Parent-of-origin effects of FAS and PDLIM1 in attention-deficit/hyperactivity disorder

Abstract

Previous studies have suggested that there may be a parent-of-origin effect for attention-deficit/hyperactivity disorder(ADHD) candidate genes. The objective of the present study was to investigate parent-of-origin effects using a genome-wide association analysis of the International Multicentre ADHD Genetics (IMAGE) study sample. Family-based association analysis for ADHD using 846 ADHD probands and their parents was performed using the PLINK program, and parent-of-origin effects were studied using a Z score for the difference in paternal versus maternal odds ratios. We identified 44 single nucleotide polymorphisms (SNPs) showing parent-of-origin effects at a significance level of p < 0.001. The most significant SNP, rs7614907, is at position 3q13.33 in the CDGAP gene (p = 0.000064 for parent-of-origin effect). Furthermore, 2 genes (FAS and PDLIM1) showed moderate parent-of-origin effects (p = 0.00086 for rs9658691 and p = 0.00077 for rs11188249) and strong maternal transmission (p = 0.000059 for rs9658691 and p = 0.0000068 for rs11188249). In addition, ZNF775 showed a moderate parent-of-origin effect (p = 0.00036 for rs7790549) and strong paternal transmission (p = 0.000041 for rs7790549). We only had 1 sample available for analysis. These results suggest several genes or regions with moderate parent-of-origin effects, and these findings will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in ADHD.