-up, we identified 1080 incident RA cases. Increasing fish intake was not associated with all RA (≥4 servings/week: multivariable HR 0.93 [95%CI 0.67–1.28] vs. 55 years old (p for trend = 0.037). Among women ≤55 years old, frequent fish intake (vs. infrequent) had HRs (95%CIs) of: 0.73 (0.52–1.02) for all RA, 0.85 (0.55–1.32) for seropositive RA, and 0.55 (0.32–0.94) for seronegative RA. Ever smokers with infrequent fish intake had highly elevated risk for RA onset ≤55 years (HR 2.59, 95%CI 1.65–4.06), while ever smokers with frequent fish intake had modestly elevated RA risk (HR 1.29, 95%CI 1.07–1.57; vs. never smokers/frequent fish intake; p for smoking-fish interaction = 0.039). Conclusion In this large prospective cohort study, we found no clear protective effect of fish or marine omega-3 fatty acid intake on RA risk, overall or by serologic status. We found that fish intake attenuated the strong association of smoking for RA diagnosed ≤55 years of age, but this requires further study.

IMPORTANCE: It has long been hypothesized that depression may increase the risk of developing autoimmune disease; however, rigorous empirical evidence is sparse. OBJECTIVE: To evaluate whether an association exists between depression and risk of incident systemic lupus erythematosus (SLE), a paradigmatic, systemic autoimmune disease. DESIGN, SETTING, AND PARTICIPANTS: This 20-year prospective, longitudinal cohort study evaluated data collected from 2 cohorts of women participating in the Nurses’ Health Study (1996-2012) and the Nurses’ Health Study II (1993-2013). Data analyses were conducted from August 2017 to May 2018. MAIN OUTCOMES AND MEASURES: Incident SLE with 4 or more American College of Rheumatology criteria was ascertained by self-report and confirmed by medical record review. Depression was assessed repeatedly throughout follow-up according to whether women reported having received a clinician’s diagnosis of depression, regular antidepressant use, or a score of less than 60 on the 5-item Mental Health Inventory (MHI-5). Whether longitudinally assessed health risk factors (eg, cigarette smoking, body mass index, oral contraceptive use, menopause or postmenopausal hormone use, alcohol use, exercise, or diet) accounted for increased SLE risk among women with vs without depression was examined. Cox proportional hazards regression models were used to estimate risk of SLE. In addition, the association of depression lagged by 4 years, and depression status at baseline with incident SLE throughout follow-up was assessed. RESULTS: Data from 194 483 women (28-93 years of age; 93% white) were included. During 20 years of follow-up, 145 cases of SLE occurred. Compared with women with no depression, women with a history of depression had a subsequent increased risk of SLE (HR, 2.67; 95% CI, 1.91-3.75; P

OBJECTIVE: To investigate whether a dietary pattern derived using inflammatory biomarkers is associated with rheumatoid arthritis (RA) risk. METHODS: We prospectively followed 79,988 women in the Nurses’ Health Study (NHS, 1984–2014) and 93,572 women in the NHSII (1991–2013); incident RA was confirmed by medical records. Food frequency questionnaires (FFQ) were completed at baseline and approximately every 4 years. Inflammatory dietary pattern was assessed from FFQ data using the Empirical Dietary Inflammatory Pattern (EDIP), including 18 anti-/pro-inflammatory food/beverage groups weighted by correlations with plasma inflammatory biomarkers (interleukin-6, C-reactive protein, and tumor necrosis factor-α receptor 2). We investigated associations between EDIP and RA using Cox regression. RESULTS: We identified 1,185 incident RA cases over 4,425,434 person-years. EDIP was not associated with overall RA risk (p trend=0.21 across EDIP quartiles). Among women ≤55 years, increasing EDIP was associated with increased overall RA risk; HRs (95%CIs) across EDIP quartiles were: 1.00 (reference), 1.14 (0.86–1.51), 1.35 (1.03–1.77), and 1.38 (1.05–1.83; p for trend=0.01). Adjusting for BMI attenuated this association. Increasing EDIP was associated with increased seropositive RA risk among women ≤55 years (p for trend=0.04). There was no association between EDIP and RA among women >55 years (EDIP-age interaction: p=0.03). CONCLUSION: An inflammatory dietary pattern was associated with increased seropositive RA risk with onset ≤55 years old, and this association may be partially mediated through BMI.

ObjectivesSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, subtyped according to clinical manifestations and autoantibodies. Evidence concerning cigarette smoking and SLE risk has been conflicting. We investigated smoking and SLE risk, overall and by anti-double stranded DNA (dsDNA) presence, in two prospective cohort studies.MethodsThe Nurses’ Health Study (NHS) enrolled 121 701 US female nurses in 1976; Nurses’ Health Study II (NHSII) enrolled 116 430 in 1989. Lifestyle, environmental and medical data were collected through biennial questionnaires. Incident SLE was confirmed by medical record review. Cox regression models estimated HRs of SLE, overall and by dsDNA subtype, in association with time-varying smoking status and cumulative smoking pack-years through the 2-year cycle prior to diagnosis, controlling for potential confounders.ResultsAmong 286 SLE cases identified (159 in NHS (1978–2012) and 127 in NHSII (1991–2013)), mean age was 49.2 (10.3) years and 42% were dsDNA+ at SLE diagnosis. At baseline, 45% of women had ever smoked, 51% of whom currently smoked. Compared with never smokers, current smokers had increased dsDNA+ SLE risk (HR 1.86 (1.14–3.04)), whereas past smokers did not (HR 1.31 (0.85–2.00)). Women who smoked >10 pack-years (vs never) had an elevated dsDNA+ SLE risk (HR 1.60(95% CI 1.04 to 2.45)) compared with never smokers. No associations were observed between smoking status or pack-years and overall SLE or dsDNA− SLE.ConclusionStrong and specific associations of current smoking and >10 pack-years of smoking with dsDNA+ SLE were observed. This novel finding suggests smoking is involved in dsDNA+ SLE pathogenesis.

Objective. The aim of this study was to examine the relationship between preclinical circulating 25-hydroxyvitamin D [25(OH)D] and RA in two nested case–control studies within the prospective cohort Nurses’ Health Study (NHS) and NHS II (NHSII). Methods. We included 166 women with RA and blood specimens collected 3 months to 16 years prior to the first RA symptom and 490 matched controls (3:1, matched on age, date of blood draw, hormonal factors). We calculated the odds ratio (OR) and 95% CI for incident RA using conditional logistic regression multivariable adjusted models, including additional covariates for smoking status, parity and breastfeeding, alcohol consumption, BMI, median income and region of residence in the USA. We repeated analyses stratified by time from blood draw to RA diagnosis (3 months to

To assess biobank participants' preferences for disclosure of genetic research results.We conducted a cross-sectional survey of participants in the OurGenes, OurHealth, OurCommunity biobank. Respondents were surveyed about preferences for disclosure, importance of disclosure, communication of results with practitioners, and sharing of results after respondents' death. Multivariate regression analysis was used to assess independent sociodemographic and clinical predictors of disclosure preferences. Data collection occurred from June 6, 2011, to June 25, 2012.Among 1154 biobank participants, 555 (48%) responded. Most thought that research result disclosure was important (90%). Preference for disclosure varied, depending on availability of disease treatment (90% vs 64%, P.001), high vs low disease risk (79% vs 66%, P.001), and serious vs mild disease (83% vs 68%, P.001). More than half of respondents (57%) preferred disclosure even when there is uncertainty about the results' meaning, and 87% preferred disclosure if the disease is highly heritable. Older age was positively associated with interest in disclosure, whereas female sex, nonwhite race, diabetes mellitus, and depression and/or anxiety were negatively associated with disclosure. More than half of respondents (52%) would want their results returned to their nearest biological relative after death.OurGenes biobank participants report strong preferences for disclosure of research results, and most would designate a relative to receive results after death. Participant preferences for serious vs mild disease, high vs low disease risk, and availability of disease treatment differed significantly. Future research should consider family members' preferences for receiving research results from enrolled research participants.