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Search for multiple myeloma risk factors using Mendelian randomization
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- Went, Molly (author)
- Institute of Cancer Research London
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- Cornish, Alex J. (author)
- Institute of Cancer Research London
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- Law, Philip J. (author)
- Institute of Cancer Research London
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- Kinnersley, Ben (author)
- Institute of Cancer Research London
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- van Duin, Mark (author)
- Erasmus University Medical Center
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- Weinhold, Niels (author)
- Heidelberg University
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- Försti, Asta (author)
- German Cancer Research Centre
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- Hansson, Markus (author)
- Lund University,Lunds universitet,Myelomgruppen,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Myeloma research group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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- Sonneveld, Pieter (author)
- Erasmus University Medical Center
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- Goldschmidt, Hartmut (author)
- National Centre of Tumor Diseases,Heidelberg University
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- Morgan, Gareth J. (author)
- NYU Langone
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- Hemminki, Kari (author)
- German Cancer Research Centre,Charles University in Prague
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- Nilsson, Björn (author)
- Lund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Broad Institute
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- Kaiser, Martin (author)
- Institute of Cancer Research London
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- Houlston, Richard S. (author)
- Institute of Cancer Research London
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(creator_code:org_t)
- 2020-05-20
- 2020
- English 8 s.
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:10, s. 2172-2179
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Abstract
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- The 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 5 2 3 1024 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 5 1.1 3 1023) with greater MM risk and v-3 fatty acids (P 5 5.4 3 1024) 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Went, Molly
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Cornish, Alex J.
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Law, Philip J.
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Kinnersley, Ben
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van Duin, Mark
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Weinhold, Niels
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show more...
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Försti, Asta
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Hansson, Markus
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Sonneveld, Piete ...
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Goldschmidt, Har ...
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Morgan, Gareth J ...
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Hemminki, Kari
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Nilsson, Björn
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Kaiser, Martin
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Houlston, Richar ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Blood Advances
- By the university
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Lund University