日本东京大学Qingbo S. Wang等研究人员合作发现，来自1405名人类的统计和功能精细定位血液eQTL和pQTL，揭示不同的调控模式和疾病相关性。相关论文于2024年9月24日在线发表在《自然—遗传学》杂志上。

研究人员报告了来自1405个基因分型样本的顺式表达数量性状基因位点（eQTL）和蛋白质数量性状基因位点（pQTL）统计精细定位，结合了血液mRNA和2932个蛋白质表达的血浆样本，作为日本COVID-19工作组（JCTF）的一部分。精细定位的eQTL（n=3464）富集了932个通过大规模平行报告测定验证的变异体。

精细定位的pQTL（n=582）富集了在结构域和细胞外域上的错义变异，尽管仍存在表位结合伪影的可能性。转式eQTL和pQTL分析突出了I类HLA等位基因变异与KIR基因之间的关联。

研究人员对比了血浆蛋白质与血液mRNA的多组织来源，阐明了eQTL和pQTL的有限共定位水平、不同的调控机制和性状相关性。研究人员报告了ABO mRNA与蛋白质表达之间的负相关，因不同的附近eQTL和pQTL之间的连锁不平衡。

据悉，研究蛋白质表达的遗传调控（通过pQTL）能够更深入地理解mRNA表达调控（eQTL）研究未表征的调控变体。

附：英文原文

Title: Statistically and functionally fine-mapped blood eQTLs and pQTLs from 1,405 humans reveal distinct regulation patterns and disease relevance

Author: Wang, Qingbo S., Hasegawa, Takanori, Namkoong, Ho, Saiki, Ryunosuke, Edahiro, Ryuya, Sonehara, Kyuto, Tanaka, Hiromu, Azekawa, Shuhei, Chubachi, Shotaro, Takahashi, Yugo, Sakaue, Saori, Namba, Shinichi, Yamamoto, Kenichi, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Makishima, Hideki, Nannya, Yasuhito, Zhang, Zicong, Tsujikawa, Rika, Koike, Ryuji, Takano, Tomomi, Ishii, Makoto, Kimura, Akinori, Inoue, Fumitaka, Kanai, Takanori, Fukunaga, Koichi, Ogawa, Seishi, Imoto, Seiya, Miyano, Satoru, Okada, Yukinori

Issue&Volume: 2024-09-24

Abstract: Studying the genetic regulation of protein expression (through protein quantitative trait loci (pQTLs)) offers a deeper understanding of regulatory variants uncharacterized by mRNA expression regulation (expression QTLs (eQTLs)) studies. Here we report cis-eQTL and cis-pQTL statistical fine-mapping from 1,405 genotyped samples with blood mRNA and 2,932 plasma samples of protein expression, as part of the Japan COVID-19 Task Force (JCTF). Fine-mapped eQTLs (n=3,464) were enriched for 932 variants validated with a massively parallel reporter assay. Fine-mapped pQTLs (n=582) were enriched for missense variations on structured and extracellular domains, although the possibility of epitope-binding artifacts remains. Trans-eQTL and trans-pQTL analysis highlighted associations of class I HLA allele variation with KIR genes. We contrast the multi-tissue origin of plasma protein with blood mRNA, contributing to the limited colocalization level, distinct regulatory mechanisms and trait relevance of eQTLs and pQTLs. We report a negative correlation between ABO mRNA and protein expression because of linkage disequilibrium between distinct nearby eQTLs and pQTLs.

DOI: 10.1038/s41588-024-01896-3

Source: https://www.nature.com/articles/s41588-024-01896-3