J Korean Acad Child Adolesc Psychiatry.  2018 Apr;29(2):62-72. 10.5765/jkacap.2018.29.2.62.

Genome-Wide Analysis Reveals Four Novel Loci for Attention-Deficit Hyperactivity Disorder in Korean Youths

Affiliations
  • 1Department of Psychiatry, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea.
  • 2DNA Link, Inc. Bioinformatics, Seoul, Korea.
  • 3Department of Psychiatry, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. shingubi@amc.seoul.kr
  • 4Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.

Abstract


OBJECTIVES
The molecular mechanisms underlying attention-deficit hyperactivity disorder (ADHD) remain unclear. Therefore, this study aimed to identify the genetic susceptibility loci for ADHD in Korean children with ADHD. We performed a case-control and a family-based genome-wide association study (GWAS), as well as genome-wide quantitative trait locus (QTL) analyses, for two symptom traits.
METHODS
A total of 135 subjects (71 cases and 64 controls), for the case-control analysis, and 54 subjects (27 probands and 27 unaffected siblings), for the family-based analysis, were included.
RESULTS
The genome-wide QTL analysis identified four single nucleotide polymorphisms (SNPs) (rs7684645 near APELA, rs12538843 near YAE1D1 and POU6F2, rs11074258 near MCTP2, and rs34396552 near CIDEA) that were significantly associated with the number of inattention symptoms in ADHD. These SNPs showed possible association with ADHD in the family-based GWAS, and with hyperactivity-impulsivity in genome-wide QTL analyses. Moreover, association signals in the family-based QTL analysis for the number of inattention symptoms were clustered near genes IL10, IL19, SCL5A9, and SKINTL.
CONCLUSION
We have identified four QTLs with genome-wide significance and several promising candidates that could potentially be associated with ADHD (CXCR4, UPF1, SETD5, NALCN-AS1, ERC1, SOX2-OT, FGFR2, ANO4, and TBL1XR1). Further replication studies with larger sample sizes are needed.

Keyword

Attention-deficit hyperactivity disorder; Genome-wide association study; Asian population; Case-control study; Family-based study

MeSH Terms

Adolescent*
Case-Control Studies
Child
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Interleukin-10
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Sample Size
Interleukin-10
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