BACKGROUND: Previous studies have demonstrated aggregation of @entity2438 traits in undiagnosed family members of @entity1 with @entity72 ( @entity72 ), which has significant implications for @entity72 risk in their offspring. This study capitalizes upon a large, quantitatively characterized clinical-epidemiologic family sample to establish the extent to which family transmission pattern and sex modulate @entity72 trait aggregation. METHODS: Data were analyzed from 5515 siblings (2657 non- @entity72 and 2858 @entity72 ) included in the Interactive @entity2438 Network. @entity2438 symptom levels were measured using the Social Responsiveness Scale (SRS) and by computing Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition ( @entity4987 ) symptom scores based on items from the SRS and Social Communication Questionnaire. Generalized estimating equation models evaluated the influence of family incidence types (single versus multiple incidence families; male-only @entity72 -affected families versus families with female @entity72 -affected @entity1 ), diagnostic group (non- @entity72 @entity1 with and without a history of @entity10791 with @entity2438 speech and @entity72 -affected @entity1 ), and sibling sex on @entity72 symptom levels. RESULTS: Non- @entity72 @entity1 manifested elevated @entity72 symptom burden when they were members of multiple incidence families-this effect was accentuated for male @entity1 in female @entity72 -containing families-or when they had a history of @entity10791 with @entity2438 qualities of speech. In this sample, @entity72 -affected @entity1 from multiple incidence families had lower symptom levels than their counterparts in single incidence families. Recurrence risk for @entity72 was higher for @entity1 from female @entity72 -containing families than for @entity1 from male-only families. CONCLUSIONS: Sex and patterns of family transmission modulate the risk of @entity2438 symptom burden in undiagnosed siblings of @entity72 -affected @entity1 . Identification of these symptoms/traits and their molecular genetic causes may have significant implications for genetic counseling and for understanding inherited liabilities that confer risk for @entity72 in successive generations. @entity2438 symptom elevations were more dramatic in non- @entity72 @entity1 from multiple incidence families and those with a history of @entity10791 and @entity2438 qualities of speech, identifying sub-groups at substantially greater transmission risk. Higher symptom burden and greater recurrence in @entity1 from female @entity72 -containing families indicate that @entity1423 patterns are further qualified by sex-specific thresholds, supportive of the notion that females require a higher burden of deleterious liability to cross into categorical @entity72 diagnosis.

Quantitative XXXX symptom patterns recapitulate differential mechanisms of genetic transmission in single and multiple incidence families.

@entity1 :: ('9606', 'Species') :: ['children'] @entity1423 :: ('MESH:D001791', 'Disease') :: ['familial aggregation'] @entity4987 :: ('1398', 'Species') :: ['DSM-5'] @entity2438 :: ('MESH:D001321', 'Disease') :: ['autism', 'autistic', 'Autism'] @entity72 :: ('MESH:D002659', 'Disease') :: ['ASD', 'autism spectrum disorder'] @entity10791 :: ('MESH:D007805', 'Disease') :: ['language delay']
@entity2438 :: (MESH:D001321,Disease) :: ['autism']
