Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

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dc.citation.issue1
dc.citation.volume15
dc.contributor.authorChen Z
dc.contributor.authorGuo X
dc.contributor.authorTao R
dc.contributor.authorHuyghe JR
dc.contributor.authorLaw PJ
dc.contributor.authorFernandez-Rozadilla C
dc.contributor.authorPing J
dc.contributor.authorJia G
dc.contributor.authorLong J
dc.contributor.authorLi C
dc.contributor.authorShen Q
dc.contributor.authorXie Y
dc.contributor.authorTimofeeva MN
dc.contributor.authorThomas M
dc.contributor.authorSchmit SL
dc.contributor.authorDíez-Obrero V
dc.contributor.authorDevall M
dc.contributor.authorMoratalla-Navarro F
dc.contributor.authorFernandez-Tajes J
dc.contributor.authorPalles C
dc.contributor.authorSherwood K
dc.contributor.authorBriggs SEW
dc.contributor.authorSvinti V
dc.contributor.authorDonnelly K
dc.contributor.authorFarrington SM
dc.contributor.authorBlackmur J
dc.contributor.authorVaughan-Shaw PG
dc.contributor.authorShu X-O
dc.contributor.authorLu Y
dc.contributor.authorBroderick P
dc.contributor.authorStudd J
dc.contributor.authorHarrison TA
dc.contributor.authorConti DV
dc.contributor.authorSchumacher FR
dc.contributor.authorMelas M
dc.contributor.authorRennert G
dc.contributor.authorObón-Santacana M
dc.contributor.authorMartín-Sánchez V
dc.contributor.authorOh JH
dc.contributor.authorKim J
dc.contributor.authorJee SH
dc.contributor.authorJung KJ
dc.contributor.authorKweon S-S
dc.contributor.authorShin M-H
dc.contributor.authorShin A
dc.contributor.authorAhn Y-O
dc.contributor.authorKim D-H
dc.contributor.authorOze I
dc.contributor.authorWen W
dc.contributor.authorMatsuo K
dc.contributor.authorMatsuda K
dc.contributor.authorTanikawa C
dc.contributor.authorRen Z
dc.contributor.authorGao Y-T
dc.contributor.authorJia W-H
dc.contributor.authorHopper JL
dc.contributor.authorJenkins MA
dc.contributor.authorWin AK
dc.contributor.authorPai RK
dc.contributor.authorFigueiredo JC
dc.contributor.authorHaile RW
dc.contributor.authorGallinger S
dc.contributor.authorWoods MO
dc.contributor.authorNewcomb PA
dc.contributor.authorDuggan D
dc.contributor.authorCheadle JP
dc.contributor.authorKaplan R
dc.contributor.authorKerr R
dc.contributor.authorKerr D
dc.contributor.authorKirac I
dc.contributor.authorBöhm J
dc.contributor.authorMecklin J-P
dc.contributor.authorJousilahti P
dc.contributor.authorKnekt P
dc.contributor.authorAaltonen LA
dc.contributor.authorRissanen H
dc.contributor.authorPukkala E
dc.contributor.authorEriksson JG
dc.contributor.authorCajuso T
dc.contributor.authorHänninen U
dc.contributor.authorKondelin J
dc.contributor.authorPalin K
dc.contributor.authorTanskanen T
dc.contributor.authorRenkonen-Sinisalo L
dc.contributor.authorMännistö S
dc.contributor.authorAlbanes D
dc.contributor.authorWeinstein SJ
dc.contributor.authorRuiz-Narvaez E
dc.contributor.authorPalmer JR
dc.contributor.authorBuchanan DD
dc.contributor.authorPlatz EA
dc.contributor.authorVisvanathan K
dc.contributor.authorUlrich CM
dc.contributor.authorSiegel E
dc.contributor.authorBrezina S
dc.contributor.authorGsur A
dc.contributor.authorCampbell PT
dc.contributor.authorChang-Claude J
dc.contributor.authorHoffmeister M
dc.contributor.authorBrenner H
dc.contributor.authorSlattery ML
dc.contributor.authorPotter JD
dc.contributor.authorTsilidis KK
dc.contributor.authorSchulze MB
dc.contributor.authorGunter MJ
