PubMed:25937444 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/25937444","sourcedb":"PubMed","sourceid":"25937444","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/25937444","text":"Low-frequency coding variants at 6p21.33 and 20q11.21 are associated with lung cancer risk in Chinese populations.\nGenome-wide association studies have successfully identified a subset of common variants associated with lung cancer risk. However, these variants explain only a fraction of lung cancer heritability. It has been proposed that low-frequency or rare variants might have strong effects and contribute to the missing heritability. To assess the role of low-frequency or rare variants in lung cancer development, we analyzed exome chips representing 1,348 lung cancer subjects and 1,998 control subjects during the discovery stage and subsequently evaluated promising associations in an additional 4,699 affected subjects and 4,915 control subjects during the replication stages. Single-variant and gene-based analyses were carried out for coding variants with a minor allele frequency less than 0.05. We identified three low-frequency missense variants in BAT2 (rs9469031, c.1544C\u003eT [p.Pro515Leu]; odds ratio [OR] = 0.55, p = 1.28 × 10(-10)), FKBPL (rs200847762, c.410C\u003eT [p.Pro137Leu]; OR = 0.25, p = 9.79 × 10(-12)), and BPIFB1 (rs6141383, c.850G\u003eA [p.Val284Met]; OR = 1.72, p = 1.79 × 10(-7)); these variants were associated with lung cancer risk. rs9469031 in BAT2 and rs6141383 in BPIFB1 were also associated with the age of onset of lung cancer (p = 0.001 and 0.006, respectively). BAT2 and FKBPL at 6p21.33 and BPIFB1 at 20q11.21 were differentially expressed in lung tumors and paired normal tissues. Gene-based analysis revealed that FKBPL, in which two independent variants were identified, might account for the association with lung cancer risk at 6p21.33. Our results highlight the important role low-frequency variants play in lung cancer susceptibility and indicate that candidate genes at 6p21.33 and 20q11.21 are potentially biologically relevant to lung carcinogenesis.","tracks":[{"project":"PubTator4TogoVar","denotations":[{"id":"25937444_0","span":{"begin":995,"end":1006},"obj":"ProteinMutation"},{"id":"25937444_1","span":{"begin":1084,"end":1095},"obj":"ProteinMutation"},{"id":"25937444_2","span":{"begin":1163,"end":1174},"obj":"ProteinMutation"}],"attributes":[{"id":"25937444_0_ProteinMutation","pred":"proteinmutation","subj":"25937444_0","obj":"rs9469031"},{"id":"25937444_1_ProteinMutation","pred":"proteinmutation","subj":"25937444_1","obj":"rs200847762"},{"id":"25937444_2_ProteinMutation","pred":"proteinmutation","subj":"25937444_2","obj":"rs6141383"},{"subj":"25937444_0","pred":"source","obj":"PubTator4TogoVar"},{"subj":"25937444_1","pred":"source","obj":"PubTator4TogoVar"},{"subj":"25937444_2","pred":"source","obj":"PubTator4TogoVar"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":220,"end":231},"obj":"HP_0100526"},{"id":"T2","span":{"begin":225,"end":231},"obj":"HP_0002664"},{"id":"T3","span":{"begin":289,"end":300},"obj":"HP_0100526"},{"id":"T4","span":{"begin":294,"end":300},"obj":"HP_0002664"},{"id":"T5","span":{"begin":498,"end":509},"obj":"HP_0100526"},{"id":"T6","span":{"begin":503,"end":509},"obj":"HP_0002664"},{"id":"T7","span":{"begin":566,"end":577},"obj":"HP_0100526"},{"id":"T8","span":{"begin":571,"end":577},"obj":"HP_0002664"},{"id":"T9","span":{"begin":1244,"end":1255},"obj":"HP_0100526"},{"id":"T10","span":