Direct evidence for a polygenic etiology in familial multiple myeloma

Abstract

Key Points Although common risk alleles for multiple myeloma have been identified, their contribution to familial MM is unknown. We demonstrate an enrichment of common MM risk alleles in familial cases, providing the first direct evidence for a polygenic contribution.

Analysis of 153 115 patients with hematological malignancies refines the spectrum of familial risk

“…49 Indeed, although few published studies have investigated the role of such variation in MDS and AML, common genetic variants have already been shown to contribute significantly to the FRR of the other hematological malignancies. 36,43,44,89,90 Albeit preliminary, evidence for a shared susceptibility between different hematological malignancies consistent with our observations has been proposed from recent analyses of GWAS data. 91,92 A component of the FRR may also be explained by shared environmental risk factors, although the magnitude of their role in explaining familial aggregation has been debated.…”

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

“…A one-sided Student’s t -test was used to assess difference between groups. The genetic data have been previously described 5 , 60 with the familial MM cases having been identified by linkages of Swedish registry information.…”

Characterization of rare germline variants in familial multiple myeloma

“…In families of two affected individuals, polygenic risks would be more likely than in multiplex families of many affected individuals. In a previous study, evidence of enrichment of the common MM risk alleles among familial cases compared to sporadic cases or populationbased controls was reported 15 . Our search did not consider polygenic risk.…”