Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Biology, University of Pisa, Pisa, Italy.
Eur J Hum Genet. 2022 Apr;30(4):474-479. doi: 10.1038/s41431-021-00986-8. Epub 2021 Nov 30.
There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53-4.69, p = 3.55 × 10 for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34-4.33, p = 1.62 × 10 for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population.
有大量的流行病学证据表明，多发性骨髓瘤（MM）的风险具有坚实的遗传背景。全基因组关联研究（GWAS）已经确定了 23 个风险位点，这些位点有助于 MM 的遗传易感性，但个体的外显率较低。通过组合多基因风险评分（PRS）中的 SNPs 是提高其有用性的一种可能方法。使用来自国际多发性骨髓瘤研究（IMMEnSE）联盟的 2361 例 MM 病例和 1415 例对照，我们计算了加权和非加权 PRS。我们观察到与 MM 风险的关联，最高五分位数与最低五分位数相比，加权评分的 OR=3.44，95%CI2.53-4.69，p=3.55×10；非加权评分的 OR=3.18，95%CI2.1-34-4.33，p=1.62×10。我们发现了一个由 23 个 SNP 生成的 PRS 与 MM 风险之间具有令人信服的关联。我们的工作为先前发现的 MM 风险变异及其组合成 PRS 提供了额外的验证，这是将遗传学用于一般人群风险分层的第一步。
