J Psychiatry Neurosci 2012;37(1):46-52
Ke-Sheng Wang, PhD; Xuefeng Liu, PhD; Qunyuan Zhang, PhD; Nagesh Aragam, MSc; Yue Pan, MSc
Wang, Liu, Aragam, Pan — Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, Tenn.; Zhang — Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Mo.
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.
Submitted Dec. 8, 2010; Revised Mar. 5, 30, 2011; Accepted Mar. 31, 2011.
Acknowledgments: The dataset was obtained from the GAIN Data-base found at www.ncbi.nlm.nih.gov/projects/gap/ through the db-GAP accession number phs000016.v2.p2. The International Multi-Center ADHD Genetics Project (IMAGE) is a multisite, international effort supported by NIH grants R01MH081803 and R01MH62873 to Stephen V. Faraone. The genotyping of samples was provided through the Genetic Association Information Network (GAIN). Samples and associated phenotype data for the IMAGE project were provided by Dr. Faraone. We thank all the families who participated in this research.
Competing interests: None declared.
Contributors: K.-S. Wang acquired the data and designed the study. All authors contributed to the data analysis and interpretation. X. Liu and Q. Zhang offered critical guidance on the statistical analysis and contributed their statistical expertise. N. Aragam and Y. Pan performed the literature search. K.-S. Wang wrote the article, which all authors critically reviewed and approved for publication.
Correspondence to: Dr. K.-S. Wang, Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, PO Box 70259, Lamb Hall, Johnson City TN 37614-1700; email@example.com