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000284938 0247_ $$2doi$$a10.1093/jncics/pkad088
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000284938 041__ $$aEnglish
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000284938 1001_ $$aNaderi, Elnaz$$b0
000284938 245__ $$aLarge-Scale Meta-GWAS Reveals Common Genetic Factors Linked to Radiation-Induced Acute Toxicities across Cancers.
000284938 260__ $$aOxford$$bOxford University Press$$c2023
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000284938 500__ $$a2023 Oct 31;7(6):pkad088
000284938 520__ $$aThis study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity (RIT) across four cancer types (prostate, head and neck, breast, and lung).A GWAS meta-analysis was performed using 19 cohorts including 12,042 patients. Acute standardized total average toxicity (rSTATacute) was modelled using a generalized linear regression model for additive effect of genetic variants adjusted for demographic and clinical covariates. LD score regression estimated shared SNP-based heritability of rSTATacute in all patients and for each cancer type.Shared SNP-based heritability of STATacute among all cancer types was estimated at 10% (se = 0.02), and was higher for prostate (17%, se = 0.07), head and neck (27%, se = 0.09), and breast (16%, se = 0.09) cancers. We identified 130 suggestive associated SNPs with rSTATacute (5.0x10-8<P-value<1.0x10-5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size -0.17; P-value=1.7x10-7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 x10-6, Pcorrected =0.079) as the top gene set associated with rSTATacute among all patients. In-silico gene expression analysis showed the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed Pcorrected=0.004; sun exposed Pcorrected=0.026).There is shared SNP-based heritability for acute RIT across and within individual cancer sites. Future meta-GWAS among large radiotherapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types.
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000284938 650_7 $$2Other$$aGWAS
000284938 650_7 $$2Other$$aRadiogenomics
000284938 650_7 $$2Other$$aSNP-based heritability
000284938 650_7 $$2Other$$aacute radiation-induced toxicity
000284938 7001_ $$aAguado-Barrera, Miguel E$$b1
000284938 7001_ $$aSchack, Line M H$$b2
000284938 7001_ $$aDorling, Leila$$b3
000284938 7001_ $$aRattay, Tim$$b4
000284938 7001_ $$aFachal, Laura$$b5
000284938 7001_ $$aSummersgill, Holly$$b6
000284938 7001_ $$aMartínez-Calvo, Laura$$b7
000284938 7001_ $$aWelsh, Ceilidh$$b8
000284938 7001_ $$aDudding, Tom$$b9
000284938 7001_ $$aOdding, Yasmin$$b10
000284938 7001_ $$aVarela-Pazos, Ana$$b11
000284938 7001_ $$aJena, Rajesh$$b12
000284938 7001_ $$aThomson, David J$$b13
000284938 7001_ $$aSteenbakkers, Roel J H M$$b14
000284938 7001_ $$aDennis, Joe$$b15
000284938 7001_ $$aLobato-Busto, Ramón$$b16
000284938 7001_ $$aAlsner, Jan$$b17
000284938 7001_ $$aNess, Andy$$b18
000284938 7001_ $$aNutting, Chris$$b19
000284938 7001_ $$aGómez-Caamaño, Antonio$$b20
000284938 7001_ $$aEriksen, Jesper G$$b21
000284938 7001_ $$aThomas, Steve J$$b22
000284938 7001_ $$aBates, Amy M$$b23
000284938 7001_ $$aWebb, Adam J$$b24
000284938 7001_ $$aChoudhury, Ananya$$b25
000284938 7001_ $$aRosenstein, Barry S$$b26
000284938 7001_ $$aTaboada-Valladares, Begona$$b27
000284938 7001_ $$aHerskind, Carsten$$b28
000284938 7001_ $$aAzria, David$$b29
000284938 7001_ $$aDearnaley, David P$$b30
000284938 7001_ $$ade Ruysscher, Dirk$$b31
000284938 7001_ $$aSperk, Elena$$b32
000284938 7001_ $$aHall, Emma$$b33
000284938 7001_ $$aStobart, Hilary$$b34
000284938 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b35$$udkfz
000284938 7001_ $$aDe Ruyck, Kim$$b36
000284938 7001_ $$aVeldeman, Liv$$b37
000284938 7001_ $$aAltabas, Manuel$$b38
000284938 7001_ $$aDe Santis, Maria Carmen$$b39
000284938 7001_ $$aFarcy-Jacquet, Marie-Pierre$$b40
000284938 7001_ $$aVeldwijk, Marlon R$$b41
000284938 7001_ $$aSydes, Matthew R$$b42
000284938 7001_ $$aParliament, Matthew$$b43
000284938 7001_ $$aUsmani, Nawaid$$b44
000284938 7001_ $$aBurnet, Neil G$$b45
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000284938 7001_ $$aSymonds, R Paul$$b47
000284938 7001_ $$aElliott, Rebecca M$$b48
000284938 7001_ $$aBultijnck, Renée$$b49
000284938 7001_ $$aGutiérrez-Enríquez, Sara$$b50
000284938 7001_ $$aMollà, Meritxell$$b51
000284938 7001_ $$aGulliford, Sarah L$$b52
000284938 7001_ $$aGreen, Sheryl$$b53
000284938 7001_ $$aRancati, Tiziana$$b54
000284938 7001_ $$aReyes, Victoria$$b55
000284938 7001_ $$aCarballo, Ana$$b56
000284938 7001_ $$aPeleteiro, Paula$$b57
000284938 7001_ $$aSosa-Fajardo, Paloma$$b58
000284938 7001_ $$aParker, Chris$$b59
000284938 7001_ $$aFonteyne, Valérie$$b60
000284938 7001_ $$aJohnson, Kerstie$$b61
000284938 7001_ $$aLambrecht, Maarten$$b62
000284938 7001_ $$aVanneste, Ben$$b63
000284938 7001_ $$aValdagni, Riccardo$$b64
000284938 7001_ $$aGiraldo, Alexandra$$b65
000284938 7001_ $$aRamos, Mónica$$b66
000284938 7001_ $$aDiergaarde, Brenda$$b67
000284938 7001_ $$aLiu, Geoffrey$$b68
000284938 7001_ $$aLeal, Suzanne M$$b69
000284938 7001_ $$aChua, Melvin L K$$b70
000284938 7001_ $$aPring, Miranda$$b71
000284938 7001_ $$aOvergaard, Jens$$b72
000284938 7001_ $$aCascallar-Caneda, Luis M$$b73
000284938 7001_ $$aDuprez, Fréderic$$b74
000284938 7001_ $$aTalbot, Christopher J$$b75
000284938 7001_ $$aBarnett, Gillian C$$b76
000284938 7001_ $$aDunning, Alison M$$b77
000284938 7001_ $$aVega, Ana$$b78
000284938 7001_ $$aAndreassen, Christian Nicolaj$$b79
000284938 7001_ $$aLangendijk, Johannes A$$b80
000284938 7001_ $$aWest, Catharine M L$$b81
000284938 7001_ $$aAlizadeh, Behrooz Z$$b82
000284938 7001_ $$aKerns, Sarah L$$b83
000284938 7001_ $$aConsortium, On the behalf of the Radiogenomics$$b84$$eCollaboration Author
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