Genome-wide analysis of 3' untranslated region alternative polyadenylation quantitative trait loci identified a potential novel susceptibility locus for lung cancer in cross-ancestry populations.

Yi Wang, Yuancheng Li, Ting Tian, Renfang Han, Nimei Zeng, Fangfei Xie, Yun Wang, Jingyi Fan

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Article in Journal of human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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8 authors.

Yi Wang *Health Management Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

Yuancheng Li *Central Research Laboratory, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China.

Ting TianCentral Research Laboratory, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China.

Renfang HanHealth Management Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

Nimei ZengHealth Management Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

Fangfei XieHealth Management Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

Yun WangHealth Management Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. xsky1906@163.com.

Jingyi FanHealth Management Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. fanjingyi@njmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genome wide association studies (GWASs) have revealed several lung cancer susceptibility loci; however, we still face key issues such as how to identify more 'high-frequency and inefficient' variants and decipher the causal variants. Alternative polyadenylation (APA) can shorten or prolong the 3'UTR of mRNA containing cis regulatory elements, which plays an important role in post transcriptional regulation. Specific variants can affect the 3'UTR APA, leading to differences in the risk of lung cancer among individuals carrying different alleles. In this study, a cross-ancestry two-stage case-control design was used to evaluate the associations of 3'UTR APA related variants (3'aQTL SNPs, 3'aSNPs) defined by GTEx in normal lung tissues with the risk of lung cancer based on the genome-wide meta-analysis (GWMA) from FinnGen, UK Biobank and VA Million Veteran Program (MVP), including 28,557 cases and 1,355,961 controls. The promising variants were validated in an independent Chinese population with 1169 lung cancer cases and 1046 controls. Functional annotations of the identified 3'aSNP and related genes were performed based on multiple public databases. Finally, we identified a potential 3'aSNP rs11583258 associated with the risk of lung cancer both in the GWMA [OR = 1.04 (1.02-1.06), P = 1.00 × 10

Indexed as

3' Untranslated RegionsGenetic Predisposition to DiseaseLung NeoplasmsPolyadenylationQuantitative Trait LociAgedCase-Control StudiesFemaleGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single Nucleotide3' Untranslated Regions

Identifiers

PMID40730666

DOI10.1007/s10620-024-08414-9

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.