{"id":"https://openalex.org/W2144887897","doi":"https://doi.org/10.1093/jnci/djn380","title":"Intermediacy and Gene\u2013Environment Interaction: The Example of CHRNA5-A3 Region, Smoking, Nicotine Dependence, and Lung Cancer","display_name":"Intermediacy and Gene\u2013Environment Interaction: The Example of CHRNA5-A3 Region, Smoking, Nicotine Dependence, and Lung Cancer","publication_year":2008,"publication_date":"2008-10-29","ids":{"openalex":"https://openalex.org/W2144887897","doi":"https://doi.org/10.1093/jnci/djn380","mag":"2144887897","pmid":"https://pubmed.ncbi.nlm.nih.gov/18957674","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/2610344"},"language":"en","primary_location":{"id":"doi:10.1093/jnci/djn380","doi":"https://doi.org/10.1093/jnci/djn380","is_oa":true,"landing_page_url":"https://doi.org/10.1093/jnci/djn380","pdf_url":"https://academic.oup.com/jnci/article-pdf/100/21/1488/18074723/djn380.pdf","source":{"id":"https://openalex.org/S98010888","display_name":"JNCI Journal of the National Cancer Institute","issn_l":"0027-8874","issn":["0027-8874","1460-2105"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"JNCI: Journal of the National Cancer Institute","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://academic.oup.com/jnci/article-pdf/100/21/1488/18074723/djn380.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5000421571","display_name":"Sholom Wacholder","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]},{"id":"https://openalex.org/I4391012607","display_name":"Division of Cancer Epidemiology and Genetics","ror":"https://ror.org/00vkwep27","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884","https://openalex.org/I4391012607"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sholom Wacholder","raw_affiliation_strings":["Division of Cancer Epidemiology and Genetics , National Cancer Institute , Bethesda , MD 20892","National Institutes of Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Epidemiology and Genetics , National Cancer Institute , Bethesda , MD 20892","institution_ids":["https://openalex.org/I4210140884","https://openalex.org/I4391012607"]},{"raw_affiliation_string":"National Institutes of Health","institution_ids":["https://openalex.org/I1299303238"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015067632","display_name":"Nilanjan Chatterjee","orcid":"https://orcid.org/0000-0002-9060-008X","observed_orcids":["https://orcid.org/0000-0002-9060-008X","https://orcid.org/0000-0003-3213-3839","https://orcid.org/0000-0002-7932-0191"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]},{"id":"https://openalex.org/I4391012607","display_name":"Division of Cancer Epidemiology and Genetics","ror":"https://ror.org/00vkwep27","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884","https://openalex.org/I4391012607"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nilanjan Chatterjee","raw_affiliation_strings":["Division of Cancer Epidemiology and Genetics , National Cancer Institute , Bethesda , MD","National Institutes of Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Epidemiology and Genetics , National Cancer Institute , Bethesda , MD","institution_ids":["https://openalex.org/I4210140884","https://openalex.org/I4391012607"]},{"raw_affiliation_string":"National Institutes of Health","institution_ids":["https://openalex.org/I1299303238"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5019329822","display_name":"Neil E. Caporaso","orcid":"https://orcid.org/0000-0001-7562-4609","observed_orcids":["https://orcid.org/0000-0001-7562-4609"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]},{"id":"https://openalex.org/I4391012607","display_name":"Division of Cancer Epidemiology and Genetics","ror":"https://ror.org/00vkwep27","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884","https://openalex.org/I4391012607"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Neil Caporaso","raw_affiliation_strings":["Division of Cancer Epidemiology and Genetics , National Cancer Institute , Bethesda , MD","National