Mobile genetic elements (MEs) are heritable mutagens that recursively generate structural variants (SVs). ME variants (MEVs) are difficult to genotype and integrate in statistical genetics, obscuring their impact on genome diversification and traits. We developed a tool that accurately genotypes MEVs using short-read whole-genome sequencing (WGS) and applied it to global human populations. We find unexpected population-specific MEV differences, including an Alu insertion distribution distinguishing Japanese from other populations. Integrating MEVs with expression quantitative trait loci (eQTL) maps shows that MEV classes regulate tissue-specific gene expression by shared mechanisms, including creating or attenuating enhancers and recruiting post-transcriptional regulators, supporting class-wide interpretability. MEVs more often associate with gene expression changes than SNVs, thus plausibly impacting traits. Performing genome-wide association study (GWAS) with MEVs pinpoints potential causes of disease risk, including a LINE-1 insertion associated with keloid and fasciitis. This work implicates MEVs as drivers of human divergence and disease risk.

移动遗传元件（ME）是可遗传的诱变剂，可递归地产生结构变体（SV）。ME 变体 (MEV) 很难进行基因分型并整合到统计遗传学中，从而掩盖了它们对基因组多样化和性状的影响。我们开发了一种使用短读长全基因组测序 (WGS) 准确对 MEV 进行基因分型的工具，并将其应用于全球人群。我们发现了意想不到的特定人群 MEV 差异，包括Alu将日本人和其他人群区分开来的插入分布。将 MEV 与表达数量性状位点 (eQTL) 图谱整合表明，MEV 类别通过共享机制调节组织特异性基因表达，包括创建或减弱增强子和招募转录后调节因子，支持类别范围内的可解释性。MEV 比 SNV 更常与基因表达变化相关，因此可能会影响性状。使用 MEV 进行全基因组关联研究 (GWAS) 可查明疾病风险的潜在原因，包括与疤痕疙瘩和筋膜炎相关的 LINE-1 插入。这项工作表明 MEV 是人类分化和疾病风险的驱动因素。