dc.contributor.authorMurphy N
dc.contributor.authorCastells A
dc.contributor.authorCastellví-Bel S
dc.contributor.authorMoreira L
dc.contributor.authorArndt V
dc.contributor.authorShcherbina A
dc.contributor.authorBishop DT
dc.contributor.authorGiles GG
dc.contributor.authorSouthey MC
dc.contributor.authorIdos GE
dc.contributor.authorMcDonnell KJ
dc.contributor.authorAbu-Ful Z
dc.contributor.authorGreenson JK
dc.contributor.authorShulman K
dc.contributor.authorLejbkowicz F
dc.contributor.authorOffit K
dc.contributor.authorSu Y-R
dc.contributor.authorSteinfelder R
dc.contributor.authorKeku TO
dc.contributor.authorvan Guelpen B
dc.contributor.authorHudson TJ
dc.contributor.authorHampel H
dc.contributor.authorPearlman R
dc.contributor.authorBerndt SI
dc.contributor.authorHayes RB
dc.contributor.authorMartinez ME
dc.contributor.authorThomas SS
dc.contributor.authorPharoah PDP
dc.contributor.authorLarsson SC
dc.contributor.authorYen Y
dc.contributor.authorLenz H-J
dc.contributor.authorWhite E
dc.contributor.authorLi L
dc.contributor.authorDoheny KF
dc.contributor.authorPugh E
dc.contributor.authorShelford T
dc.contributor.authorChan AT
dc.contributor.authorCruz-Correa M
dc.contributor.authorLindblom A
dc.contributor.authorHunter DJ
dc.contributor.authorJoshi AD
dc.contributor.authorSchafmayer C
dc.contributor.authorScacheri PC
dc.contributor.authorKundaje A
dc.contributor.authorSchoen RE
dc.contributor.authorHampe J
dc.contributor.authorStadler ZK
dc.contributor.authorVodicka P
dc.contributor.authorVodickova L
dc.contributor.authorVymetalkova V
dc.contributor.authorEdlund CK
dc.contributor.authorGauderman WJ
dc.contributor.authorShibata D
dc.contributor.authorToland A
dc.contributor.authorMarkowitz S
dc.contributor.authorKim A
dc.contributor.authorChanock SJ
dc.contributor.authorvan Duijnhoven F
dc.contributor.authorFeskens EJM
dc.contributor.authorSakoda LC
dc.contributor.authorGago-Dominguez M
dc.contributor.authorWolk A
dc.contributor.authorPardini B
dc.contributor.authorFitzGerald LM
dc.contributor.authorLee SC
dc.contributor.authorOgino S
dc.contributor.authorBien SA
dc.contributor.authorKooperberg C
dc.contributor.authorLi CI
dc.contributor.authorLin Y
dc.contributor.authorPrentice R
dc.contributor.authorQu C
dc.contributor.authorBézieau S
dc.contributor.authorYamaji T
dc.contributor.authorSawada N
dc.contributor.authorIwasaki M
dc.contributor.authorLe Marchand L
dc.contributor.authorWu AH
dc.contributor.authorQu C
dc.contributor.authorMcNeil CE
dc.contributor.authorCoetzee G
dc.contributor.authorHayward C
dc.contributor.authorDeary IJ
dc.contributor.authorHarris SE
dc.contributor.authorTheodoratou E
dc.contributor.authorReid S
dc.contributor.authorWalker M
dc.contributor.authorOoi LY
dc.contributor.authorLau KS
dc.contributor.authorZhao H
dc.contributor.authorHsu L
dc.contributor.authorCai Q
dc.contributor.authorDunlop MG
dc.contributor.authorGruber SB
dc.contributor.authorHoulston RS
dc.contributor.authorMoreno V
dc.contributor.authorCasey G
dc.contributor.authorPeters U
dc.contributor.authorTomlinson I
dc.contributor.authorZheng W
dc.coverage.spatialEngland
dc.date.accessioned2024-05-09T01:36:57Z
dc.date.available2024-05-09T01:36:57Z
dc.date.issued2024-04-26
dc.description.abstractGenome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
dc.description.confidentialfalse
dc.format.pagination3557-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/38670944
