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Search for multiple myeloma risk factors using Mendelian randomization
M. Went, AJ. Cornish, PJ. Law, B. Kinnersley, M. van Duin, N. Weinhold, A. Försti, M. Hansson, P. Sonneveld, H. Goldschmidt, GJ. Morgan, K. Hemminki, B. Nilsson, M. Kaiser, RS. Houlston
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
C1298/A8362
Cancer Research UK - United Kingdom
Europe PubMed Central od 2016
ROAD: Directory of Open Access Scholarly Resources od 2016
Odkazy
PubMed
32433745
DOI
10.1182/bloodadvances.2020001502
Knihovny.cz E-zdroje
- MeSH
- celogenomová asociační studie * MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- mendelovská randomizace MeSH
- mnohočetný myelom * epidemiologie genetika MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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 = 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.
Biomedical Center Faculty of Medicine in Pilsen Charles University Prague Pilsen Czech Republic
Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands
Department of Internal Medicine 5 University of Heidelberg Heidelberg Germany
Division of Cancer Epidemiology DKFZ DKTK Heidelberg Germany
Division of Genetics and Epidemiology The Institute of Cancer Research London United Kingdom
Division of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg Germany
Division of Molecular Pathology The Institute of Cancer Research London United Kingdom
Division of Pediatric Neurooncology DKFZ DKTK Heidelberg Germany
Hematology Clinic Skåne University Hospital Lund Sweden
Hopp Children's Cancer Center Heidelberg Germany
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- $a 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 = 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.
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