title: Increased female autosomal burden of rare copy number variants in human populations and in autism families.
abstract: Autosomal 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.
authors.affiliation: Department of Psychiatry and Institute for Human Genetics, UCSF, San Francisco, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Desachy
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Croen
authors.affiliation: Center for Persons with Disabilities, Utah State University, Logan, UT, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Torres
authors.affiliation: Genetic Disease Screening Program, California Department of Public Health, Richmond, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kharrazi
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: G N
authors.initials: GN
authors.lastname: Delorenze
authors.affiliation: Division of Environmental and Occupational Disease Control, California Department of Public Health, Richmond, CA, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Windham
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Yoshida
authors.affiliation: Department of Psychiatry and Institute for Human Genetics, UCSF, San Francisco, CA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Weiss
mesh_terms: D000067877:Autism Spectrum Disorder / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D056915:DNA Copy Number Variations / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015201:Meta-Analysis as Topic; D009034:Mother-Child Relations; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D012307:Risk Factors