Department of Psychiatry and Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
Authors
Croen LA, Delorenze GN, Kharrazi M, Torres AR, Tsang KM, Weiss LA, Windham GC, Yoshida CK, Zerbo O
Tsang KM, Croen LA, Torres AR, Kharrazi M, Delorenze GN, Windham GC, Yoshida CK, Zerbo O, Weiss LA. A genome-wide survey of transgenerational genetic effects in autism. PLoS One 2013 Oct 24;8(10):e76978. doi: 10.1371/journal.pone.0076978. eCollection 2013.
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.