Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.
Cell Genom. 2023 Dec 13;3(12):100458. doi: 10.1016/j.xgen.2023.100458.
Short tandem repeats (STRs) are genomic regions consisting of repeated sequences of 1-6 bp in succession. Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) do not fully capture STR effects. To study these effects, we imputed 445,720 STRs into genotype arrays from 408,153 White British UK Biobank participants and tested for association with 44 blood phenotypes. Using two fine-mapping methods, we identify 119 candidate causal STR-trait associations and estimate that STRs account for 5.2%-7.6% of causal variants identifiable from GWASs for these traits. These are among the strongest associations for multiple phenotypes, including a coding CTG repeat associated with apolipoprotein B levels, a promoter CGG repeat with platelet traits, and an intronic poly(A) repeat with mean platelet volume. Our study suggests that STRs make widespread contributions to complex traits, provides stringently selected candidate causal STRs, and demonstrates the need to consider a more complete view of genetic variation in GWASs.
短串联重复序列（STRs）是由连续重复 1-6bp 的序列组成的基因组区域。基于单核苷酸多态性（SNP）的全基因组关联研究（GWAS）不能完全捕捉 STR 效应。为了研究这些效应，我们将 445720 个 STR 导入来自 408153 名英国白人 UK Biobank 参与者的基因分型阵列中，并测试它们与 44 种血液表型的关联。使用两种精细映射方法，我们确定了 119 个候选因果 STR-表型关联，并估计 STR 占这些表型的 GWAS 中可识别因果变异的 5.2%-7.6%。这些是针对多种表型的最强关联之一，包括与载脂蛋白 B 水平相关的编码 CTG 重复，与血小板特征相关的启动子 CGG 重复以及与平均血小板体积相关的内含子多（A）重复。我们的研究表明，STR 广泛影响复杂特征，提供了严格选择的候选因果 STR，并证明需要在 GWAS 中考虑更全面的遗传变异视图。
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