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KTN1 variants and risk for attention deficit hyperactivity disorder.

Xingguang Luo1,2, Xiaoyun Guo3, Yunlong Tan1

  • 1Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China.

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
|March 20, 2020
PubMed
Summary

Genetic variants in the KTN1 gene are significantly associated with attention deficit hyperactivity disorder (ADHD). These KTN1 variants may influence brain structure, specifically the putamen, and play a role in ADHD development.

Keywords:
KTN1ADHDgray matter volumeputamentranscriptiontransposon

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Area of Science:

  • Neurogenetics
  • Psychiatric Disorders

Background:

  • Individuals with attention deficit hyperactivity disorder (ADHD) exhibit reduced gray matter volume (GMV) in the putamen.
  • The KTN1 gene and its variants are hypothesized to regulate kinectin 1 expression, potentially impacting putamen structure and function.

Purpose of the Study:

  • To investigate whether KTN1 gene variants represent a genetic risk factor for ADHD.
  • To explore the association between KTN1 single nucleotide polymorphisms (SNPs) and ADHD in Caucasian family-based samples.

Main Methods:

  • Analysis of 143 KTN1 SNPs in 922 parent-child trios (2,757 subjects).
  • Identification and replication of significant risk SNPs and haplotype blocks in an independent sample of 735 trios (1,383 subjects).
  • Bioinformatics analysis of risk SNPs, assessment of their effect on putamen volume, and examination of KTN1 mRNA expression in human putamen tissue.

Main Results:

  • Fifteen SNPs showed nominal association with ADHD, with three remaining significant after multiple testing correction.
  • These risk SNPs were located in five haplotype blocks, with 13 SNPs and six haplotypes showing significant association in the replication sample.
  • Risk variants were linked to disease-related regions and significantly increased putamen volumes; KTN1 mRNA was expressed in the putamen.

Conclusions:

  • KTN1 gene variants are significantly associated with ADHD, suggesting a genetic link.
  • KTN1 may play a functional role in the neurobiological underpinnings of ADHD, potentially through its influence on putamen structure.