title: A genome-wide survey of transgenerational genetic effects in autism.
abstract: Effects of parental genotype or parent-offspring genetic interaction are well established in model organisms for a variety of traits. However, these transgenerational genetic models are rarely studied in humans. We have utilized an autism case-control study with 735 mother-child pairs to perform genome-wide screening for maternal genetic effects and maternal-offspring genetic interaction. We used simple models of single locus parent-child interaction and identified suggestive results (P<10(-4)) that cannot be explained by main effects, but no genome-wide significant signals. Some of these maternal and maternal-child associations were in or adjacent to autism candidate genes including: PCDH9, FOXP1, GABRB3, NRXN1, RELN, MACROD2, FHIT, RORA, CNTN4, CNTNAP2, FAM135B, LAMA1, NFIA, NLGN4X, RAPGEF4, and SDK1. We attempted validation of potential autism association under maternal-specific models using maternal-paternal comparison in family-based GWAS datasets. Our results suggest that further study of parental genetic effects and parent-child interaction in autism is warranted.
authors.affiliation: Department of Psychiatry and Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Tsang
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Croen
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Torres
authors.forename: Martin
authors.initials: M
authors.lastname: Kharrazi
authors.forename: Gerald N
authors.initials: GN
authors.lastname: Delorenze
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Windham
authors.forename: Cathleen K
authors.initials: CK
authors.lastname: Yoshida
authors.forename: Ousseny
authors.initials: O
authors.lastname: Zerbo
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Weiss
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D030541:Databases, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D009034:Mother-Child Relations; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000091042:Reelin Protein