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

BackgroundBirth order may play a role in autoimmune diseases and early childhood infections, both factors implicated in the etiology of narcolepsy. We investigated the association between birth order and narcolepsy risk in a population-based case–control study in which all study subjects were HLA-DQB1*0602 positive.MethodsSubjects were 18–50 years old, residents of King County, Washington, and positive for HLA-DQB1*0602. Birth order was obtained from administered interviews. We used logistic regression to generate odds ratios adjusted for income and African American race.ResultsAnalyses included 67 cases (mean age 34.3 [SD = 9.1], 70.2% female) and 95 controls (mean age 35.1 [SD = 8.8], 58.1% female). Associations for birth order were as follows: first born (cases 38.8% vs. controls 50.2%, OR = 1.0; reference), second born (cases 29.9% vs. controls 32.9%, OR = 1.6; 95% CI 0.7, 3.7), and third born or higher (cases 31.3% vs. controls 16.8%, OR = 2.5; 95% CI 1.0, 6.0). A linear trend was significant (p < 0.05). Sibling number, sibling gender, having children, and number of children did not differ significantly between narcolepsy cases and controls.ConclusionsNarcolepsy risk was significantly associated with higher birth order in this population-based study of genetically susceptible individuals. This finding supports an environmental influence on narcolepsy risk through an autoimmune mechanism, early childhood infections, or both.