Traits of ADHD and autism in girls with a twin brother: a Mendelian randomization study.
It has been hypothesized that prenatal exposure to testosterone may be associated with traits of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). We conducted a population-based study of dizygotic female twins to elucidate this hypothesis, assuming that the sex of the co-twin influences the level of prenatal exposure to testosterone. We invited parents of 24,552 3- to 15-year-old twins to answer questionnaires on traits of ADHD and ASD. We analysed the data using a proportional odds model with sex of the co-twin as an instrumental variable for prenatal exposure to testosterone of female twins. We received responses for 6,339 girls from dizygotic twin pairs. Odds ratios for male versus female co-twin were 0.71 (95 % confidence interval 0.61-0.81) for ADHD traits and 0.74 (0.66-0.83) for ASD traits, indicating that a twin brother reduces traits of ADHD and ASD in females. In conclusion, we found that female twins with a twin brother scored significantly lower in parent-reported traits of ADHD and ASD than those with a twin sister. The reason for this may be parental reporting bias, or confounding by unmeasured variables, or a causal effect of an intrauterine environment modified by the sex of the co-twin in the opposite direction of what we expected.
Department of Epidemiology, School of Public Health, Aarhus University, Aarhus C, Aarhus, Denmark. ja@soci.au.dk
Jørn
J
Attermann
Carsten
C
Obel
Niels
N
Bilenberg
Claudia Maria
CM
Nordenbæk
Axel
A
Skytthe
Jørn
J
Olsen
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000235:genetics; D001321:Autistic Disorder / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003718:Denmark; D004200:Diseases in Twins / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D010290:Parents; D010641:Phenotype; D012042:Registries