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dc.contributor.authorWent, M
dc.contributor.authorCornish, AJ
dc.contributor.authorLaw, PJ
dc.contributor.authorKinnersley, B
dc.contributor.authorvan Duin, M
dc.contributor.authorWeinhold, N
dc.contributor.authorFörsti, A
dc.contributor.authorHansson, M
dc.contributor.authorSonneveld, P
dc.contributor.authorGoldschmidt, H
dc.contributor.authorMorgan, GJ
dc.contributor.authorHemminki, K
dc.contributor.authorNilsson, B
dc.contributor.authorKaiser, M
dc.contributor.authorHoulston, RS
dc.date.accessioned2020-07-08T10:39:30Z
dc.date.issued2020-05
dc.identifier.citationBlood advances, 2020, 4 (10), pp. 2172 - 2179
dc.identifier.issn2473-9529
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3825
dc.identifier.eissn2473-9537
dc.identifier.doi10.1182/bloodadvances.2020001502
dc.description.abstractThe etiology of multiple myeloma (MM) is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited in a Mendelian randomization (MR) phenome-wide association study (PheWAS) to search for factors influencing MM risk. We performed an MR-PheWAS analyzing 249 phenotypes, proxied by 10 225 genetic variants, and summary genetic data from a GWAS of 7717 MM cases and 29 304 controls. Odds ratios (ORs) per 1 standard deviation increase in each phenotype were estimated under an inverse variance weighted random effects model. A Bonferroni-corrected threshold of P = 2 × 10-4 was considered significant, whereas P < .05 was considered suggestive of an association. Although no significant associations with MM risk were observed among the 249 phenotypes, 28 phenotypes showed evidence suggestive of association, including increased levels of serum vitamin B6 and blood carnitine (P = 1.1 × 10-3) with greater MM risk and ω-3 fatty acids (P = 5.4 × 10-4) with reduced MM risk. A suggestive association between increased telomere length and reduced MM risk was also noted; however, this association was primarily driven by the previously identified risk variant rs10936599 at 3q26 (TERC). Although not statistically significant, increased body mass index was associated with increased risk (OR, 1.10; 95% confidence interval, 0.99-1.22), supporting findings from a previous meta-analysis of prospective observational studies. Our study did not provide evidence supporting any modifiable factors examined as having a major influence on MM risk; however, it provides insight into factors for which the evidence has previously been mixed.
dc.formatPrint
dc.format.extent2172 - 2179
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.titleSearch for multiple myeloma risk factors using Mendelian randomization.
dc.typeJournal Article
dcterms.dateAccepted2020-04-10
rioxxterms.versionofrecord10.1182/bloodadvances.2020001502
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBlood advances
pubs.issue10
pubs.notesNot known
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.publication-statusPublished
pubs.volume4
pubs.embargo.termsNot known
icr.researchteamCancer Genomicsen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorWent, Mollyen
dc.contributor.icrauthorKinnersley, Benjaminen
dc.contributor.icrauthorHoulston, Richarden
dc.contributor.icrauthorKaiser, Martinen
dc.contributor.icrauthorLaw, Philipen
dc.contributor.icrauthorCornish, Alexanderen


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