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Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study.

Identifieur interne : 000524 ( Main/Exploration ); précédent : 000523; suivant : 000525

Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study.

Auteurs : Rebecca C. Richmond [Royaume-Uni] ; Emma L. Anderson [Royaume-Uni] ; Hassan S. Dashti [États-Unis] ; Samuel E. Jones [Royaume-Uni] ; Jacqueline M. Lane [États-Unis] ; Linn Beate Strand [Norvège] ; Ben Brumpton [Norvège] ; Martin K. Rutter [Royaume-Uni] ; Andrew R. Wood [Royaume-Uni] ; Kurt Straif [France] ; Caroline L. Relton [Royaume-Uni] ; Marcus Munaf [Royaume-Uni] ; Timothy M. Frayling [Royaume-Uni] ; Richard M. Martin [Royaume-Uni] ; Richa Saxena [États-Unis] ; Michael N. Weedon [Royaume-Uni] ; Debbie A. Lawlor [Royaume-Uni] ; George Davey Smith [Royaume-Uni]

Source :

RBID : pubmed:31243001

Descripteurs français

English descriptors

Abstract

OBJECTIVE

To examine whether sleep traits have a causal effect on risk of breast cancer.

DESIGN

Mendelian randomisation study.

SETTING

UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.

PARTICIPANTS

156 848 women in the multivariable regression and one sample mendelian randomisation (MR) analysis in UK Biobank (7784 with a breast cancer diagnosis) and 122 977 breast cancer cases and 105 974 controls from BCAC in the two sample MR analysis.

EXPOSURES

Self reported chronotype (morning or evening preference), insomnia symptoms, and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits.

MAIN OUTCOME MEASURE

Breast cancer diagnosis.

RESULTS

In multivariable regression analysis using UK Biobank data on breast cancer incidence, morning preference was inversely associated with breast cancer (hazard ratio 0.95, 95% confidence interval 0.93 to 0.98 per category increase), whereas there was little evidence for an association between sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated with sleep duration, and 57 SNPs associated with insomnia symptoms, one sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (0.85, 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two sample MR using data from BCAC supported findings for a protective effect of morning preference (inverse variance weighted odds ratio 0.88, 95% confidence interval 0.82 to 0.93 per category increase) and adverse effect of increased sleep duration (1.19, 1.02 to 1.39 per hour increase) on breast cancer risk (both oestrogen receptor positive and oestrogen receptor negative), whereas evidence for insomnia symptoms was inconsistent. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy.

CONCLUSIONS

Findings showed consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of increased sleep duration on breast cancer risk.


DOI: 10.1136/bmj.l2327
PubMed: 31243001
PubMed Central: PMC6592406


Affiliations:

