domingo, 27 de julio de 2014

Imputation and subset based association analys... [Hum Mol Genet. 2014] - PubMed - NCBI

Imputation and subset based association analys... [Hum Mol Genet. 2014] - PubMed - NCBI



 2014 Jul 15. pii: ddu363. [Epub ahead of print]

Imputation and subset based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

Wang Z1Zhu B2Zhang M2Parikh H2Jia J2Chung CC1Sampson JN2Hoskins JW2Hutchinson A1Burdette L1Ibrahim A2Hautman C1Raj PS2Abnet CC2Adjei AA3Ahlbom A4Albanes D2Allen NE5Ambrosone CB6Aldrich M7Amiano P8Amos C9Andersson U10Andriole G Jr11Andrulis IL12Arici C13,Arslan AA14Austin MA15Baris D2Barkauskas DA16Bassig BA17Beane Freeman LE2Berg CD18Berndt SI2Bertazzi PA19Biritwum RB3Black A2Blot W20Boeing H21Boffetta P22Bolton K23Boutron-Ruault MC24Bracci PM25Brennan P26Brinton LA2Brotzman M27Bueno-de-Mesquita HB28Buring JE29Butler MA30Cai Q7Cancel-Tassin G31Canzian F32Cao G33Caporaso NE2Carrato A34Carreon T30Carta A12Chang GC35Chang IS36Chang-Claude J32Che X37Chen CJ38Chen CY39Chen CH36Chen C40Chen KY41Chen YM42Chokkalingam AP43Chu LW44Clavel-Chapelon F45Colditz GA46Colt JS2Conti D16Cook MB2Cortessis VK16Crawford ED47Cussenot O48Davis FG49De Vivo I50Deng X1Ding T51Dinney CP52Di Stefano AL53Diver WR54Duell EJ55Elena JW56Fan JH57Feigelson HS58Feychting M4Figueroa JD2Flanagan AM59Fraumeni JF Jr2Freedman ND2Fridley BL60Fuchs CS61Gago-Dominguez M62Gallinger S63Gao YT64Gapstur SM54Garcia-Closas M65Garcia-Closas R66Gastier-Foster JM67Gaziano JM68Gerhard DS69Giffen CA70Giles GG71Gillanders EM72Giovannucci EL73Goggins M74Gokgoz N75Goldstein AM2Gonzalez C76Gorlick R77,Greene MH2Gross M78Grossman HB52Grubb R 3rd79Gu J80Guan P81Haiman CA82Hallmans G83Hankinson SE84Harris CC85Hartge P2,Hattinger C86Hayes RB87He Q81Helman L88Henderson BE82Henriksson R10Hoffman-Bolton J89Hohensee C90Holly EA25Hong YC91Hoover RN2Hosgood HD 3rd92Hsiao CF93Hsing AW94Hsiung CA95Hu N2Hu W2Hu Z96Huang MS97Hunter DJ98Inskip PD2Ito H99Jacobs EJ54Jacobs KB100Jenab M26Ji BT2Johansen C101Johansson M102Johnson A103Kaaks R32Kamat AM52Kamineni A104Karagas M9Khanna C88Khaw KT105,Kim C2Kim IS106Kim YH107Kim YC108Kim YT109Kang CH109Jung YJ109Kitahara CM2Klein AP110Klein R111Kogevinas M112Koh WP113Kohno T114Kolonel LN115Kooperberg C90Kratz CP116Krogh V117Kunitoh H118Kurtz RC111Kurucu N119Lan Q2Lathrop M120Lau CC121Lecanda F122,Lee KM123Lee MP88Le Marchand L115Lerner SP124Li D125Liao LM2Lim WY126Lin D127Lin J80Lindstrom S40Linet MS2Lissowska J128Liu J129,Ljungberg B130Lloreta J131Lu D132Ma J133Malats N134Mannisto S135Marina N136Mastrangelo G137Matsuo K138McGlynn KA2McKean-Cowdin R80,McNeill LH139McWilliams RR140Melin BS10Meltzer PS88Mensah JE3Miao X141Michaud DS142Mondul AM2Moore LE2Muir K143Niwa S27Olson SH144Orr N145Panico S146Park JY147Patel AV54Patino-Garcia A122Pavanello S137Peeters PH148Peplonska B149Peters U90Petersen GM140Picci P86Pike MC150Porru S13Prescott J50Pu X80Purdue MP2Qiao YL151Rajaraman P2Riboli E152Risch HA153Rodabough RJ90Rothman N2Ruder AM30Ryu JS154Sanson M53Schned A9Schumacher FR82Schwartz AG155Schwartz KL156Schwenn M157Scotlandi K86Seow A126Serra C158Serra M86Sesso HD29Severi G71Shen H96Shen M2Shete S159Shiraishi K114Shu XO7Siddiq A160Sierrasesumaga L122Sierri S161Sihoe AD162,Silverman DT2Simon M163Southey MC164Spector L165Spitz M166Stampfer M133Stattin P130Stern MC82Stevens VL54Stolzenberg-Solomon RZ2,Stram DO82Strom SS167Su WC168Sund M169Sung SW170Swerdlow A171Tan W127Tanaka H99Tang W2Tang ZZ51Tardon A172Tay E3Taylor PR2,Tettey Y3Thomas DM173Tirabosco R174Tjonneland A175Tobias GS2Toro JR2Travis RC5Trichopoulos D176Troisi R2Truelove A27Tsai YH177,Tucker MA2Tumino R178Van Den Berg D82Van Den Eeden SK179Vermeulen R180Vineis P181Visvanathan K89Vogel U182Wang C2Wang C37Wang J183Wang SS184Weiderpass E185Weinstein SJ2Wentzensen N2Wheeler W70White E90Wiencke JK186Wolk A187Wolpin BM61Wong MP188,Wrensch M186Wu C127Wu T141Wu X80Wu YL189Wunder JS11Xiang YB64Xu J190Yang HP2Yang PC97Yatabe Y191Ye Y80Yeboah ED3Yin Z81,Ying C126Yu CJ168Yu K2Yuan JM192Zanetti KA56Zeleniuch-Jacquotte A193Zheng W7Zhou B81Mirabello L2Savage SA2Kraft P194Chanock SJ1,Yeager M1Landi MT2Shi J2Chatterjee N2Amundadottir LT195.

Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

PMID:
 
25027329
 
[PubMed - as supplied by publisher]

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