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Genetic Basis of Alternative Polyadenylation as an Emerging Molecular Phenotype for Human Traits and Diseases

ABSTRACT: Genetic Basis of Alternative Polyadenylation as an Emerging Molecular Phenotype for Human Traits and Diseases

PROVIDER: PRJNA580238 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10359916.fastq.gz	Fastqsanger.gz
	SRR10359917.fastq.gz	Fastqsanger.gz
	SRR10359918.fastq.gz	Fastqsanger.gz
	SRR10359919.fastq.gz	Fastqsanger.gz
	SRR10359920.fastq.gz	Fastqsanger.gz

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Genetic Basis of Alternative Polyadenylation as an Emerging Molecular Phenotype for Human Traits and Diseases

Project description:Genome-wide association studies have identified thousands of non-coding variants that are statistically associated with human traits and diseases. However, functional interpretation of these variants remains a major challenge. Here, we describe the first atlas of human 3’-UTR alternative polyadenylation (APA) Quantitative Trait Loci (3′aQTLs), i.e. ~0.4 million genetic variants associated with APA of target genes across 46 Genotype-Tissue Expression (GTEx) tissues from 467 individuals. APA occurs in approximately 70% of human genes and substantively impacts cellular proliferation, differentiation and tumorigenesis. Mechanistically, 3′aQTLs could alter polyA motifs and RNA-binding protein binding sites, leading to thousands of APA changes. Importantly, 3′aQTLs can be used to interpret ~16.1% of trait-associated variants and are largely distinct from other QTLs such as eQTLs. These 3′aQTLs thus represent the genetic basis of APA as a novel molecular phenotype to explain a large fraction of non-coding variants and to provide new insights into complex traits and disease etiologies.

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