Search for rare protein altering variants influencing susceptibility to multiple myeloma.
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Authors
Scales, M
Chubb, D
Dobbins, SE
Johnson, DC
Li, N
Sternberg, MJ
Weinhold, N
Stein, C
Jackson, G
Davies, FE
Walker, BA
Wardell, CP
Houlston, RS
Morgan, GJ
Chubb, D
Dobbins, SE
Johnson, DC
Li, N
Sternberg, MJ
Weinhold, N
Stein, C
Jackson, G
Davies, FE
Walker, BA
Wardell, CP
Houlston, RS
Morgan, GJ
Document Type
Journal Article
Date
2017-05-30
Date Accepted
2017-01-28
Abstract
The genetic basis underlying the inherited risk of developing multiple myeloma (MM) is largely unknown. To examine the impact of rare protein altering variants on the risk of developing MM we analyzed high-coverage exome sequencing data on 513 MM cases and 1,569 healthy controls, performing both single variant and gene burden tests. We did not identify any recurrent coding low-frequency alleles (1-5%) with moderate effect that were statistically associated with MM. In a gene burden analysis we did however identify a promising relationship between variation in the marrow kinetochore microtubule stromal gene KIF18A, which plays a role in control mitotic chromosome positioning dynamics, and risk of MM (P =3.6x10-6). Further analysis showed KIF18A displays a distinct pattern of expression across molecular subgroups of MM as well as being associated with patient survival. Our results inform future study design and provide a resource for contextualizing the impact of candidate MM susceptibility genes.
Citation
Oncotarget, 2017, 8 (22), pp. 36203 - 36210
Source Title
Publisher
IMPACT JOURNALS LLC
ISSN
1949-2553
eISSN
1949-2553
Collections
Research Team
Cancer Genomics
Molecular & Population Genetics
Molecular & Population Genetics