Search for rare protein altering variants influencing susceptibility to multiple myeloma

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Title: Search for rare protein altering variants influencing susceptibility to multiple myeloma
Author(s): 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
Item Type: Journal Article
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.
Publication Date: 3-Mar-2017
Date of Acceptance: 28-Jan-2017
URI: http://hdl.handle.net/10044/1/48428
DOI: https://dx.doi.org/10.18632/oncotarget.15874
ISSN: 1949-2553
Publisher: Impact Journals
Start Page: 36203
End Page: 36210
Journal / Book Title: Oncotarget
Volume: 8
Issue: 22
Copyright Statement: © 2017 Scales et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: WT/104955/Z/14/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
multiple myeloma
inherited risk
exome sequencing
GENOME-WIDE ASSOCIATION
DNA-SEQUENCING DATA
RISK
PROLIFERATION
EXPRESSION
CARCINOMA
FRAMEWORK
exome sequencing
inherited risk
multiple myeloma
Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
multiple myeloma
inherited risk
exome sequencing
GENOME-WIDE ASSOCIATION
DNA-SEQUENCING DATA
RISK
PROLIFERATION
EXPRESSION
CARCINOMA
FRAMEWORK
Publication Status: Published
Open Access location: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=15874&path%5B%5D=50757
Appears in Collections:Faculty of Natural Sciences



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