Search for multiple myeloma risk factors using Mendelian randomization

Molly Went, Alex J. Cornish, Philip J. Law, Ben Kinnersley, Mark van Duin, Niels Weinhold, Asta Försti, Markus Hansson, Pieter Sonneveld, Hartmut Goldschmidt, Gareth J. Morgan, Kari Hemminki, Björn Nilsson, Martin Kaiser, Richard S. Houlston

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2172-2179
Number of pages8
JournalBlood Advances
Issue number10
Publication statusPublished - 2020

Subject classification (UKÄ)

  • Hematology
  • Cancer and Oncology
  • Medical Genetics


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