Examining and interpreting the female protective effect against autistic behavior

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 13; pp. 5258 - 5262
• Main Authors: Robinson, Elise B., Lichtenstein, Paul, Anckarsäter, Henrik, Happé, Francesca, Ronald, Angelica
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences 26.03.2013; National Acad Sciences
• Series: From the Cover
• Subjects: Adolescent; adolescents; Autism; Autistic disorder; Autistic Disorder - genetics; Basic Medicine; Biological and medical sciences; Biological Sciences; Child clinical studies; children; Developmental disorders; early development; epidemiology; Etiology; family studies; Female; Females; Gender differences; genes; Genetics; girls; Humans; Infantile autism; Male; males; Medical genetics; Medical sciences; Medicinska och farmaceutiska grundvetenskaper; Neurology; Pathology; Personality traits; Pervasive child development disorders; phenotype; Phenotypic traits; protective effect; Protective effects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Quantitative Trait, Heritable; risk; Sex Characteristics; Siblings; Sweden; Twin studies; Twins; Twins, Dizygotic; Twins, Monozygotic; Sweden; Human; genetic; Family study; Dizygotic twin; Sex; family studies; Protective factor; Male; Developmental disorder; Epidemiology; Autism; Female; Public health
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1211070110

Male preponderance in autistic behavioral impairment has been explained in terms of a hypothetical protective effect of female sex, yet little research has tested this hypothesis empirically. If females are protected, they should require greater etiologic load to manifest the same degree of impairment as males. The objective of this analysis was to examine whether greater familial etiologic load was associated with quantitative autistic impairments in females compared with males. Subjects included 3,842 dizygotic twin pairs from the Twins Early Development Study (TEDS) and 6,040 dizygotic twin pairs from the Child and Adolescent Twin Study of Sweden (CATSS). In both samples, we compared sibling autistic traits between female and male probands, who were identified as children scoring in the top 90th and 95th percentiles of the population autistic trait distributions. In both TEDS and CATSS, siblings of female probands above the 90th percentile had significantly more autistic impairments than the siblings of male probands above the 90th percentile. The siblings of female probands above the 90th percentile also had greater categorical recurrence risk in both TEDS and CATSS. Results were similar in probands above the 95th percentile. This finding, replicated across two nationally-representative samples, suggests that female sex protects girls from autistic impairments and that girls may require greater familial etiologic load to manifest the phenotype. It provides empirical support for the hypothesis of a female protective effect against autistic behavior and can be used to inform and interpret future gene finding efforts in autism spectrum disorders.