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000289896 1001_ $$aChen, Zhishan$$b0
000289896 245__ $$aFine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.
000289896 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000289896 520__ $$aGenome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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000289896 650_2 $$2MeSH$$aHumans
000289896 650_2 $$2MeSH$$aColorectal Neoplasms: genetics
000289896 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000289896 650_2 $$2MeSH$$aGenome-Wide Association Study
000289896 650_2 $$2MeSH$$aAsian People: genetics
000289896 650_2 $$2MeSH$$aWhite People: genetics
000289896 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide
000289896 650_2 $$2MeSH$$aQuantitative Trait Loci
000289896 650_2 $$2MeSH$$aExome Sequencing
000289896 650_2 $$2MeSH$$aCase-Control Studies
000289896 650_2 $$2MeSH$$aTranscriptome
000289896 650_2 $$2MeSH$$aChromosome Mapping
000289896 650_2 $$2MeSH$$aMale
000289896 650_2 $$2MeSH$$aFemale
000289896 650_2 $$2MeSH$$aEast Asian People
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