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dc.contributor.authorGuo, Yen_US
dc.contributor.authorWarren Andersen, Sen_US
dc.contributor.authorShu, X-Oen_US
dc.contributor.authorMichailidou, Ken_US
dc.contributor.authorBolla, MKen_US
dc.contributor.authorWang, Qen_US
dc.contributor.authorGarcia-Closas, Men_US
dc.contributor.authorMilne, RLen_US
dc.contributor.authorSchmidt, MKen_US
dc.contributor.authorChang-Claude, Jen_US
dc.contributor.authorDunning, Aen_US
dc.contributor.authorBojesen, SEen_US
dc.contributor.authorAhsan, Hen_US
dc.contributor.authorAittomäki, Ken_US
dc.contributor.authorAndrulis, ILen_US
dc.contributor.authorAnton-Culver, Hen_US
dc.contributor.authorArndt, Ven_US
dc.contributor.authorBeckmann, MWen_US
dc.contributor.authorBeeghly-Fadiel, Aen_US
dc.contributor.authorBenitez, Jen_US
dc.contributor.authorBogdanova, NVen_US
dc.contributor.authorBonanni, Ben_US
dc.contributor.authorBørresen-Dale, A-Len_US
dc.contributor.authorBrand, Jen_US
dc.contributor.authorBrauch, Hen_US
dc.contributor.authorBrenner, Hen_US
dc.contributor.authorBrüning, Ten_US
dc.contributor.authorBurwinkel, Ben_US
dc.contributor.authorCasey, Gen_US
dc.contributor.authorChenevix-Trench, Gen_US
dc.contributor.authorCouch, FJen_US
dc.contributor.authorCox, Aen_US
dc.contributor.authorCross, SSen_US
dc.contributor.authorCzene, Ken_US
dc.contributor.authorDevilee, Pen_US
dc.contributor.authorDörk, Ten_US
dc.contributor.authorDumont, Men_US
dc.contributor.authorFasching, PAen_US
dc.contributor.authorFigueroa, Jen_US
dc.contributor.authorFlesch-Janys, Den_US
dc.contributor.authorFletcher, Oen_US
dc.contributor.authorFlyger, Hen_US
dc.contributor.authorFostira, Fen_US
dc.contributor.authorGammon, Men_US
dc.contributor.authorGiles, GGen_US
dc.contributor.authorGuénel, Pen_US
dc.contributor.authorHaiman, CAen_US
dc.contributor.authorHamann, Uen_US
dc.contributor.authorHooning, MJen_US
dc.contributor.authorHopper, JLen_US
dc.contributor.authorJakubowska, Aen_US
dc.contributor.authorJasmine, Fen_US
dc.contributor.authorJenkins, Men_US
dc.contributor.authorJohn, EMen_US
dc.contributor.authorJohnson, Nen_US
dc.contributor.authorJones, MEen_US
dc.contributor.authorKabisch, Men_US
dc.contributor.authorKibriya, Men_US
dc.contributor.authorKnight, JAen_US
dc.contributor.authorKoppert, LBen_US
dc.contributor.authorKosma, V-Men_US
dc.contributor.authorKristensen, Ven_US
dc.contributor.authorLe Marchand, Len_US
dc.contributor.authorLee, Een_US
dc.contributor.authorLi, Jen_US
dc.contributor.authorLindblom, Aen_US
dc.contributor.authorLuben, Ren_US
dc.contributor.authorLubinski, Jen_US
dc.contributor.authorMalone, KEen_US
dc.contributor.authorMannermaa, Aen_US
dc.contributor.authorMargolin, Sen_US
dc.contributor.authorMarme, Fen_US
dc.contributor.authorMcLean, Cen_US
dc.contributor.authorMeijers-Heijboer, Hen_US
dc.contributor.authorMeindl, Aen_US
dc.contributor.authorNeuhausen, SLen_US
dc.contributor.authorNevanlinna, Hen_US
dc.contributor.authorNeven, Pen_US
dc.contributor.authorOlson, JEen_US
dc.contributor.authorPerez, JIAen_US
dc.contributor.authorPerkins, Ben_US
dc.contributor.authorPeterlongo, Pen_US
dc.contributor.authorPhillips, K-Aen_US
dc.contributor.authorPylkäs, Ken_US
dc.contributor.authorRudolph, Aen_US
dc.contributor.authorSantella, Ren_US
dc.contributor.authorSawyer, EJen_US
dc.contributor.authorSchmutzler, RKen_US
dc.contributor.authorSeynaeve, Cen_US
dc.contributor.authorShah, Men_US
dc.contributor.authorShrubsole, MJen_US
dc.contributor.authorSouthey, MCen_US
dc.contributor.authorSwerdlow, AJen_US
dc.contributor.authorToland, AEen_US
dc.contributor.authorTomlinson, Ien_US
dc.contributor.authorTorres, Den_US
dc.contributor.authorTruong, Ten_US
dc.contributor.authorUrsin, Gen_US
dc.contributor.authorVan Der Luijt, RBen_US
dc.contributor.authorVerhoef, Sen_US
dc.contributor.authorWhittemore, ASen_US
dc.contributor.authorWinqvist, Ren_US
dc.contributor.authorZhao, Hen_US
dc.contributor.authorZhao, Sen_US
dc.contributor.authorHall, Pen_US
dc.contributor.authorSimard, Jen_US
dc.contributor.authorKraft, Pen_US
dc.contributor.authorPharoah, Pen_US
dc.contributor.authorHunter, Den_US
dc.contributor.authorEaston, DFen_US
dc.contributor.authorZheng, Wen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-01-17T11:02:53Z
dc.date.issued2016-08en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/27551723en_US
dc.identifierPMEDICINE-D-15-03646en_US
dc.identifier.citationPLoS Med, 2016, 13 (8), pp. e1002105 - ?en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3014
dc.identifier.eissn1549-1676en_US
dc.identifier.doi10.1371/journal.pmed.1002105en_US
dc.description.abstractBACKGROUND: Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. METHODS: We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases  =  46,325, controls  =  42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. RESULTS: In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR]  =  0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 × 10-10). The associations were similar for both premenopausal (OR   =   0.44, 95% CI:0.31-0.62, p  =  9.91 × 10-8) and postmenopausal breast cancer (OR  =  0.57, 95% CI: 0.46-0.71, p  =  1.88 × 10-8). This association was replicated in the data from the DRIVE consortium (OR  =  0.72, 95% CI: 0.60-0.84, p   =   1.64 × 10-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. CONCLUSIONS: BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.en_US
dc.format.extente1002105 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectBody Mass Indexen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectEuropean Continental Ancestry Groupen_US
dc.subjectFemaleen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectHumansen_US
dc.subjectMendelian Randomization Analysisen_US
dc.subjectMenopauseen_US
dc.subjectMiddle Ageden_US
dc.subjectModels, Statisticalen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectRisk Factorsen_US
dc.titleGenetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-06-24en_US
rioxxterms.versionofrecord10.1371/journal.pmed.1002105en_US
rioxxterms.licenseref.startdate2016-08en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfPLoS Meden_US
pubs.issue8en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genetic Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.publication-statusPublished onlineen_US
pubs.volume13en_US
pubs.embargo.termsNot knownen_US
icr.researchteamFunctional Genetic Epidemiologyen_US
icr.researchteamAetiological Epidemiologyen_US
dc.contributor.icrauthorJones, Michaelen_US
dc.contributor.icrauthorSwerdlow, Anthonyen_US
dc.contributor.icrauthorFletcher, Oliviaen_US


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