Institutes of Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Epidemiology and Genetics , National Cancer Institute , Bethesda , MD","institution_ids":["https://openalex.org/I4210140884","https://openalex.org/I4391012607"]},{"raw_affiliation_string":"National Institutes of Health","institution_ids":["https://openalex.org/I1299303238"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":5436,"currency":"USD","value_usd":5436},"apc_paid":null,"fwci":2.091,"has_fulltext":true,"cited_by_count":22,"citation_normalized_percentile":{"value":0.87493404,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":98},"biblio":{"volume":"100","issue":"21","first_page":"1488","last_page":"1491"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.7720000147819519,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.7720000147819519,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10060","display_name":"Smoking Behavior and Cessation","score":0.2054000049829483,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.002300000051036477,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/smoking","display_name":"smoking","score":0.6119999885559082},{"id":"https://openalex.org/keywords/nicotine-dependence","display_name":"nicotine dependence","score":0.9940000176429749},{"id":"https://openalex.org/keywords/lung-cancer","display_name":"lung cancer","score":0.8550000190734863},{"id":"https://openalex.org/keywords/genetic-risk-factors","display_name":"genetic risk factors","score":0.4950000047683716},{"id":"https://openalex.org/keywords/genome-wide-association-study","display_name":"genome-wide association study","score":0.621999979019165},{"id":"https://openalex.org/keywords/candidate-gene-approach","display_name":"candidate gene approach","score":0.4429999887943268},{"id":"https://openalex.org/keywords/gene-environment-mediation","display_name":"gene-environment mediation","score":0.5059999823570251},{"id":"https://openalex.org/keywords/smoking-behavior","display_name":"smoking behavior","score":0.3779999911785126},{"id":"https://openalex.org/keywords/carcinogenesis","display_name":"carcinogenesis","score":0.5709999799728394}],"concepts":[{"id":"https://openalex.org/C106208931","wikidata":"https://www.wikidata.org/wiki/Q1098876","display_name":"Genome-wide association study","level":5,"score":0.5873547196388245},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5489367842674255},{"id":"https://openalex.org/C186413461","wikidata":"https://www.wikidata.org/wiki/Q744727","display_name":"Genetic association","level":5,"score":0.5055863857269287},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.4513019621372223},{"id":"https://openalex.org/C69991583","wikidata":"https://www.wikidata.org/wiki/Q1423575","display_name":"Candidate gene","level":3,"score":0.4213860332965851},{"id":"https://openalex.org/C81917197","wikidata":"https://www.wikidata.org/wiki/Q628760","display_name":"Selection (genetic algorithm)","level":2,"score":0.41900891065597534},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.4178364872932434},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4159150719642639},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.3873668909072876},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.1971641182899475},{"id":"https://openalex.org/C135763542","wikidata":"https://www.wikidata.org/wiki/Q106016","display_name":"Genotype","level":3,"score":0.18391677737236023},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.16778117418289185},{"id":"https://openalex.org/C153209595","wikidata":"https://www.wikidata.org/wiki/Q501128","display_name":"Single-nucleotide polymorphism","level":4,"score":0.11887416243553162},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.09157407283782959},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.08209928870201111}],"mesh":[{"descriptor_ui":"D002884","descriptor_name":"Chromosomes, Human, Pair 15","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008175","descriptor_name":"Lung