Rare variants in SLC6A4 cause susceptibility to major depressive disorder with suicidal ideation in Han Chinese adolescents and young adults

Liuyi Ran; Ming Ai; Wo Wang; Jianmei Chen; Tong Wu; Wei Liu; Jiajia Jin; Suya Wang; Li Kuang

doi:10.1016/j.gene.2019.144147

Rare variants in SLC6A4 cause susceptibility to major depressive disorder with suicidal ideation in Han Chinese adolescents and young adults

Gene. 2020 Feb 5:726:144147. doi: 10.1016/j.gene.2019.144147. Epub 2019 Oct 17.

Authors

Liuyi Ran¹, Ming Ai², Wo Wang¹, Jianmei Chen², Tong Wu¹, Wei Liu¹, Jiajia Jin¹, Suya Wang¹, Li Kuang³

Affiliations

¹ Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China.
² Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
³ Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China; Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: kuangli0308@163.com.

PMID: 31629822
DOI: 10.1016/j.gene.2019.144147

Abstract

Background: Suicidal ideation (SI) is the most serious symptom of major depressive disorder (MDD) and considered an extreme state. The serotonin transporter gene (SLC6A4) plays a significant role in MDD and suicide pathophysiology. Previous studies have revealed an association between common variants of SLC6A4 with the risk of MDD and suicide. However, very few studies have so far focused on the degree to which rare variants of SLC6A4 are responsible for the depression observed in adolescent and young adult suicide patients. The aim of this study was to examine the impact of common and rare variants of SLC6A4 on the risk of Han Chinese adolescents and young adults suffering MDD with SI.

Methods: Targeted sequencing of the SLC6A4 gene was conducted using FastTarget technology in Han Chinese adolescents and young adults, of which 74 were MDD patients with SI and 150 were healthy controls. Gene-based association analyses of rare variants were performed using enrichment analysis and a cumulative allele test. An allele association study was performed against common variants.

Results: After sequencing and bioinformatics analysis, a total of 15 single nucleotide variants (SNVs) were detected in the targeted regions from all participants, including 9 common and 6 rare variants. Among these, 5 rare variants were identified within the study group. Enrichment analysis of rare variants demonstrated a statistical difference (p = 0.042) between the study and control groups. Using cumulative allele analysis, alternative alleles in the SLC6A4 gene exhibited an association with MDD patients with SI (cumulative allele: OR = 10.18, 95% CI = 1.18-87.32, p = 0.017). No significant association was found between the 9 common SLC6A4 variants and MDD patients with SI.

Conclusions: Our results suggest that rare variants of SLC6A4 may contribute to a genetic risk of adolescents and young adults suffering MDD with SI.

Keywords: Adolescents and young adults; Common variants; Han Chinese; Major depressive disorder; Rare variants; SLC6A4; Suicidal ideation; Targeted sequencing.

MeSH terms

Adolescent
Adult
Alleles
Asian People / genetics*
Depressive Disorder, Major / genetics*
Female
Genetic Predisposition to Disease / genetics*
Genetic Testing / methods
Humans
Male
Polymorphism, Single Nucleotide / genetics*
Risk Factors
Serotonin Plasma Membrane Transport Proteins / genetics*
Suicidal Ideation
Suicide
Young Adult

Substances

SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins