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

• Published in: Journal of psychiatry & neuroscience Vol. 37; no. 1; pp. 46 - 52
• Main Authors: Wang, Ke-Sheng, PhD, Liu, Xuefeng, PhD, Zhang, Qunyuan, PhD, Aragam, Nagesh, MSc, Pan, Yue, MSc
• Format: Journal Article
• Language: English
• Published: Ottawa, ON Canadian Medical Association 2012; CMA Joule Inc; CMA Impact, Inc
• Subjects: Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit hyperactivity disorder; Biological and medical sciences; Child; Development and progression; Epigenetic inheritance; fas Receptor - genetics; Fathers; Fundamental and applied biological sciences. Psychology; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Humans; LIM Domain Proteins - genetics; Medical Education; Medical sciences; Microfilament Proteins - genetics; Mothers; Parents & parenting; Physiological aspects; Polymorphism, Single Nucleotide; Psychiatry; Psychoanalysis; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Research Paper; Studies; Transcription Factors; United States; Attention disorder with hyperactivity; Psychopathology; Parent; Psychiatry; Psychology
• ISSN: 1180-4882; 1488-2434
• DOI: 10.1503/jpn.100173

Background 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. Methods 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. Results 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). Limitations We only had 1 sample available for analysis. Conclusion 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.