ArticleScientific reports2021
Genetic association studies of alterations in protein function expose recessive effects on cancer predisposition.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Multi-ancestry meta-analysis of keloids uncovers novel susceptibility loci in diverse populations.Nature communications · 2025Pooled it
- Integrative Gene-Centric Analysis Reveals Cellular Pathways Associated with Heritable Breast Cancer Predisposition.Cancers · 2025Article
- Proteome-wide association study of prostate cancer risk across populations.Nature communications · 2025Article
- Emerging multifaceted roles of the microbiome in cancer susceptibility.World journal of clinical oncology · 2025Review
- Local Genetic Correlations and Pleiotropy Reveal Shared Genetic Architecture Between COVID-19 Phenotypes and Prostate Cancer in European Populations.Journal of Cancer · 2025Article
- PWAS Hub for exploring gene-based associations of common complex diseases.Genome research · 2024Article
- Ancestral origins and post-admixture adaptive evolution of highland Tajiks.National science review · 2024Article
- An Inherited Allele Confers Prostate Cancer Progression and Drug Resistance via RFX6/HOXA10-Orchestrated TGFβ Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Common and novel haplotype structures between different types of cancer.Cancer reports (Hoboken, N.J.) · 2024Article
- Novel genetic association between obesity, colorectal cancer, and inflammatory bowel disease.Journal of diabetes and metabolic disorders · 2024Article
- rs2736098, a synonymous polymorphism, is associated with carcinogenesis and cell count in multiple tissue types by regulatingHeliyon · 2024Article
- Epigenome-wide association study identifies neonatal DNA methylation associated with two-year attention problems in children born very preterm.Translational psychiatry · 2024Article
- Revealing the genetic complexity of hypothyroidism: integrating complementary association methods.Frontiers in genetics · 2024Article
- Investigation of common genetic risk factors between thyroid traits and breast cancer.Human molecular genetics · 2023Article
- Genome-wide prediction of disease variant effects with a deep protein language model.Nature genetics · 2023Article
- Gene-based association study reveals a distinct female genetic signal in primary hypertension.Human genetics · 2023Article
- Explainable multi-task learning improves the parallel estimation of polygenic risk scores for many diseases through shared genetic basis.PLoS computational biology · 2023Article
- Long-Term Simulation of Microgravity Induces Changes in Gene Expression in Breast Cancer Cells.International journal of molecular sciences · 2023Article
- Parent-of-Origin inference for biobanks.Nature communications · 2022Article
- Open problems in human trait genetics.Genome biology · 2022Review
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3 authors.
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Abstract
The characterization of germline genetic variation affecting cancer risk, known as cancer predisposition, is fundamental to preventive and personalized medicine. Studies of genetic cancer predisposition typically identify significant genomic regions based on family-based cohorts or genome-wide association studies (GWAS). However, the results of such studies rarely provide biological insight or functional interpretation. In this study, we conducted a comprehensive analysis of cancer predisposition in the UK Biobank cohort using a new gene-based method for detecting protein-coding genes that are functionally interpretable. Specifically, we conducted proteome-wide association studies (PWAS) to identify genetic associations mediated by alterations to protein function. With PWAS, we identified 110 significant gene-cancer associations in 70 unique genomic regions across nine cancer types and pan-cancer. In 48 of the 110 PWAS associations (44%), estimated gene damage is associated with reduced rather than elevated cancer risk, suggesting a protective effect. Together with standard GWAS, we implicated 145 unique genomic loci with cancer risk. While most of these genomic regions are supported by external evidence, our results also highlight many novel loci. Based on the capacity of PWAS to detect non-additive genetic effects, we found that 46% of the PWAS-significant cancer regions exhibited exclusive recessive inheritance. These results highlight the importance of recessive genetic effects, without relying on familial studies. Finally, we show that many of the detected genes exert substantial cancer risk in the studied cohort determined by a quantitative functional description, suggesting their relevance for diagnosis and genetic consulting.
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