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<nlm:affiliation>MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK Rebecca.richmond@bristol.ac.uk.</nlm:affiliation>
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<author>
<name sortKey="Anderson, Emma L" sort="Anderson, Emma L" uniqKey="Anderson E" first="Emma L" last="Anderson">Emma L. Anderson</name>
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<nlm:affiliation>MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.</nlm:affiliation>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
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<nlm:affiliation>Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.</nlm:affiliation>
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<author>
<name sortKey="Dashti, Hassan S" sort="Dashti, Hassan S" uniqKey="Dashti H" first="Hassan S" last="Dashti">Hassan S. Dashti</name>
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<nlm:affiliation>Centre for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<region type="state">Massachusetts</region>
</placeName>
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<affiliation wicri:level="2">
<nlm:affiliation>Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.</nlm:affiliation>
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<wicri:regionArea>Program in Medical and Population Genetics, Broad Institute, Cambridge, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
</placeName>
</affiliation>
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<author>
<name sortKey="Jones, Samuel E" sort="Jones, Samuel E" uniqKey="Jones S" first="Samuel E" last="Jones">Samuel E. Jones</name>
<affiliation wicri:level="1">
<nlm:affiliation>Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.</nlm:affiliation>
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<author>
<name sortKey="Lane, Jacqueline M" sort="Lane, Jacqueline M" uniqKey="Lane J" first="Jacqueline M" last="Lane">Jacqueline M. Lane</name>
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<nlm:affiliation>Centre for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Centre for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
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<affiliation wicri:level="2">
<nlm:affiliation>Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.</nlm:affiliation>
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<wicri:regionArea>Program in Medical and Population Genetics, Broad Institute, Cambridge, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Strand, Linn Beate" sort="Strand, Linn Beate" uniqKey="Strand L" first="Linn Beate" last="Strand">Linn Beate Strand</name>
<affiliation wicri:level="3">
<nlm:affiliation>K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.</nlm:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health sciences, Norwegian University of Science and Technology, NTNU, Trondheim</wicri:regionArea>
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<settlement type="city">Trondheim</settlement>
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<author>
<name sortKey="Brumpton, Ben" sort="Brumpton, Ben" uniqKey="Brumpton B" first="Ben" last="Brumpton">Ben Brumpton</name>
<affiliation wicri:level="3">
<nlm:affiliation>K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.</nlm:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health sciences, Norwegian University of Science and Technology, NTNU, Trondheim</wicri:regionArea>
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<settlement type="city">Trondheim</settlement>
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<affiliation wicri:level="3">
<nlm:affiliation>Clinic of Thoracic and Occupational Medicine, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.</nlm:affiliation>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Clinic of Thoracic and Occupational Medicine, St Olav's Hospital, Trondheim University Hospital, Trondheim</wicri:regionArea>
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<settlement type="city">Trondheim</settlement>
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<name sortKey="Rutter, Martin K" sort="Rutter, Martin K" uniqKey="Rutter M" first="Martin K" last="Rutter">Martin K. Rutter</name>
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<nlm:affiliation>Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Endocrinology, Diabetes and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester</wicri:regionArea>
<placeName>
<settlement type="city">Manchester</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Manchester</region>
</placeName>
<orgName type="university">Université de Manchester</orgName>
</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>Manchester Diabetes Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, Manchester, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Manchester Diabetes Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, Manchester</wicri:regionArea>
<placeName>
<settlement type="city">Manchester</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Manchester</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wood, Andrew R" sort="Wood, Andrew R" uniqKey="Wood A" first="Andrew R" last="Wood">Andrew R. Wood</name>
<affiliation wicri:level="1">
<nlm:affiliation>Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Genetics of Complex Traits, University of Exeter Medical School, Exeter</wicri:regionArea>
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</author>
<author>
<name sortKey="Straif, Kurt" sort="Straif, Kurt" uniqKey="Straif K" first="Kurt" last="Straif">Kurt Straif</name>
<affiliation wicri:level="3">
<nlm:affiliation>International Agency for Research on Cancer, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>International Agency for Research on Cancer, Lyon</wicri:regionArea>
<placeName>
<region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
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</affiliation>
</author>
<author>
<name sortKey="Relton, Caroline L" sort="Relton, Caroline L" uniqKey="Relton C" first="Caroline L" last="Relton">Caroline L. Relton</name>
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<nlm:affiliation>MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
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<orgName type="university">Université de Bristol</orgName>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre du Sud-Ouest</region>
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<nlm:affiliation>Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
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<orgName type="university">Université de Bristol</orgName>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
