Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci

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Fältnamn	Indikatorer	Metadata
000		05160naa a2200853 4500
001		oai:DiVA.org:umu-116749
003		SwePub
008		160211s2016 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:132807806
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1167492 URI
024	7	a https://doi.org/10.1093/carcin/bgv1652 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1328078062 URI
040		a (SwePub)umud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Kachuri, Linda4 aut
245	1 0	a Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci
264		c 2015-11-20
264	1	b Oxford University Press (OUP),c 2016
338		a print2 rdacarrier
520		a Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000x) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73x10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64x10(-6)), rs112290073 (OR = 1.85, P = 1.27x10(-5)), rs138895564 (OR = 2.16, P = 2.06x10(-5); among young cases, OR = 3.77, P = 8.41x10(-4)). In addition, we found that rs139852726 (P = 1.44x10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84x10(-7)) and lung cancer (P = 2.37x10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
700	1	a Amos, Christopher I.4 aut
700	1	a Mckay, James D.4 aut
700	1	a Johansson, Mattiasu Umeå universitet,Enheten för biobanksforskning4 aut0 (Swepub:umu)masmas97
700	1	a Vineis, Paolo4 aut
700	1	a Bueno-de-Mesquita, H. Bas4 aut
700	1	a Boutron-Ruault, Marie-Christine4 aut
700	1	a Johansson, Mikaelu Umeå universitet,Institutionen för strålningsvetenskaper4 aut0 (Swepub:umu)mijo0025
700	1	a Quiros, J. Ramon4 aut
700	1	a Sieri, Sabina4 aut
700	1	a Travis, Ruth C.4 aut
700	1	a Weiderpass, Elisabeteu Karolinska Institutet4 aut
700	1	a Le Marchand, Loic4 aut
700	1	a Henderson, Brian E.4 aut
700	1	a Wilkens, Lynne4 aut
700	1	a Goodman, Gary E.4 aut
700	1	a Chen, Chu4 aut
700	1	a Doherty, Jennifer A.4 aut
700	1	a Christiani, David C.4 aut
700	1	a Wei, Yongyue4 aut
700	1	a Su, Li4 aut
700	1	a Tworoger, Shelley4 aut
700	1	a Zhang, Xuehong4 aut
700	1	a Kraft, Peter4 aut
700	1	a Zaridze, David4 aut
700	1	a Field, John K.4 aut
700	1	a Marcus, Michael W.4 aut
700	1	a Davies, Michael P. A.4 aut
700	1	a Hyde, Russell4 aut
700	1	a Caporaso, Neil E.4 aut
700	1	a Landi, Maria Teresa4 aut
700	1	a Severi, Gianluca4 aut
700	1	a Giles, Graham G.4 aut
700	1	a Liu, Geoffrey4 aut
700	1	a McLaughlin, John R.4 aut
700	1	a Li, Yafang4 aut
700	1	a Xiao, Xiangjun4 aut
700	1	a Fehringer, Gord4 aut
700	1	a Zong, Xuchen4 aut
700	1	a Denroche, Robert E.4 aut
700	1	a Zuzarte, Philip C.4 aut
700	1	a McPherson, John D.4 aut
700	1	a Brennan, Paul4 aut
700	1	a Hung, Rayjean J.4 aut
710	2	a Umeå universitetb Enheten för biobanksforskning4 org
773	0	t Carcinogenesisd : Oxford University Press (OUP)g 37:1, s. 96-105q 37:1<96-105x 0143-3334x 1460-2180
856	4	u https://academic.oup.com/carcin/article-pdf/37/1/96/17294239/bgv165.pdf
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-116749
856	4 8	u https://doi.org/10.1093/carcin/bgv165
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:132807806

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Av författaren/redakt...: Kachuri, Linda; Amos, Christophe ...; Mckay, James D.; Johansson, Matti ...; Vineis, Paolo; Bueno-de-Mesquit ...; visa fler...; Boutron-Ruault, ...; Johansson, Mikae ...; Quiros, J. Ramon; Sieri, Sabina; Travis, Ruth C.; Weiderpass, Elis ...; Le Marchand, Loi ...; Henderson, Brian ...; Wilkens, Lynne; Goodman, Gary E.; Chen, Chu; Doherty, Jennife ...; Christiani, Davi ...; Wei, Yongyue; Su, Li; Tworoger, Shelle ...; Zhang, Xuehong; Kraft, Peter; Zaridze, David; Field, John K.; Marcus, Michael ...; Davies, Michael ...; Hyde, Russell; Caporaso, Neil E ...; Landi, Maria Ter ...; Severi, Gianluca; Giles, Graham G.; Liu, Geoffrey; McLaughlin, John ...; Li, Yafang; Xiao, Xiangjun; Fehringer, Gord; Zong, Xuchen; Denroche, Robert ...; Zuzarte, Philip ...; McPherson, John ...; Brennan, Paul; Hung, Rayjean J.; visa färre...

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