Direct evidence for a polygenic etiology in familial multiple myeloma.

Halvarsson BM, Wihlborg AK, Ali M, Lemonakis K, Johnsson E, Niroula A, Cibulskis C, Weinhold N, Försti A, Alici E, Langer C, Pfreundschuh M, Goldschmidt H, Mellqvist UH, Turesson I, Waage A, Hemminki K, Golub T, Nahi H, Gullberg U, Hansson M, Nilsson B

Blood Adv 1 (10) 619-623 [2017-04-11; online 2017-04-07]

Although common risk alleles for multiple myeloma (MM) were recently identified, their contribution to familial MM is unknown. Analyzing 38 familial cases identified primarily by linking Swedish nationwide registries, we demonstrate an enrichment of common MM risk alleles in familial compared with 1530 sporadic cases (P = 4.8 × 10-2 and 6.0 × 10-2, respectively, for 2 different polygenic risk scores) and 10 171 population-based controls (P = 1.5 × 10-4 and 1.3 × 10-4, respectively). Using mixture modeling, we estimate that about one-third of familial cases result from such enrichments. Our results provide the first direct evidence for a polygenic etiology in a familial hematologic malignancy.

Abhishek Niroula

DDLS Fellow

PubMed 29296704

DOI 10.1182/bloodadvances.2016003111

Crossref 10.1182/bloodadvances.2016003111

pmc: PMC5728350
pii: 2016/003111

Publications 9.5.0