AUTHOR=Ma Suk-Ling , Chen Lu Hua , Lee Chi-Chiu , Lai Kelly Y. C. , Hung Se-Fong , Tang Chun-Pan , Ho Ting-Pong , Shea Caroline , Mo Flora , Mak Timothy S. H. , Sham Pak-Chung , Leung Patrick W. L. 

TITLE=Genetic Overlap Between Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in SHANK2 Gene

JOURNAL=Frontiers in Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.649588

DOI=10.3389/fnins.2021.649588

ISSN=1662-453X

ABSTRACT=<p><bold>Background:</bold> Recent findings indicated a high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), as well as shared genetic influences on them. The latter might contribute at least partly to the former clinical scenario. This study aimed at investigating whether <italic>SHANK</italic> genes were potential pleiotropic genes to the two said disorders, underlying their genetic overlap.</p><p><bold>Methods:</bold> This study recruited 298 boys with ADHD (including 256 family trios of 1 ADHD boy and his 2 biological parents), 134 boys with ASD, 109 boys with both ADHD and ASD, and 232 typically developing boys as community controls. They were aged between 6 and 11 years old.</p><p><bold>Results:</bold> There was no significant difference in allele frequency of a number of single nucleotide polymorphisms (SNPs) in <italic>SHANK2</italic>/<italic>SHANK3</italic> between the three clinical groups (ADHD, ASD, and ADHD + ASD) and between the two control groups (community controls and pseudo-controls), respectively. The three clinical groups and the two control groups were thus, respectively, combined. A comparison between the two aggregated samples identified significant evidence of disease association for three <italic>SHANK2</italic> SNPs with both ADHD and ASD, even after multiple testing correction: rs11236616 (<italic>OR</italic> = 0.762, permuted <italic>p</italic> = 0.0376), rs7106631 (<italic>OR</italic> = 0.720, permuted <italic>p</italic> = 0.0034), and rs9888288 (<italic>OR</italic> = 0.770, permuted <italic>p</italic> = 0.0407). Comparisons among individual groups pointed to a similar trend of findings.</p><p><bold>Conclusion:</bold><italic>SHANK2</italic> could be considered a potential pleiotropic gene underlying the genetic overlap between ADHD and ASD. This might contribute partly to their high comorbidity in the afflicted children.</p>