dc.identifier.citationChen Z, Guo X, Tao R, Huyghe JR, Law PJ, Fernandez-Rozadilla C, Ping J, Jia G, Long J, Li C, Shen Q, Xie Y, Timofeeva MN, Thomas M, Schmit SL, Díez-Obrero V, Devall M, Moratalla-Navarro F, Fernandez-Tajes J, Palles C, Sherwood K, Briggs SEW, Svinti V, Donnelly K, Farrington SM, Blackmur J, Vaughan-Shaw PG, Shu X-O, Lu Y, Broderick P, Studd J, Harrison TA, Conti DV, Schumacher FR, Melas M, Rennert G, Obón-Santacana M, Martín-Sánchez V, Oh JH, Kim J, Jee SH, Jung KJ, Kweon S-S, Shin M-H, Shin A, Ahn Y-O, Kim D-H, Oze I, Wen W, Matsuo K, Matsuda K, Tanikawa C, Ren Z, Gao Y-T, Jia W-H, Hopper JL, Jenkins MA, Win AK, Pai RK, Figueiredo JC, Haile RW, Gallinger S, Woods MO, Newcomb PA, Duggan D, Cheadle JP, Kaplan R, Kerr R, Kerr D, Kirac I, Böhm J, Mecklin J-P, Jousilahti P, Knekt P, Aaltonen LA, Rissanen H, Pukkala E, Eriksson JG, Cajuso T, Hänninen U, Kondelin J, Palin K, Tanskanen T, Renkonen-Sinisalo L, Männistö S, Albanes D, Weinstein SJ, Ruiz-Narvaez E, Palmer JR, Buchanan DD, Platz EA, Visvanathan K, Ulrich CM, Siegel E, Brezina S, Gsur A, Campbell PT, Chang-Claude J, Hoffmeister M, Brenner H, Slattery ML, Potter JD, Tsilidis KK, Schulze MB, Gunter MJ, Murphy N, Castells A, Castellví-Bel S, Moreira L, Arndt V, Shcherbina A, Bishop DT, Giles GG, Southey MC, Idos GE, McDonnell KJ, Abu-Ful Z, Greenson JK, Shulman K, Lejbkowicz F, Offit K, Su Y-R, Steinfelder R, Keku TO, van Guelpen B, Hudson TJ, Hampel H, Pearlman R, Berndt SI, Hayes RB, Martinez ME, Thomas SS, Pharoah PDP, Larsson SC, Yen Y, Lenz H-J, White E, Li L, Doheny KF, Pugh E, Shelford T, Chan AT, Cruz-Correa M, Lindblom A, Hunter DJ, Joshi AD, Schafmayer C, Scacheri PC, Kundaje A, Schoen RE, Hampe J, Stadler ZK, Vodicka P, Vodickova L, Vymetalkova V, Edlund CK, Gauderman WJ, Shibata D, Toland A, Markowitz S, Kim A, Chanock SJ, van Duijnhoven F, Feskens EJM, Sakoda LC, Gago-Dominguez M, Wolk A, Pardini B, FitzGerald LM, Lee SC, Ogino S, Bien SA, Kooperberg C, Li CI, Lin Y, Prentice R, Qu C, Bézieau S, Yamaji T, Sawada N, Iwasaki M, Le Marchand L, Wu AH, Qu C, McNeil CE, Coetzee G, Hayward C, Deary IJ, Harris SE, Theodoratou E, Reid S, Walker M, Ooi LY, Lau KS, Zhao H, Hsu L, Cai Q, Dunlop MG, Gruber SB, Houlston RS, Moreno V, Casey G, Peters U, Tomlinson I, Zheng W. (2024). Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.. Nat Commun. 15. 1. (pp. 3557-).
dc.identifier.doi10.1038/s41467-024-47399-x
dc.identifier.eissn2041-1723
dc.identifier.elements-typejournal-article
dc.identifier.issn0028-0836
dc.identifier.number3557
dc.identifier.pii10.1038/s41467-024-47399-x
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/69532
dc.languageeng
dc.publisherSpringer Nature
dc.publisher.urihttps://www.nature.com/articles/s41467-024-47399-x
dc.relation.isPartOfNat Commun
dc.rights(c) 2024 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectGenome-Wide Association Study
dc.subjectAsian People
dc.subjectWhite People
dc.subjectPolymorphism, Single Nucleotide
dc.subjectQuantitative Trait Loci
dc.subjectExome Sequencing
dc.subjectCase-Control Studies
dc.subjectTranscriptome
dc.subjectChromosome Mapping
dc.subjectMale
dc.subjectFemale
dc.subjectEast Asian People
dc.titleFine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.
dc.typeJournal article
pubs.elements-id488723
pubs.organisational-groupCollege of Health
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