Active and Passive Smoking and Risk of Narcolepsy in People with HLA DQB1*0602: A Population-Based Case-Control Study

Abstract

Background: We examined the risk of narcolepsy associated with active and passive smoking among genetically susceptible individuals. Methods: We conducted a popula- tion-based case-control study in King County, Wash., USA. Between 2001 and 2005, we enrolled 67 cases through physicians and public outreach, and 95 controls through random-digit dialing. Subjects were aged between 18 and 50 years and positive for HLA DQB1*0602. All subjects were administered in-person interviews about their history of active and passive smoking. Results: We observed an increased risk of narcolepsy associated with having lived with two or more household smokers (odds ratio, OR = 5.1; 95% confidence interval, CI: 1.6, 12.1); with a grandparent or a sibling who smoked (OR = 3.0; 95% CI: 1.1, 8.3); with a non-family household member who smoked (OR = 3.7; 95% CI: 1.6, 8.6); and with an unrelated smoker for 1–2 years (OR = 3.1; 95% CI: 1.0, 9.0). The risk of narcolepsy was not associated with exposure to smoke at work or with active smoking before age 21 or before age of narcolepsy onset. Conclusion: Passive smoking may be a risk factor for narcolepsy in subjects with HLA DQB1*0602. Future studies could help clarify whether passive smoking is an important etiologic component of narcolepsy among genetically susceptible individuals.

mice: Multivariate Imputation by Chained Equations inR

“…Applications of imputation by chained equations have now appeared in quite diverse fields: addiction (Schnoll et al 2006;MacLeod et al 2008;Adamczyk and Palmer 2008;Caria et al 2009;Morgenstern et al 2009), arthritis and rheumatology (Wolfe et al 2006;Rahman et al 2008;van den Hout et al 2009), atherosclerosis (Tiemeier et al 2004;van Oijen et al 2007;McClelland et al 2008), cardiovascular system (Ambler et al 2005;van Buuren et al 2006a;Chase et al 2008;Byrne et al 2009;Klein et al 2009), cancer (Clark et al 2001Royston et al 2004;Barosi et al 2007;Fernandes et al 2008;Sharma et al 2008;McCaul et al 2008;Huo et al 2008;Gerestein et al 2009), epidemiology (Cummings et al 2006;Hindorff et al 2008;Mueller et al 2008;Ton et al 2009), endocrinology (Rouxel et al 2004;Prompers et al 2008), infectious diseases (Cottrell et al 2005;Walker et al 2006;Cottrell et al 2007;Kekitiinwa et al 2008;Nash et al 2008;Sabin et al 2008;Thein et al 2008;Garabed et al 2008;Michel et al 2009), genetics …”

Birth order and narcolepsy risk among genetically susceptible individuals: A population-based case–control study

“…Controls were 18-50 year old residents of King County identified through random digit dialing. Potential controls within households were sampled using the randomized recruitment method in which age and gender-specific sampling fractions were applied to create a distribution of controls similar to that of the projected distribution of cases [7,9]. All study procedures were reviewed and approved by the University of Washington Institutional Review Board.…”

“…For linear trend of birth order on narcolepsy prevalence, we used a score test for trend. For multivariable models, we used unconditional logistic regression to obtain estimated odds ratios (ORs) and 95 percent confidence intervals (CIs), adapted to account for the sampling mechanism for controls [16], as described elsewhere [7]. Because household income was missing for five cases and seven controls, we multiplied imputed household income using age, African American race, interview year, and case status as predictors, as detailed previously [7,9].…”

“…Genetically, narcolepsy has strong associations with HLA-DQB1*0602 [5] and polymorphisms in the T-cell receptor alpha locus [6]. Environmentally, narcolepsy has been associated with passive smoking [7], streptococcal infection [8,9], and season of birth [10]. The combination of these, and likely other factors, is thought to initiate an immune response resulting in selective loss of hypocretin-producing cell in the dorsolateral hypothalamus and reduced cerebrospinal hypocretin levels [11].…”

Antistreptococcal Antibodies Found in Patients with Narcolepsy

“…However, findings may be coincidental and are likely confounded by bias recall. Increased smoking exposure in patients with narcolepsy suggests the effect is secondary to increased upper respiratory tract infections in secondary smoking [2]. More than 20 years ago, increased antistreptolysin O (ASO) and anti-DNAse B (ADB) titers were reported in a small number of patients with narcolepsy.…”