Children and Young People's Mental Health Research Collaboration (ChYMe), University of Exeter College of Medicine and Health, Exeter, UK.
MRC Integrative Epidemiology Unit, University of Bristol Medical School, Bristol, UK.
BMC Psychiatry. 2021 Apr 23;21(1):207. doi: 10.1186/s12888-021-03216-z.
Empirical evidence supporting the distinction between suicide attempt (SA) and non-suicidal self-harm (NSSH) is lacking. Although NSSH is a risk factor for SA, we do not currently know whether these behaviours lie on a continuum of severity, or whether they are discrete outcomes with different aetiologies. We conducted this exploratory genetic epidemiology study to investigate this issue further.
We explored the extent of genetic overlap between NSSH and SA in a large, richly-phenotyped cohort (the Avon Longitudinal Study of Parents and Children; N = 4959), utilising individual-level genetic and phenotypic data to conduct analyses of genome-wide complex traits and polygenic risk scores (PRS).
The single nucleotide polymorphism heritability of NSSH was estimated to be 13% (SE 0.07) and that of SA to be 0% (SE 0.07). Of the traits investigated, NSSH was most strongly correlated with higher IQ (rG = 0.31, SE = 0.22), there was little evidence of high genetic correlation between NSSH and SA (rG = - 0.1, SE = 0.54), likely due to the low heritability estimate for SA. The PRS for depression differentiated between those with NSSH and SA in multinomial regression. The optimal PRS prediction model for SA (Nagelkerke R 0.022, p < 0.001) included ADHD, depression, income, anorexia and neuroticism and explained more variance than the optimal prediction model for NSSH (Nagelkerke R 0.010, p < 0.001) which included ADHD, alcohol consumption, autism spectrum conditions, depression, IQ, neuroticism and suicide attempt.
Our findings suggest that SA does not have a large genetic component, and that although NSSH and SA are not discrete outcomes there appears to be little genetic overlap between the two. The relatively small sample size and resulting low heritability estimate for SA was a limitation of the study. Combined with low heritability estimates, this implies that family or population structures in SA GWASs may contribute to signals detected.
缺乏支持自杀未遂（SA）和非自杀性自伤（NSSH）之间区别的实证证据。虽然 NSSH 是自杀的风险因素，但我们目前尚不清楚这些行为是否处于严重程度的连续体上，或者它们是否是具有不同病因的离散结果。我们进行了这项探索性遗传流行病学研究，以进一步探讨这个问题。
我们利用个体水平的遗传和表型数据，在一个大型、表型丰富的队列（阿冯纵向研究父母和孩子；N=4959）中，探索了 NSSH 和 SA 之间遗传重叠的程度，利用全基因组复杂性状和多基因风险评分（PRS）进行分析。
NSSH 的单核苷酸多态性遗传率估计为 13%（SE 0.07），SA 的遗传率估计为 0%（SE 0.07）。在所研究的性状中，NSSH 与较高的智商相关性最强（rG=0.31，SE=0.22），NSSH 和 SA 之间几乎没有高遗传相关性的证据（rG=-0.1，SE=0.54），这可能是由于 SA 的遗传率估计较低。抑郁的 PRS 在多项回归中区分了 NSSH 和 SA。SA 的最佳 PRS 预测模型（Nagelkerke R 0.022，p<0.001）包括 ADHD、抑郁、收入、厌食症和神经质，并且比 NSSH 的最佳预测模型（Nagelkerke R 0.010，p<0.001）解释了更多的方差，后者包括 ADHD、饮酒、自闭症谱系障碍、抑郁、智商、神经质和自杀未遂。
我们的研究结果表明，SA 没有很大的遗传成分，尽管 NSSH 和 SA 不是离散的结果，但两者之间似乎没有太多的遗传重叠。SA 的样本量相对较小和由此产生的遗传率估计值较低是该研究的一个局限性。结合低遗传率估计值，这意味着 SA GWAS 中的家族或人群结构可能会导致检测到的信号。
