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

Birth 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.

Subjects 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.

Analyses 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.

Narcolepsy 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.