Neoplasms","qualifier_ui":"Q000209","qualifier_name":"etiology","is_major_topic":true},{"descriptor_ui":"D008175","descriptor_name":"Lung Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D009419","descriptor_name":"Nerve Tissue Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D011978","descriptor_name":"Receptors, Nicotinic","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D012307","descriptor_name":"Risk Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012907","descriptor_name":"Smoking","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D012907","descriptor_name":"Smoking","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D014029","descriptor_name":"Tobacco Use Disorder","qualifier_ui":"Q000150","qualifier_name":"complications","is_major_topic":false},{"descriptor_ui":"D014029","descriptor_name":"Tobacco Use Disorder","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D014644","descriptor_name":"Genetic Variation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D018570","descriptor_name":"Risk Assessment","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020022","descriptor_name":"Genetic Predisposition to Disease","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1093/jnci/djn380","doi":"https://doi.org/10.1093/jnci/djn380","is_oa":true,"landing_page_url":"https://doi.org/10.1093/jnci/djn380","pdf_url":"https://academic.oup.com/jnci/article-pdf/100/21/1488/18074723/djn380.pdf","source":{"id":"https://openalex.org/S98010888","display_name":"JNCI Journal of the National Cancer Institute","issn_l":"0027-8874","issn":["0027-8874","1460-2105"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"JNCI: Journal of the National Cancer Institute","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:2610344","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2610344","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"J Natl Cancer Inst","raw_type":"Text"},{"id":"pmid:18957674","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/18957674","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the National Cancer Institute","raw_type":"Comment"},{"id":"pmh:oai:open-archive.highwire.org:jnci:djn380v1","doi":null,"is_oa":false,"landing_page_url":"http://jnci.oxfordjournals.org/cgi/content/short/djn380v1","pdf_url":null,"source":{"id":"https://openalex.org/S4406923041","display_name":"HighWire Press Open Archive","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"TEXT"}],"best_oa_location":{"id":"doi:10.1093/jnci/djn380","doi":"https://doi.org/10.1093/jnci/djn380","is_oa":true,"landing_page_url":"https://doi.org/10.1093/jnci/djn380","pdf_url":"https://academic.oup.com/jnci/article-pdf/100/21/1488/18074723/djn380.pdf","source":{"id":"https://openalex.org/S98010888","display_name":"JNCI Journal of the National Cancer Institute","issn_l":"0027-8874","issn":["0027-8874","1460-2105"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"JNCI: Journal of the National Cancer Institute","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9922999739646912,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1242182657","display_name":"Methods for Epidemiology Studies","funder_award_id":"Z01CP010181","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2144887897.pdf","grobid_xml":"https://content.openalex.org/works/W2144887897.grobid-xml"},"referenced_works_count":49,"referenced_works":["https://openalex.org/W1031069717","https://openalex.org/W1257486597","https://openalex.org/W1511621596","https://openalex.org/W1883365293","https://openalex.org/W1965179808","https://openalex.org/W1970086516","https://openalex.org/W1971048436","https://openalex.org/W1972020976","https://openalex.org/W1977546001","https://openalex.org/W1995946306","https://openalex.org/W1998641738","https://openalex.org/W2002267074","https://openalex.org/W2007782096","https://openalex.org/W2009187570","https://openalex.org/W2020584313","https://openalex.org/W2024100487","https://openalex.org/W2034705696","https://openalex.org/W2035924724","https://openalex.org/W2044452743","https://openalex.org/W2047200356","https