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<name sortKey="Munaf, Marcus" sort="Munaf, Marcus" uniqKey="Munaf M" first="Marcus" last="Munaf">Marcus Munaf</name>
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<nlm:affiliation>MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre du Sud-Ouest</region>
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</affiliation>
<affiliation wicri:level="4">
<nlm:affiliation>School of Experimental Psychology, University of Bristol, Bristol, UK.</nlm:affiliation>
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<wicri:regionArea>School of Experimental Psychology, University of Bristol, Bristol</wicri:regionArea>
<orgName type="university">Université de Bristol</orgName>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
<region type="country">Angleterre</region>
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<name sortKey="Frayling, Timothy M" sort="Frayling, Timothy M" uniqKey="Frayling T" first="Timothy M" last="Frayling">Timothy M. Frayling</name>
<affiliation wicri:level="1">
<nlm:affiliation>Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Genetics of Complex Traits, University of Exeter Medical School, Exeter</wicri:regionArea>
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<author>
<name sortKey="Martin, Richard M" sort="Martin, Richard M" uniqKey="Martin R" first="Richard M" last="Martin">Richard M. Martin</name>
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<nlm:affiliation>MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Integrative Epidemiology Unit at the University of Bristol, Bristol</wicri:regionArea>
<orgName type="university">Université de Bristol</orgName>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre du Sud-Ouest</region>
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</affiliation>
<affiliation wicri:level="4">
<nlm:affiliation>Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Population Health Sciences, Bristol Medical School, University of Bristol, Bristol</wicri:regionArea>
<orgName type="university">Université de Bristol</orgName>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
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<nlm:affiliation>National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol</wicri:regionArea>
<wicri:noRegion>Bristol</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Saxena, Richa" sort="Saxena, Richa" uniqKey="Saxena R" first="Richa" last="Saxena">Richa Saxena</name>
<affiliation wicri:level="2">
<nlm:affiliation>Centre for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Centre for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
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<affiliation wicri:level="2">
<nlm:affiliation>Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Program in Medical and Population Genetics, Broad Institute, Cambridge, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
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<nlm:affiliation>Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
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<nlm:affiliation>Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA</wicri:regionArea>
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<region type="state">Massachusetts</region>
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<name sortKey="Weedon, Michael N" sort="Weedon, Michael N" uniqKey="Weedon M" first="Michael N" last="Weedon">Michael N. Weedon</name>
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<nlm:affiliation>Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Genetics of Complex Traits, University of Exeter Medical School, Exeter</wicri:regionArea>
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<author>
<name sortKey="Lawlor, Debbie A" sort="Lawlor, Debbie A" uniqKey="Lawlor D" first="Debbie A" last="Lawlor">Debbie A. Lawlor</name>
<affiliation wicri:level="4">
<nlm:affiliation>MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Integrative Epidemiology Unit at the University of Bristol, Bristol</wicri:regionArea>
<orgName type="university">Université de Bristol</orgName>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre du Sud-Ouest</region>
</placeName>
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<nlm:affiliation>Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Population Health Sciences, Bristol Medical School, University of Bristol, Bristol</wicri:regionArea>
<orgName type="university">Université de Bristol</orgName>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre du Sud-Ouest</region>
</placeName>
</affiliation>
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<nlm:affiliation>National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol</wicri:regionArea>
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<name sortKey="Smith, George Davey" sort="Smith, George Davey" uniqKey="Smith G" first="George Davey" last="Smith">George Davey Smith</name>
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<nlm:affiliation>MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
<region type="country">Angleterre</region>
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<nlm:affiliation>Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.</nlm:affiliation>
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<settlement type="city">Bristol (Royaume-Uni)</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre du Sud-Ouest</region>
</placeName>
</affiliation>
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<nlm:affiliation>National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol</wicri:regionArea>
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<series>
<title level="j">BMJ (Clinical research ed.)</title>
<idno type="eISSN">1756-1833</idno>
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<date when="2019" type="published">2019</date>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Adult (MeSH)</term>
<term>Aged (MeSH)</term>
<term>Breast Neoplasms (epidemiology)</term>
<term>Breast Neoplasms (etiology)</term>
<term>Case-Control Studies (MeSH)</term>
<term>Circadian Rhythm (MeSH)</term>
<term>Comorbidity (MeSH)</term>
<term>Confounding Factors, Epidemiologic (MeSH)</term>
<term>Female (MeSH)</term>
<term>Genome-Wide Association Study (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Incidence (MeSH)</term>
<term>Mendelian Randomization Analysis (MeSH)</term>
<term>Middle Aged (MeSH)</term>
<term>Multivariate Analysis (MeSH)</term>
<term>Prospective Studies (MeSH)</term>
<term>Risk Factors (MeSH)</term>
<term>Sleep (MeSH)</term>
