Mosaic chromosomal alterations (mCAs) are classified as mosaic deletions (loss), copy-neutral loss of heterozygosity (CN-LOH), and duplications (gain), attracting special attention as biological aging-related acquired genetic alterations. While these mCAs have been linked with aging and various diseases, no study has investigated their association with suicide risk which is associated with abnormal biological aging. Here, we examined the association between suicide deaths and mCAs, including mosaic loss of the X (mLOX) and Y chromosomes, by leveraging blood-derived single nucleotide polymorphism-array data. The first (410 suicide decedents and 88,870 controls) and the second (363 suicide decedents and 88,870 controls) cohorts were analyzed and integrated using meta-analyses (773 suicide decedents and 177,740 controls). Total mCAs in autosomal chromosomes were significantly increased in suicide (p = 1.28 × 10⁻⁶, odds ratio [OR] = 1.78), mostly driven by loss (p = 4.05 × 10⁻⁹, OR = 2.70) and gain (p = 1.08 × 10⁻³, OR = 2.23). mLOX were significantly increased in female suicide (p = 2.66 × 10⁻²¹, OR = 4.00). The directions of effects of all mCAs in autosomal and sex chromosomes on suicide were the same in the first and second sets. Subgroup analyses suggest that our findings were mostly driven by suicide itself, and not confounded by comorbid psychiatric disorders or physical diseases, smoking status, sample location, or postmortem sample status. In conclusion, we provide the first evidence for aberrant mCAs in somatic autosomal and X chromosomes in suicide, which may contribute to an improved understanding of the genomic pathophysiology underlying suicide.

镶嵌染色体改变（mCA）分为镶嵌缺失（丢失）、复制中性杂合性丢失（CN-LOH）和重复（增加），作为与生物衰老相关的获得性遗传改变而受到特别关注。虽然这些 mCA 与衰老和各种疾病有关，但没有研究调查它们与自杀风险的关系，自杀风险与异常的生物衰老有关。在这里，我们通过利用血液来源的单核苷酸多态性阵列数据，研究了自杀死亡与 mCA 之间的关联，包括 X (mLOX) 和 Y 染色体的镶嵌丢失。使用荟萃分析（773 名自杀死者和 177,740 名对照）对第一组（410 名自杀死者和 88,870 名对照）和第二组（363 名自杀死者和 88,870 名对照）进行分析和整合。自杀者常染色体染色体中的总 mCA 显着增加（p = 1.28 × 10 ^-6 ，比值比 [OR] = 1.78），主要是由损失（p = 4.05 × 10 ^-9 ，OR = 2.70）和增加（p = 1.08 × 10 ^-3 ，或= 2.23）。女性自杀者的 mLOX 显着增加（p = 2.66 × 10 ^-21 ，OR = 4.00）。常染色体和性染色体中所有 mCA 对自杀的影响方向在第一组和第二组中是相同的。亚组分析表明，我们的研究结果主要是由自杀本身驱动的，而不是与合并的精神疾病或身体疾病、吸烟状况、样本位置或死后样本状态相混淆。总之，我们提供了自杀中体细胞常染色体和 X 染色体异常 mCA 的第一个证据，这可能有助于更好地了解自杀背后的基因组病理生理学。