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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Sci+Rep
2015 ; 5
(ä): 10442
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A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk
variants for colorectal cancer
#MMPMID25990418
Al-Tassan NA
; Whiffin N
; Hosking FJ
; Palles C
; Farrington SM
; Dobbins SE
; Harris R
; Gorman M
; Tenesa A
; Meyer BF
; Wakil SM
; Kinnersley B
; Campbell H
; Martin L
; Smith CG
; Idziaszczyk S
; Barclay E
; Maughan TS
; Kaplan R
; Kerr R
; Kerr D
; Buchanan DD
; Win AK
; Hopper J
; Jenkins M
; Lindor NM
; Newcomb PA
; Gallinger S
; Conti D
; Schumacher F
; Casey G
; Dunlop MG
; Tomlinson IP
; Cheadle JP
; Houlston RS
Sci Rep
2015[May]; 5
(ä): 10442
PMID25990418
show ga
Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified
23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate
additional risk loci are yet to be discovered. To identify novel CRC
susceptibility loci, we conducted a new GWAS and performed a meta-analysis with
five published GWAS (totalling 7,577 cases and 9,979 controls of European
ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined
analysis identified new, significant associations with CRC at 1p36.2 marked by
rs72647484 (minor allele frequency [MAF]?=?0.09) near CDC42 and WNT4
(P?=?1.21?×?10(-8), odds ratio [OR]?=?1.21 ) and at 16q24.1 marked by rs16941835
(MAF?=?0.21, P?=?5.06?×?10(-8); OR?=?1.15) within the long non-coding RNA
(lncRNA) RP11-58A18.1 and ~500?kb from the nearest coding gene FOXL1.
Additionally we identified a promising association at 10p13 with rs10904849
intronic to CUBN (MAF?=?0.32, P?=?7.01?×?10(-8); OR?=?1.14). These findings
provide further insights into the genetic and biological basis of inherited
genetic susceptibility to CRC. Additionally, our analysis further demonstrates
that imputation can be used to exploit GWAS data to identify novel
disease-causing variants.