<term>Sleep Initiation and Maintenance Disorders (epidemiology)</term>
<term>Time Factors (MeSH)</term>
<term>United Kingdom (epidemiology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adulte (MeSH)</term>
<term>Adulte d'âge moyen (MeSH)</term>
<term>Analyse de randomisation mendélienne (MeSH)</term>
<term>Analyse multifactorielle (MeSH)</term>
<term>Comorbidité (MeSH)</term>
<term>Facteurs de risque (MeSH)</term>
<term>Facteurs temps (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Incidence (MeSH)</term>
<term>Royaume-Uni (épidémiologie)</term>
<term>Rythme circadien (MeSH)</term>
<term>Sommeil (MeSH)</term>
<term>Sujet âgé (MeSH)</term>
<term>Troubles de l'endormissement et du maintien du sommeil (épidémiologie)</term>
<term>Tumeurs du sein (épidémiologie)</term>
<term>Tumeurs du sein (étiologie)</term>
<term>Étude d'association pangénomique (MeSH)</term>
<term>Études cas-témoins (MeSH)</term>
<term>Études prospectives (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en">
<term>United Kingdom</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en">
<term>Breast Neoplasms</term>
<term>Sleep Initiation and Maintenance Disorders</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en">
<term>Breast Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr">
<term>Royaume-Uni</term>
<term>Troubles de l'endormissement et du maintien du sommeil</term>
<term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" qualifier="étiologie" xml:lang="fr">
<term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Case-Control Studies</term>
<term>Circadian Rhythm</term>
<term>Comorbidity</term>
<term>Confounding Factors, Epidemiologic</term>
<term>Female</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Incidence</term>
<term>Mendelian Randomization Analysis</term>
<term>Middle Aged</term>
<term>Multivariate Analysis</term>
<term>Prospective Studies</term>
<term>Risk Factors</term>
<term>Sleep</term>
<term>Time Factors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de randomisation mendélienne</term>
<term>Analyse multifactorielle</term>
<term>Comorbidité</term>
<term>Facteurs de risque</term>
<term>Facteurs temps</term>
<term>Femelle</term>
<term>Humains</term>
<term>Incidence</term>
<term>Rythme circadien</term>
<term>Sommeil</term>
<term>Sujet âgé</term>
<term>Étude d'association pangénomique</term>
<term>Études cas-témoins</term>
<term>Études prospectives</term>
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<div type="abstract" xml:lang="en">
<p>
<b>OBJECTIVE</b>
</p>
<p>To examine whether sleep traits have a causal effect on risk of breast cancer.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>DESIGN</b>
</p>
<p>Mendelian randomisation study.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>SETTING</b>
</p>
<p>UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>PARTICIPANTS</b>
</p>
<p>156 848 women in the multivariable regression and one sample mendelian randomisation (MR) analysis in UK Biobank (7784 with a breast cancer diagnosis) and 122 977 breast cancer cases and 105 974 controls from BCAC in the two sample MR analysis.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>EXPOSURES</b>
</p>
<p>Self reported chronotype (morning or evening preference), insomnia symptoms, and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>MAIN OUTCOME MEASURE</b>
</p>
<p>Breast cancer diagnosis.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>RESULTS</b>
</p>
<p>In multivariable regression analysis using UK Biobank data on breast cancer incidence, morning preference was inversely associated with breast cancer (hazard ratio 0.95, 95% confidence interval 0.93 to 0.98 per category increase), whereas there was little evidence for an association between sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated with sleep duration, and 57 SNPs associated with insomnia symptoms, one sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (0.85, 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two sample MR using data from BCAC supported findings for a protective effect of morning preference (inverse variance weighted odds ratio 0.88, 95% confidence interval 0.82 to 0.93 per category increase) and adverse effect of increased sleep duration (1.19, 1.02 to 1.39 per hour increase) on breast cancer risk (both oestrogen receptor positive and oestrogen receptor negative), whereas evidence for insomnia symptoms was inconsistent. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>CONCLUSIONS</b>
</p>
<p>Findings showed consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of increased sleep duration on breast cancer risk.</p>
</div>
</front>
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<Month>01</Month>
<Day>10</Day>
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<ISSN IssnType="Electronic">1756-1833</ISSN>
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<Volume>365</Volume>
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<Year>2019</Year>
<Month>Jun</Month>
<Day>26</Day>
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<ArticleTitle>Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study.</ArticleTitle>
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<AbstractText Label="DESIGN" NlmCategory="METHODS">Mendelian randomisation study.</AbstractText>
<AbstractText Label="SETTING" NlmCategory="METHODS">UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.</AbstractText>
<AbstractText Label="PARTICIPANTS" NlmCategory="METHODS">156 848 women in the multivariable regression and one sample mendelian randomisation (MR) analysis in UK Biobank (7784 with a breast cancer diagnosis) and 122 977 breast cancer cases and 105 974 controls from BCAC in the two sample MR analysis.</AbstractText>
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<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Findings showed consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of increased sleep duration on breast cancer risk.</AbstractText>
<CopyrightInformation>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</CopyrightInformation>
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<CoiStatement>Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf. MKR reports receiving research funding from Novo Nordisk, consultancy fees from Novo Nordisk and Roche Diabetes Care, and modest owning of shares in GlaxoSmithKline, outside the submitted work. DAL reports receiving research support from Medtronic and Roche Diagnostics for research outside the submitted work. All other authors declare no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.</CoiStatement>
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