://openalex.org/W2049719667","https://openalex.org/W2062594082","https://openalex.org/W2074400792","https://openalex.org/W2083291438","https://openalex.org/W2087050944","https://openalex.org/W2093357561","https://openalex.org/W2101983393","https://openalex.org/W2102945991","https://openalex.org/W2110886382","https://openalex.org/W2112271873","https://openalex.org/W2113782542","https://openalex.org/W2115321131","https://openalex.org/W2118082971","https://openalex.org/W2118320202","https://openalex.org/W2120240963","https://openalex.org/W2125386601","https://openalex.org/W2126928020","https://openalex.org/W2144947515","https://openalex.org/W2155949904","https://openalex.org/W2157524492","https://openalex.org/W2157752701","https://openalex.org/W2160610058","https://openalex.org/W2169919802","https://openalex.org/W2187328923","https://openalex.org/W4240211860","https://openalex.org/W4285719527","https://openalex.org/W4294553991","https://openalex.org/W4388361680","https://openalex.org/W6674105709"],"related_works":["https://openalex.org/W7096075876","https://openalex.org/W2144947515","https://openalex.org/W2142349883","https://openalex.org/W2079675254","https://openalex.org/W3138169952","https://openalex.org/W34972455","https://openalex.org/W2168969220","https://openalex.org/W1672055544","https://openalex.org/W2119228827","https://openalex.org/W1487799282"],"abstract_inverted_index":{"During":[0],"the":[1,27,91,183,210,220,234,237,269,273,300,306,317,321,374,388,406,415,418,421,424,435,440,466,470,487,490,499,507,510,521,532,535,556,565,584,598,643,680,732,752,756,810,822,833,851,880,900,910,947,964,982,988,991,999,1044,1048,1058,1114,1129,1173,1191,1233,1344,1385,1394,1437,1457,1462,1469,1478,1508,1529,1544,1548,1551,1561],"\u201ccandidate":[2],"gene":[3,272,1154],"era,\u201d":[4],"many":[5,89],"studies":[6,36,57,79,181,260,313,325,512,768,1535],"with":[7,250,285,338,364,444,527,659,709,883,995,1014,1060,1069,1203],"a":[8,14,20,39,65,100,110,129,134,341,356,393,461,610,688,710,722,837,936,977,1018,1085,1094,1103,1133,1153,1156,1194,1257,1276,1443],"small":[9,15,252,286,611],"number":[10,16,22,66],"of":[11,17,23,29,32,67,72,90,106,118,132,143,185,212,236,261,271,279,296,299,303,308,314,316,326,344,378,417,423,437,442,493,509,520,534,537,574,583,646,666,669,677,755,784,809,836,850,874,879,923,935,960,966,968,990,1020,1053,1057,1081,1102,1132,1135,1162,1235,1259,1282,1388,1393,1397,1416,1481,1515,1533,1546,1550,1575,1579,1590],"cases":[12],"investigated":[13],"variants":[18,95,222,239,249,284,335,912,986,1209],"in":[19,64,187,246,282,305,430,465,564,590,687,749,761,789,814,856,877,886,908,914,987,1017,1072,1108,1152,1170,1242,1299,1310,1321,1468,1497,1521],"limited":[21],"genes":[24,1236],"chosen":[25],"on":[26,384,495,580,586,613,630,713,726,794,801,839,853,916,1028,1105,1117,1123,1140,1147,1402,1484,1572],"basis":[28],"partial":[30],"knowledge":[31,488],"their":[33,224,602,1539,1558],"function.":[34,225],"These":[35,1449],"established":[37],"only":[38,167,650,834],"few":[40],"genetic":[41,94,192,334,357,471,1314,1325],"risk":[42,71,278,377,433,573,876,889,1287,1514],"factors":[43,890,1241,1288,1309,1320],"for":[44,114,138,190,268,355,555,609,627,656,705,721,751,758,826,891,894,1149,1210,1464],"cancer":[45,263,281,328,346,380,399,432,855,885,1032,1071,1107,1142,1243,1517,1564],"(":[46,74,124,148,161,177,204,329,447,502,513,541,547,633,692,700,742,763,769,817,829,868,903,927,1033,1063,1074,1212,1279,1302,1331,1368,1380,1419,1428],"1":[47,1221,1523],")":[48,331,451,515,549,694,746,765,819,870,1067,1076,1281,1333,1376,1382,1423],"and":[49,103,145,151,196,254,288,293,319,411,473,498,539,572,594,623,671,682,684,695,697,766,776,797,820,893,913,933,997,1030,1068,1237,1346,1377,1390,1424,1446,1461,1513,1518,1531,1556,1584,1592],"other":[50,660,1061,1186,1224,1519],"diseases.":[51],"Remarkably,":[52],"recent":[53],"genome-wide":[54,115],"association":[55,144,213,441,658,678],"(GWA)":[56],"have":[58,230,1167,1554],"produced":[59],"strong":[60,607],"evidence":[61,608,655,873],"that