{"begin":1249,"end":1255},"obj":"HP_0002664"},{"id":"T11","span":{"begin":1350,"end":1361},"obj":"HP_0100526"},{"id":"T12","span":{"begin":1355,"end":1361},"obj":"HP_0002664"},{"id":"T13","span":{"begin":1481,"end":1492},"obj":"HP_0100526"},{"id":"T14","span":{"begin":1486,"end":1492},"obj":"HP_0002664"},{"id":"T15","span":{"begin":1651,"end":1662},"obj":"HP_0100526"},{"id":"T16","span":{"begin":1656,"end":1662},"obj":"HP_0002664"},{"id":"T17","span":{"begin":1752,"end":1763},"obj":"HP_0100526"},{"id":"T18","span":{"begin":1757,"end":1763},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"},{"subj":"T4","pred":"source","obj":"PubmedHPO"},{"subj":"T5","pred":"source","obj":"PubmedHPO"},{"subj":"T6","pred":"source","obj":"PubmedHPO"},{"subj":"T7","pred":"source","obj":"PubmedHPO"},{"subj":"T8","pred":"source","obj":"PubmedHPO"},{"subj":"T9","pred":"source","obj":"PubmedHPO"},{"subj":"T10","pred":"source","obj":"PubmedHPO"},{"subj":"T11","pred":"source","obj":"PubmedHPO"},{"subj":"T12","pred":"source","obj":"PubmedHPO"},{"subj":"T13","pred":"source","obj":"PubmedHPO"},{"subj":"T14","pred":"source","obj":"PubmedHPO"},{"subj":"T15","pred":"source","obj":"PubmedHPO"},{"subj":"T16","pred":"source","obj":"PubmedHPO"},{"subj":"T17","pred":"source","obj":"PubmedHPO"},{"subj":"T18","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET5_variant_disease","denotations":[{"id":"25937444-6#61#70#geners9469031","span":{"begin":973,"end":982},"obj":"geners9469031"},{"id":"25937444-6#83#94#geners9469031","span":{"begin":995,"end":1006},"obj":"geners9469031"},{"id":"25937444-6#162#170#geners200847762","span":{"begin":1074,"end":1082},"obj":"geners200847762"},{"id":"25937444-6#372#381#geners6141383","span":{"begin":1284,"end":1293},"obj":"geners6141383"},{"id":"25937444-6#350#359#geners9469031","span":{"begin":1262,"end":1271},"obj":"geners9469031"},{"id":"25937444-6#241#249#geners6141383","span":{"begin":1153,"end":1161},"obj":"geners6141383"},{"id":"25937444-6#72#81#geners9469031","span":{"begin":984,"end":993},"obj":"geners9469031"},{"id":"25937444-6#230#239#geners6141383","span":{"begin":1142,"end":1151},"obj":"geners6141383"},{"id":"25937444-6#149#160#geners200847762","span":{"begin":1061,"end":1072},"obj":"geners200847762"},{"id":"25937444-6#172#183#geners200847762","span":{"begin":1084,"end":1095},"obj":"geners200847762"},{"id":"25937444-6#251#262#geners6141383","span":{"begin":1163,"end":1174},"obj":"geners6141383"},{"id":"25937444-6#251#262#geners528285841","span":{"begin":1163,"end":1174},"obj":"geners528285841"},{"id":"25937444-6#251#262#geners6141383","span":{"begin":1163,"end":1174},"obj":"geners6141383"},{"id":"25937444-6#251#262#geners528285841","span":{"begin":1163,"end":1174},"obj":"geners528285841"},{"id":"25937444-6#332#343#diseaseC0242379","span":{"begin":1244,"end":1255},"obj":"diseaseC0242379"},{"id":"25937444-6#332#343#diseaseC0684249","span":{"begin":1244,"end":1255},"obj":"diseaseC0684249"},{"id":"25937444-6#332#343#diseaseC1306460","span":{"begin":1244,"end":1255},"obj":"diseaseC1306460"},{"id":"25937444-6#438#449#diseaseC0242379","span":{"begin":1350,"end":1361},"obj":"diseaseC0242379"},{"id":"25937444-6#438#449#diseaseC0684249","span":{"begin":1350,"end":1361},"obj":"diseaseC0684249"},{"id":"25937444-6#438#449#diseaseC1306460","span":{"begin":1350,"end":1361},"obj":"diseaseC1306460"},{"id":"25937444-6#332#343#diseaseC0242379","span":{"begin":1244,"end":1255},"obj":"diseaseC02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