Parikh Kairavi, Quintero Reis Andrea, Wendt Frank R
Forensic Science Program, University of Toronto, Mississauga, ON, Canada.
Biostatistics Division, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Front Psychiatry. 2024 Jan 4;14:1236540. doi: 10.3389/fpsyt.2023.1236540. eCollection 2023.
Death by suicide is one of the leading causes of death among adolescents. Genome-wide association studies (GWAS) have identified loci that associate with suicidal ideation and related behaviours. One such group of loci are the six genes () that are critical to neurodevelopment through regulating neurite structure. Because single nucleotide polymorphisms (SNPs) detected by GWAS often map to non-coding intergenic regions, we investigated whether repetitive variants in s associated with suicidality in a young cohort aged 8 to 21. Understanding the genetic liability of suicidal thought and behavior in this age group will promote early intervention and treatment.
Genotypic and phenotypic data were obtained from the Philadelphia Neurodevelopment Cohort (PNC). Across six s, 232 short tandem repeats (STRs) were analyzed in up to 4,595 individuals of European ancestry who expressed current, previous, or no suicidal ideation. STRs were imputed into SNP arrays using a phased SNP-STR haplotype reference panel from the 1000 Genomes Project. We tested several additive and interactive models of locus-level burden (i.e., sum of STR alleles) with respect to suicidal ideation. Additive models included sex, birth year, developmental stage ("DevStage"), and the first 10 principal components of ancestry as covariates; interactive models assessed the effect of STR-by-DevStage considering all other covariates.
-[T] interacted with DevStage to increase risk for current suicidal ideation (-[T]-by-DevStage; = 0.00035). Compared to the youngest age group, the middle (OR = 1.80, = 0.0514) and oldest (OR = 3.82, = 0.0002) participant groups had significantly higher odds of suicidal ideation as their STR length expanded; this result was independent of polygenic scores for suicidal ideation.
These findings highlight diversity in the genetic effects (i.e., SNP and STR) acting on suicidal thoughts and behavior and advance our understanding of suicidal ideation across childhood and adolescence.
自杀是青少年主要的死亡原因之一。全基因组关联研究（GWAS）已经确定了与自杀意念及相关行为相关的基因座。其中一组这样的基因座是六个基因（），它们通过调节神经突结构对神经发育至关重要。由于GWAS检测到的单核苷酸多态性（SNP）通常映射到非编码基因间区域，我们调查了在8至21岁的年轻队列中，基因中的重复变异是否与自杀倾向有关。了解该年龄组自杀念头和行为的遗传易感性将促进早期干预和治疗。
从费城神经发育队列（PNC）获得基因型和表型数据。在六个基因中，对多达4595名有当前、既往或无自杀意念的欧洲血统个体分析了232个短串联重复序列（STR）。使用来自千人基因组计划的分阶段SNP-STR单倍型参考面板将STR推算到SNP阵列中。我们测试了几种关于自杀意念的基因座水平负担（即STR等位基因总和）的加性和交互模型。加性模型包括性别、出生年份、发育阶段（“DevStage”）以及祖先的前10个主成分作为协变量；交互模型在考虑所有其他协变量的情况下评估STR与发育阶段的相互作用。
-[T]与发育阶段相互作用，增加了当前自杀意念的风险（-[T]-与发育阶段； = 0.00035）。与最年轻的年龄组相比，中年（OR = 1.80， = 0.0514）和老年（OR = 3.82， = 0.0002）参与者组随着STR长度的增加，自杀意念的几率显著更高；这一结果独立于自杀意念的多基因评分。
这些发现突出了影响自杀念头和行为的遗传效应（即SNP和STR）的多样性，并推进了我们对儿童期和青春期自杀意念的理解。
