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| 1 | Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma显示文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments. | Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen | 2021 | Frontiers of Medicine2021，15，2： | 3 |
| 2 | Serum zinc correlates with parent-and teacher-rated inattention in children with attention-deficit/hyperactivity disorder显示文摘 | Arnold LE Bozzolo H Hollway J | 2005 | Child Adolesc Psychopharmacol2005，15，4： | 1 |
| 3 | A review of neurofeedback treatment for pediatric ADHD 显示文摘 | Loflhouse N Arnold LE Hersch S | 2012 | J AttenDisord2012，16，5： | 1 |
| 4 | Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled crossover pilot trial显示文摘 | Arnold LE Aman MG Cook AM | 2006 | Journal of Child & Adolescent Psychopharmacology2006，45，： | 1 |
| 5 | Review of the results of the ARO multicenter study显示文摘 | Arnold P Schüle B Schroeder-Boersch H | 1998 | Orthopade1998，27，6： | 1 |
| 6 | Serum zinc correlates with parent- and teacher- rated inattention in children with attention-deficit/hyperactivity disorder 显示文摘 | Arnold LE Bozzolo H Hollway J | 2005 | J Child Adolesc Psychopharmacol2005，15，4： | 1 |
| 7 | Zinc for attention-defi-cit/hyperactivity disorder:placebo-controlled double-blind pilot trial alone and combined with amphetamine显示文摘 | Arnold LE Disilvestro RA Bozzolo D | 2011 | J Child Adolesc Psycho-pharmacol2011，21，1： | 1 |
| 8 | Medication treatment strategies in the MTA Study: relevance to clinicians and researchers显示文摘 | Greenhill LL Abikoff HB Arnold LE | 1996 | J Am Acad Child Adolesc Psychiatry1996，35，10： | 1 |
| 9 | Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure显示文摘 | Ramirez CE Okamoto LE Arnold AC | 2014 | Hypertension2014，64，6： | 1 |
| 10 | Anxiety as a predictor and outcome variable in the multimodal treatment study of children with ADHD显示文摘 | March JS Swanson JM Arnold LE | 2000 | J Abnorm Child Psychol2000，28，6： | 1 |
| 11 | Identification and characterization of a spinal muscular atrophy-determining gene显示文摘 | Suzie Lefebvre Lydie Bürglen Sophie Reboullet Olivier Clermont Philippe Burlet Louis Viollet Bernard Benichou Corinne Cruaud Philippe Millasseau Massimo Zeviani Denis Le Paslier Jean Frézal Daniel Cohen Jean Weissenbach Arnold Munnich Judith Melki | 1995 | Cell1995，，1： | 1 |
| 12 | Attraction of the parasitic mite Varroa to the drone larvae of honey bees by simple aliphatic esters 显示文摘 | LE CONTE Y ARNOLD G TROILER J | 1989 | Scince1989，245，： | 1 |
| 13 | Temporal pheromonal and kairomonal secretion in the brood of honeybees显示文摘 | TROUILLER J ARNOLD GL LE CONTE Y | 1991 | Naturwissenschaften1991，78，： | 1 |
| 14 | Semiochemicals basis of the infestion of honeybee brood by Varroa jacobsoni显示文摘 | TROUILLER J ARNOLD GL LE CONTE Y | 1992 | Chemical Ecology1992，11，： | 1 |
| 15 | A clinical review of outcomes of the muhimodal treatment study of children with attention-deficit/hyperactivity disorder (MTA)显示文摘 | Murray DW Arnold LE Swanson J Wells K Burns K Jensen P | 2008 | Curr Psychiatry Rep2008，10，5： | 1 |
| 16 | Serum ferritin and amphetamine response in youth with attention-deficit/hyperactivity disorder显示文摘 | Calarge C Farmer C DiSilvestro R Arnold LE | 2010 | J Child Adolesc Psychopharmacol2010，20，6： | 1 |
| 17 | Attraction of the Parasitic mite Varroa to the Drone Larvae of Honey Bees by Simple Aliphatic Esters显示文摘 | LE CONTE Y ARNOLD G TROUILER J | 1989 | Science1989，，245： | 1 |
| 18 | Atomoxetine for hyperactivity in autism spectrum disorders : placebo-controlled crossover pilot trial 显示文摘 | Arnold LE Aman MG Cook AM | 2006 | J Am Acad Child Adolesc Psychiatry2006，45，10： | 1 |
| 19 | Attraction of the parasitic mite Varroa to the drone larvae of honey bees by simple aliphatic esters 显示文摘 | LE CONTE Y ARNOLD G TROILER J | 1989 | Scince1989，，25： | 1 |
| 20 | Temporal Pheromonal and Kairomonal Secretion in the Brood of Honeybees显示文摘 | TROILER J ARNOLD G LE CONTE Y | 1991 | Naturwissenschaften1991，，78： | 1 |
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