":[62,240,523,561,821,946,1097,1113,1159,1175,1188,1487,1496],"variation":[63,1315,1326],"genomic":[68],"regions":[69],"affects":[70,408,568,1160],"disease":[73,297,365,840,1118,1317,1328],"2":[75],").":[76,179,206,771,831,905,929,1306],"Successful":[77],"GWA":[78,180,259,312,324,342,511,603,978,1534],"most":[80,242],"often":[81],"used":[82,153],"an":[83,265,456,628,657,792,1398,1403,1408,1441,1447,1482,1485,1492],"agnostic":[84,1526],"approach":[85,1527],"to":[86,99,232,244,360,397,553,729,735,860,958,1042,1125,1145,1185,1190,1218,1291,1316,1327,1362,1455,1476,1538],"interrogating":[87],"as":[88,96,157,601,616,640,805,1084,1357,1359],"more":[92,723,920,1007,1505,1585],"common":[93],"feasible":[97],"(up":[98],"million":[101],"now)":[102],"large":[104],"numbers":[105],"cases.":[107],"They":[108,207,605,1340],"adopted":[109],"de":[111],"facto":[112],"criterion":[113],"statistical":[116,154,1386,1582],"significance":[117],"P":[119],"values":[120],"below":[121],"10":[122,636],"\u22127":[123],"3":[125],"),":[126,150,163,506,543,639,702,1037,1434],"thus":[127],"guaranteeing":[128],"low":[130,140,255,289],"chance":[131],"reporting":[133],"false":[135],"positive":[136],"even":[137,962],"quite":[139],"prior":[141],"probabilities":[142],"weak":[146,651],"effects":[147,235,253,287,383,582],"4":[149],"they":[152,199,227],"methods,":[155],"such":[156,1499],"principal":[158],"components":[159,1164],"analysis":[160,578,902,1532],"5":[162],"which":[164,368,1284],"protects":[165],"not":[166,229,276,1040,1078,1090,1111,1265,1296,1489],"against":[168,173],"population":[169,777],"stratification":[170],"but":[171,366,649,716,1262],"also":[172,1144,1165,1452],"poor":[174],"control":[175,595],"selection":[176],"6":[178],"are":[182,241,264,824,918,1011,1039,1228],"culmination":[184],"advances":[186],"laboratory":[188,775],"methodologies":[189],"detecting":[191],"variation,":[193],"genomics,":[194],"statistics,":[195],"informatics,":[197],"yet":[198],"leave":[200],"important":[201,921],"scientific":[202],"gaps":[203],"7":[205],"can":[208,217,898,1341,1350,1435,1451],"establish":[209,1079],"presence":[211],"but,":[214],"by":[215,618,642,791,807,953,1120,1200],"themselves,":[216],"identify":[218,245,332],"neither":[219],"causal":[221,467,1311,1322,1395,1500],"nor":[223],"Currently,":[226],"do":[228],"power":[231],"capture":[233],"same":[238,599,1000],"difficult":[243],"family":[247],"studies:":[248],"very":[251],"minor":[256,290],"allele":[257,291],"frequencies.":[258],"lung":[262,280,327,345,379,398,431,479,528,575,714,802,854,884,895,1031,1070,1106,1141,1516],"instructive":[266],"model":[267],"study":[270,343,979],"variant":[274,358,375,389,407,472,562,585,838,852,881,937,984,1010,1104,1115,1196],"should":[275,846],"affect":[277,478,1198,1266],"those":[283,857],"frequencies":[292],"behavioral":[294,1238,1593],"determinants":[295],"because":[298,453],"dominant":[301],"role":[302,422,436,492,1234],"smoking":[304,348,385,402,412,454,496,500,570,588,614,661,673,785,892,917,951,996,1182],"etiology":[307],"this":[309],"disease.":[310,339],"Like":[311],"cancers":[315,686,699,727,1062],"breast":[318],"prostate,":[320],"first":[322],"three":[323,353],"8\u201310":[330,514,770,1034],"several":[333,1223],"strongly":[336,362],"associated":[337,363,526,882,994,1012],"But":[340],"without":[347,400,703,858],"information":[349,1571],"cannot":[350,980],"distinguish":[351,1336],"among":[352,1337,1440],"possibilities":[354,484],"found":[359],"be":[361,847,1216,1351,1453],"about":[367,489,1232],"nothing":[369],"was":[370,525],"previously":[371],"known:":[372],"1)":[373],"increases":[376],"solely":[381,1119],"through":[382,392,842,1269,1407,1491],"behavior;":[386,403],"2)":[387],"induces":[390],"carcinogenesis":[391,410,480],"molecular":[394,1591],"mechanism":[395],"relevant":[396],"affecting":[401],"or":[404,427,463,652,942,985,1002,1004,1006,1183,1205,1239,1400,1472],"3)":[405],"both":[409,483,569,780],"behavior.":[413],"Indeed,":[414],"essence":[416],"controversy":[419],"over":[420],"chromosome":[425,1562],"15q24