Shared heritability and functional enrichment across six solid cancers
説明
<jats:title>Abstract</jats:title><jats:p>Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub> = 0.57, <jats:italic>p</jats:italic> = 4.6 × 10<jats:sup>−8</jats:sup>), breast and ovarian cancer (<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub> = 0.24, <jats:italic>p</jats:italic> = 7 × 10<jats:sup>−5</jats:sup>), breast and lung cancer (<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub> = 0.18, <jats:italic>p </jats:italic>=1.5 × 10<jats:sup>−6</jats:sup>) and breast and colorectal cancer (<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub> = 0.15, <jats:italic>p</jats:italic> = 1.1 × 10<jats:sup>−4</jats:sup>). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.</jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 10 (1), 2019-01-25
Springer Science and Business Media LLC
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キーワード
- Male
- Lung Neoplasms
- Inheritance Patterns
- Colorectal Neoplasms/diagnosis
- Càncer - Aspectes genètics
- /dk/atira/pure/core/keywords/icep
- Neoplasm Proteins/genetics
- PARTITIONING HERITABILITY
- Càncer
- Cancer
- Prostatic Neoplasms/diagnosis
- Càncer - Estudi de casos
- Ovarian Neoplasms
- :Otros calificadores::Otros calificadores::/genética [Otros calificadores]
- Neoplasm Proteins
- Genetics, developmental biology, physiology
- Head and Neck Neoplasms
- Etiologia
- :Neoplasias [ENFERMEDADES]
- ICEP
- /dk/atira/pure/core/keywords/centre_for_surgical_research
- Cancers
- :Genetic Phenomena::Inheritance Patterns [PHENOMENA AND PROCESSES]
- Biolääketieteet - Biomedicine
- Lung Neoplasms/diagnosis
- Science
- European Continental Ancestry Group
- 610
- Article
- White People
- GENETIC ARCHITECTURE
- :neoplasias [ENFERMEDADES]
- SDG 3 - Good Health and Well-being
- Syöpätaudit - Cancers
- 616
- BREAST-CANCER
- Humans
- :Otros calificadores::Otros calificadores::Otros calificadores::/etnología [Otros calificadores]
- Polymorphism
- GENOME-WIDE ASSOCIATION
- ANALYSES IDENTIFY
- :Fenómenos Genéticos::Patrón de Herencia [FENÓMENOS Y PROCESOS]
- 500
- Biology and Life Sciences
- :fenómenos genéticos::patrones de herencia [FENÓMENOS Y PROCESOS]
- /dk/atira/pure/core/keywords/centre_for_surgical_research; name=Centre for Surgical Research
- genetic architecture
- ResearchInstitutes_Networks_Beacons/mcrc; name=Manchester Cancer Research Centre
- susceptibility loci
- cell-types
- Biomedicine
- Càncer -- Etiologia
- Case-Control Studies
- General Biochemistry
- RISK-FACTORS
- mendelian randomization
- IDIS
- Etiology
- Medizin
- General Physics and Astronomy
- :técnicas de investigación::métodos epidemiológicos::características de los estudios epidemiológicos::estudios epidemiológicos::estudios de casos y controles [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]
- head and neck
- partitioning heritability
- Medicine and Health Sciences
- risk-factors
- Càncer -- Aspectes genètics
- Mental Disorders
- Q
- Codi genètic
- Smoking
- Single Nucleotide
- Phenotype
- Centre for Surgical Research
- Cancer -- Etiology
- MENDELIAN RANDOMIZATION
- Smoking/ethnology
- Female
- analyses identify
- Mental Disorders/ethnology
- Colorectal Neoplasms
- Medical Genetics
- CHUS
- :Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics::Epidemiologic Studies::Case-Control Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT]
- :Técnicas de Investigación::Métodos Epidemiológicos::Características de Estudios Epidemiológicos::Estudios Epidemiológicos::Estudios de Casos y Controles [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]
- SUSCEPTIBILITY LOCI
- Genetics and Molecular Biology
- Breast Neoplasms
- Radboudumc 15: Urological cancers RIHS: Radboud Institute for Health Sciences
- Polymorphism, Single Nucleotide
- All institutes and research themes of the Radboud University Medical Center
- LUNG-CANCER
- :Other subheadings::Other subheadings::/genetics [Other subheadings]
- Genetic Predisposition to Disease
- CELL-TYPES
- breast-cancer
- Medicinsk genetik
- /dk/atira/pure/core/keywords/icep; name=ICEP
- Ovarian Neoplasms/diagnosis
- Breast Neoplasms/diagnosis
- Prostatic Neoplasms
- General Chemistry
- Head and Neck Neoplasms/diagnosis
- :Neoplasms [DISEASES]
- genome-wide association
- lung-cancer
- Breast Neoplasms; Case-Control Studies; Colorectal Neoplasms; European Continental Ancestry Group; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Mental Disorders; Neoplasm Proteins; Ovarian Neoplasms; Phenotype; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Smoking; Inheritance Patterns
- :Other subheadings::Other subheadings::Other subheadings::/ethnology [Other subheadings]
- Genome-Wide Association Study
