Search for multiple myeloma risk factors using Mendelian randomization.

Area of Science:

• Genetics
• Epidemiology
• Oncology

Background:

• The causes of multiple myeloma (MM) remain largely unknown.
• Genome-wide association studies (GWASs) provide valuable genetic data for exploring disease etiology.
• Mendelian randomization (MR) and phenome-wide association studies (PheWAS) can identify potential risk factors.

Purpose of the Study:

• To investigate potential factors influencing multiple myeloma (MM) risk.
• To leverage summary data from GWASs in an MR-PheWAS approach.
• To analyze associations between 249 phenotypes and MM risk.

Main Methods:

• Performed a Mendelian randomization phenome-wide association study (MR-PheWAS).
• Analyzed 249 phenotypes using 10,225 genetic variants.
• Utilized GWAS summary data from 7,717 MM cases and 29,304 controls.
• Employed inverse variance weighted random effects models to estimate odds ratios (ORs).

Main Results:

• No statistically significant associations between the 249 phenotypes and MM risk were identified.
• Twenty-eight phenotypes showed suggestive associations with MM risk (P < .05).
• Increased serum vitamin B6 and blood carnitine levels were suggestively associated with greater MM risk.
• Increased omega-3 fatty acids were suggestively associated with reduced MM risk.
• A suggestive inverse association was noted for telomere length, largely driven by a known TERC variant.
• Increased body mass index showed a non-significant trend towards increased MM risk.

Conclusions:

• The study did not identify strong evidence for major modifiable risk factors for multiple myeloma (MM) among the phenotypes examined.
• Suggestive associations warrant further investigation, particularly for vitamin B6, carnitine, and omega-3 fatty acids.
• Findings offer insights into factors with previously mixed evidence regarding their role in MM risk.