Multiomic QTL mapping reveals phenotypic complexity of GWAS loci and prioritizes putative causal variants.

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Tác giả: Timothy D Arthur, Matteo D'Antonio, Agnieszka D'Antonio-Chronowska, Kelly A Frazer, Benjamin A Henson, Juan Carlos Izpisua Belmonte, Jeffrey Jaureguy, Graham McVicker, Jennifer P Nguyen, Athanasia D Panopoulos, Nayara Silva

Ngôn ngữ: eng

Ký hiệu phân loại: 272.3 Persecutions of Waldenses and Albigenses

Thông tin xuất bản: United States : Cell genomics , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 552207

 Most GWAS loci are presumed to affect gene regulation
  however, only ∼43% colocalize with expression quantitative trait loci (eQTLs). To address this colocalization gap, we map eQTLs, chromatin accessibility QTLs (caQTLs), and histone acetylation QTLs (haQTLs) using molecular samples from three early developmental-like tissues. Through colocalization, we annotate 10.4% (n = 540) of GWAS loci in 15 traits by QTL phenotype, temporal specificity, and complexity. We show that integration of chromatin QTLs results in a 2.3-fold higher annotation rate of GWAS loci because they capture distal GWAS loci missed by eQTLs, and that 5.4% (n = 13) of GWAS colocalizing eQTLs are early developmental specific. Finally, we utilize the iPSCORE multiomic QTLs to prioritize putative causal variants overlapping transcription factor motifs to elucidate the potential genetic underpinnings of 296 GWAS-QTL colocalizations.
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