Association of Genetic Risk for Rheumatoid Arthritis With Cognitive and Psychiatric Phenotypes Across Childhood and Adolescence

Key Points Question Is genetic liability for rheumatoid arthritis associated with cognitive and psychiatric phenotypes in children prior to the clinical onset of disease? Findings In this cohort study of 7977 children and adolescents, genetic liability for rheumatoid arthritis was associated with lower total, performance, and verbal IQ at age 8 years and symptoms of hyperactivity and inattention from ages 4 to 16 years. However, there was little evidence of association with other domains of psychopathology. Meaning These findings support a primary etiological association between genetic risk for rheumatoid arthritis and cognitive phenotypes that is not simply secondary to disease-related processes or reverse causation.
This cohort study investigates whether genomic risk for rheumatoid arthritis is associated with cognitive and psychiatric symptoms in children and adolescents.
Importance The association of rheumatoid arthritis (RA) with cognitive and psychiatric phenotypes has been recognized. However, it is not known whether these phenotypes are a consequence of disease-related factors, such as pain, or reflect shared etiological factors. Objective To investigate whether genomic risk for RA is associated with cognitive and psychiatric symptoms in children and adolescents. Design, Setting, and Participants This cohort study analyzed data from 3296 to 5936 adolescents (depending on outcome) from the Avon Longitudinal Study of Parents and Children. Clinical and questionnaire data were collected periodically from September 6, 1990, with collection ongoing, and analyzed from August 21, 2017, to May 21, 2018. Exposures Polygenic risk scores (PRSs) for RA. Main Outcomes and Measures Measures of cognition (including IQ, working memory, verbal learning, processing speed, problem solving, selective attention, and attentional control) and psychopathology (including anxiety, depression, negative symptoms, psychotic experiences, attention-deficit/hyperactivity disorder, and hyperactive and inattentive symptoms) in childhood and adolescence. Results Polygenic risk scores for RA were generated for 7977 children and adolescents (3885 [48.7%] female). Of these 7977 participants, 9 (0.11%) had a known diagnosis of RA at age 22 years. Increased PRS for RA was associated with lower total IQ (β, −0.05; 95% CI, −0.07 to −0.02; P