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Using human genetics to understand the phenotypic association between chronotype and breast cancer

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机构: [1]Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. [2]Department of Epidemiology and Health Statistics, School of Public Health, Southwest Medical University, Luzhou, China. [3]Institute for Molecular Medicine, HiLIFE, University of Helsinki, Helsinki, Finland. [4]School of Life Sciences, Sichuan University, Chengdu, China. [5]Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. [6]Department of Iatrical Polymer Material and Artificial Apparatus, School of Polymer Science and Engineering, Sichuan University, Chengdu, China. [7]Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. [8]Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. [9]Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
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关键词: breast cancer causal inference chronotype genetic correlation pleiotropic loci

摘要:
Little is known regarding the shared genetic influences underlying the observed phenotypic association between chronotype and breast cancer in women. Leveraging summary statistics from the hitherto largest genome-wide association study conducted in each trait, we investigated the genetic correlation, pleiotropic loci, and causal relationship of chronotype with overall breast cancer, and with its subtypes defined by the status of oestrogen receptor. We identified a negative genomic correlation between chronotype and overall breast cancer ( r g $$ {r}_g $$  = -0.06, p = 3.00 × 10-4 ), consistent across oestrogen receptor-positive ( r g $$ {r}_g $$  = -0.05, p = 3.30 × 10-3 ) and oestrogen receptor-negative subtypes ( r g $$ {r}_g $$  = -0.05, p = 1.11 × 10-2 ). Five specific genomic regions were further identified as contributing a significant local genetic correlation. Cross-trait meta-analysis identified 78 loci shared between chronotype and breast cancer, of which 23 were novel. Transcriptome-wide association study revealed 13 shared genes, targeting tissues of the nervous, cardiovascular, digestive, and exocrine/endocrine systems. Mendelian randomisation demonstrated a significantly reduced risk of overall breast cancer (odds ratio 0.89, 95% confidence interval 0.83-0.94; p = 1.30 × 10-4 ) for genetically predicted morning chronotype. No reverse causality was found. Our work demonstrates an intrinsic link underlying chronotype and breast cancer, which may provide clues to inform management of sleep habits to improve female health.© 2023 European Sleep Research Society.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 3 区 临床神经病学 3 区 神经科学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 临床神经病学 3 区 神经科学
第一作者:
第一作者机构: [1]Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
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通讯机构: [1]Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. [8]Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. [9]Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
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