/25.1":[426,443,476,494,566,1029],"CHRNA5-A3":[428],"region":[429,567,989,1019,1059],"is":[434,455,707,841,1099,1177,1271,1275,1295,1405,1488,1536],"smoking:":[438],"Does":[439,475],"nicotine":[445,631,737,795,843],"dependence":[446,632],"11":[448,503],",":[449,504,635,637,744,1035,1065,1304,1370,1372,1374,1421,1430,1432],"12":[450,505],"arise":[452],"intermediate":[457,1308,1319,1409,1445],"factor,":[458],"sometimes":[459],"called":[460],"mediator":[462],"endophenotype,":[464],"path":[468],"between":[469,679,1510],"disease?":[474],"itself":[477,1256],"directly?":[481],"Are":[482],"correct?":[485],"With":[486],"possible":[491,1444],"behavior":[497,571,1199],"data":[501,552,778],"authors":[508],"offer":[516],"differing":[517],"etiologic":[518],"interpretations":[519],"finding":[522],"15q24/25":[524],"cancer.":[529,576],"Now,":[530],"following":[531],"spirit":[533],"advice":[536],"Chanock":[538],"Hunter":[540],"13":[542],"Spitz":[544,762,865],"et":[545,866],"al.":[546,867],"14":[548,693,764,869,1036,1066,1075],"use":[550,1578],"new":[551],"argue":[554],"third":[557],"choice":[558],"mentioned":[559],"above,":[560],"rs1051370":[563],"Their":[577],"focuses":[579],"direct":[581],"measured":[587,617,641],"phenotypes":[589],"approximately":[591],"3600":[592],"case":[593,690,1278],"subjects":[596],"\u201cfrom":[597],"source":[600],"population.\u201d":[604],"find":[606],"effect":[612,629,712,725,793,800,835,849,1101,1122,1131,1169,1179,1396,1480],"intensity,":[615],"cigarettes":[619,969],"smoked":[620,970],"per":[621,971],"day,":[622],"provide":[624,1504],"further":[625,719],"support":[626,720],"9":[634],"15":[638],"Fagerstrom":[644],"Test":[645],"Nicotine":[647],"Dependence,":[648],"no":[653,718,848,872,1100,1168,1178],"supporting":[654],"phenotypes:":[662],"age":[663],"at":[664,787],"initiation":[665],"smoking,":[667,670,706,1136,1512],"duration":[668],"sustained":[672],"cessation.":[674],"The":[675,1051,1525],"lack":[676,1052,1080],"locus":[681],"bladder":[683],"renal":[685],"combined":[689],"set":[691],"head":[696],"neck":[698],"8":[701,743,1064],"adjustment":[704,1148],"consistent":[708],"specific":[711,983],"carcinogenesis,":[715],"provides":[717],"general":[724],"related":[728,1217],"tobacco.":[730],"Overall,":[731],"receptor's":[733],"ability":[734],"bind":[736,1189],"and,":[738],"possibly,":[739],"downstream":[740],"carcinogens":[741,828,1187],"16":[745],"may":[747,938,1334],"account":[748],"part":[750,790],"seeming":[753],"inconsistency":[754],"results":[757],"various":[759],"endpoints":[760],"earlier":[767],"For":[772,930,1560],"example,":[773,1247,1465],"some":[774],"suggest":[779],"central":[781],"(an":[782,799],"impact":[783],"mediated":[786,1406,1490],"least":[788],"dependency)":[796],"peripheral":[798],"carcinogenesis),":[803],"mechanisms":[804,1046],"evidenced":[806],"expression":[808],"nicotinic":[811],"acetylcholine":[812],"receptors":[813,823],"bronchial":[815],"cells":[816],"17":[818],"ligands":[825],"tobacco-specific":[827],"18":[830],"If":[832],"dependence,":[844],"there":[845,1098,1176,1227],"exposure":[859,1184,1399,1483],"smoking.":[861,1150],"In":[862,1245],"never":[863],"smokers,":[864],"saw":[871],"increased":[875],"carriers":[878,932],"smokers.":[887],"Unmeasured":[888],"cancer,":[896],"however,":[897],"distort":[899],"stratified":[901,1471],"19":[904,1369,1429],"Measurement":[906],"errors":[907],"identifying":[909],"functional":[911],"reports":[915,965],"perhaps":[919,957,1580,1587],"sources":[922],"bias":[924],"than":[925,1215],"confounding":[926],"20":[928],"instance,":[931],"noncarriers":[934],"metabolize":[939],"tobacco":[940,1163],"differently":[941],"behave":[943],"differently,":[944],"so":[945],"carcinogenic":[948],"dose":[949],"from":[950,1180,1313,1324,1353],"varies":[952],"carrier":[954],"status":[955],"due":[956],"depth":[959],"inhalation,":[961],"if":[963],"history":[967],"day":[972],"were":[973],"perfectly":[974],"accurate.":[975],"Also,":[976],"determine":[981],"tagging":[992],"SNP":[993,1001],"whether":[998,1389],"SNPs,":[1003],"one