Increased female autosomal burden of rare copy number variants in human populations and in autism families.

TitleIncreased female autosomal burden of rare copy number variants in human populations and in autism families.
Publication TypeJournal Article
Year of Publication2015
AuthorsDesachy G, Croen LA, Torres AR, Kharrazi M, Delorenze GN, Windham GC, Yoshida CK, Weiss LA
JournalMolecular psychiatry
Volume20
Pagination170-5
Date Published2
ISSN1476-5578
AbstractAutosomal genetic variation is presumed equivalent in males and females and makes a major contribution to disease risk. We set out to identify whether maternal copy number variants (CNVs) contribute to autism spectrum disorders (ASDs). Surprisingly, we observed a higher autosomal burden of large, rare CNVs in females in the population, reflected in, but not unique to, ASD families. Meta-analysis across control data sets confirms female excess in CNV number (P=2.1 × 10(-5)) and gene content (P=4.1 × 10(-3)). We additionally observed CNV enrichment in ASD mothers compared with control mothers (P=0.03). We speculate that tolerance for CNV burden contributes to decreased female fetal loss in the population and that ASD-specific maternal CNV burden may contribute to high sibling recurrence. These data emphasize the need for study of familial CNV risk factors in ASDs and the requirement of sex-matched comparisons.
DOI10.1038/mp.2014.179