Search for rare protein altering variants influencing susceptibility to multiple myeloma.
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Date
2017-05-30Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Multiple Myeloma
Genetic Predisposition to Disease
Kinesin
Risk
DNA Mutational Analysis
Mitosis
Gene Frequency
Genotype
Gene Dosage
Polymorphism, Single Nucleotide
Aged
Female
Male
Genetic Association Studies
High-Throughput Nucleotide Sequencing
Transcriptome
Exome
Research team
Cancer Genomics
Molecular & Population Genetics
Language
eng
Date accepted
2017-01-28
License start date
2017-05
Citation
Oncotarget, 2017, 8 (22), pp. 36203 - 36210
Publisher
IMPACT JOURNALS LLC