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Search for multiple myeloma risk factors using Mendelian randomization

Went, Molly ; Cornish, Alex J. ; Law, Philip J. ; Kinnersley, Ben ; van Duin, Mark ; Weinhold, Niels ; Försti, Asta LU ; Hansson, Markus LU orcid ; Sonneveld, Pieter and Goldschmidt, Hartmut , et al. (2020) In Blood Advances 4(10). p.2172-2179
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood Advances
volume
4
issue
10
pages
8 pages
publisher
American Society of Hematology
external identifiers
  • pmid:32433745
  • scopus:85086862492
ISSN
2473-9529
DOI
10.1182/bloodadvances.2020001502
language
English
LU publication?
yes
id
93755d20-1855-4593-8256-dd897f5512d8
date added to LUP
2020-07-10 09:53:10
date last changed
2024-04-17 12:33:33
@article{93755d20-1855-4593-8256-dd897f5512d8,
  abstract     = {{<p>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 10<sup>24</sup> 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 10<sup>23</sup>) with greater MM risk and v-3 fatty acids (P 5 5.4 3 10<sup>24</sup>) 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.</p>}},
  author       = {{Went, Molly and Cornish, Alex J. and Law, Philip J. and Kinnersley, Ben and van Duin, Mark and Weinhold, Niels and Försti, Asta and Hansson, Markus and Sonneveld, Pieter and Goldschmidt, Hartmut and Morgan, Gareth J. and Hemminki, Kari and Nilsson, Björn and Kaiser, Martin and Houlston, Richard S.}},
  issn         = {{2473-9529}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2172--2179}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood Advances}},
  title        = {{Search for multiple myeloma risk factors using Mendelian randomization}},
  url          = {{http://dx.doi.org/10.1182/bloodadvances.2020001502}},
  doi          = {{10.1182/bloodadvances.2020001502}},
  volume       = {{4}},
  year         = {{2020}},
}