":[1005],"additional":[1008],"proximal":[1009],"directly":[1013],"disease,":[1015,1293],"especially":[1016],"high":[1021],"LD":[1022],"like":[1023,1137],"15q24/25.":[1024],"Despite":[1025],"impressive":[1026],"work":[1027],"we":[1038,1127,1542,1553],"close":[1041],"understanding":[1043],"precise":[1045,1458],"underlying":[1047],"genotypic":[1049],"association.":[1050,1092],"statistically":[1054,1086],"significant":[1055,1087],"associations":[1056,1552],"nonsmokers":[1073,1109],"does":[1077,1089,1110,1264],"association,":[1082,1565],"just":[1083],"result":[1088],"prove":[1091],"Even":[1093],"convincing":[1095],"demonstration":[1096],"imply":[1112],"acts":[1116],"its":[1121],"addiction":[1124],"smoking;":[1126],"expect":[1128],"noncausal":[1130],"consequence":[1134],"tobacco-stained":[1138],"teeth,":[1139],"would":[1143],"disappear":[1146],"Variants":[1151],"encoding":[1155],"metabolic":[1157,1195],"activity":[1158],"carcinogenicity":[1161],"will":[1166,1503,1568],"nonsmokers,":[1171],"under":[1172],"assumption":[1174],"passive":[1181],"receptors.":[1192],"Or":[1193],"might":[1197],"providing":[1201],"smokers":[1202],"pleasant":[1204],"unpleasant":[1206],"feedback\u2014like":[1207],"ALDH2":[1208],"alcohol":[1211],"21":[1213],")\u2014rather":[1214],"addiction.":[1219],"Table":[1220,1522],"lists":[1222],"examples":[1225,1520],"where":[1226,1249],"similar":[1229],"fundamental":[1230],"questions":[1231],"endogenous":[1240],"etiology.":[1244],"each":[1246],"intermediacy,":[1248],"factor":[1250,1254],"A":[1251,1263],"greatly":[1252],"influences":[1253],"B,":[1255,1270],"cause":[1258,1292],"outcome":[1260,1404,1486],"C,":[1261],"C":[1267],"except":[1268],"plausible.":[1272],"Although":[1273],"intermediacy":[1274],"special":[1277],"22":[1280,1371,1431],"interaction,":[1283],"addresses":[1285],"how":[1286,1391],"act":[1289],"together":[1290],"it":[1294],"always":[1297],"considered":[1298],"theoretical":[1300],"discussions":[1301],"23":[1303],"24":[1305],"Plausible":[1307,1318],"pathways":[1312,1323],"Statistical":[1329],"approaches":[1330],"25\u201328":[1332],"help":[1335,1342],"potential":[1338],"mechanisms.":[1339,1594],"articulate":[1343],"assumptions":[1345,1459],"define":[1347],"precisely":[1348],"what":[1349],"estimated":[1352],"standard":[1354,1470],"multivariate":[1355,1473],"analyses":[1356],"well":[1358],"alternative":[1360],"methods":[1361,1475],"address":[1363],"these":[1364],"questions.":[1365],"Both":[1366],"epidemiological":[1367],"28":[1373],"29":[1375],"clinical":[1378],"trial":[1379],"30":[1381],"literature":[1383],"discuss":[1384],"problem":[1387],"much":[1392],"treatment":[1401],"variable.":[1410],"Causal":[1411],"modeling":[1412,1501],"frameworks,":[1413],"including":[1414],"theory":[1415],"counterfactual":[1417],"outcomes":[1418],"31":[1420],"32":[1422],"directed":[1425],"acyclic":[1426],"graphs":[1427],"33":[1433],"examine":[1436],"complex":[1438],"interplay":[1439],"exposure,":[1442],"outcome.":[1448],"models":[1450],"useful":[1454],"understand":[1456],"needed":[1460],"pitfalls,":[1463],"unmeasured":[1466],"confounders,":[1467],"regression":[1474],"measure":[1477],"\u201cdirect\u201d":[1479],"intermediate.":[1493],"We":[1494],"anticipate":[1495],"future":[1498],"framework":[1502],"insight":[1506],"into":[1507],"interrelationship":[1509],"15q,":[1511],".":[1524],"underpinning":[1528],"design":[1530],"integral":[1537],"success.":[1540],"Now":[1541],"face":[1543],"challenge":[1545],"unraveling":[1547],"meaning":[1549],"discovered":[1555],"leveraging":[1557],"findings.":[1559],"15\u2013smoking\u2013lung":[1563],"inter-disciplinary":[1566],"teams":[1567],"require":[1569],"high-quality":[1570],"environmental":[1573],"causes":[1574],"disease;":[1576],"careful":[1577],"unfamiliar":[1581],"methods;":[1583],"gritty,":[1586],"hypothesis-based":[1588],"investigation":[1589]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2014,"cited_by_count":2},{"year":2013,"cited_by_count":3},{"year":2012,"cited_by_count":4}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}