Genome-Wide Association Study of Lung Adenocarcinoma in East Asia and Comparison With a European Population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

The Complexation of a CTV-Based Molecular Container to Tetra-alkyl Ammonium Salts

運用實驗室先前發展出來之ＣＴＶ為基礎的分子容器合成策略，合成以dibenzo-30-crown-10為架構之ＣＴＶ分子容器。將分子容器與適當之客體分子做錯合的研究，從NMR氫譜上可以看到明顯之化學位移改變，可推測我們的分子容器對此客體分子有錯合之作用。We have synthesized the cyclotirveratrylene molecular container based on dibenzo-30-crown-10 using the method we developed before. We studied the complex character between the molecular container and appropriate guest molecule. It showed that the chemical shift of the 1H-NMR spectra moved obviously. We supposed there were some interaction between our molecular container and the guest molecule.謝誌　..............................................................I文摘要　.........................................................III文摘要　.........................................................IV錄 ............................................................. V表　............................................................VII程　............................................................. X格　............................................................ XI、　導論　......................................................　1.1前言　.........................................................　1.2超分子化學的發展與冠醚的起源　.................................　3.3超分子系統　...................................................　7.3.1 主客化學 (Host -guest chemistry)　 ...........................　7.3.2 杯芳烴 (Calixarene）　....................................... 8.3.3 分子監獄 (Carcerand )　 ....................................　9.3.4 準車輪烷 (Psudortaxane)　 .................................　10.4 環三聚藜烴 ( Cyclotriveratrylene )　 ............................... 15.5 環三聚藜烴衍生物之應用　....................................... 17、　結果與討論　................................................　25.1研究動機　......................................................25.2目標分子的合成 .................................................27.3錯合測試　......................................................29、　結論　......................................................　39、　實驗部分　..................................................　40、　參考文獻　..................................................　47、　附錄　......................................................　5

Modify the Solubility and Reduction Potentials of C60 by Forming Its Highly Stable Hemicarceplexes

我們合成了一個可將 C60 封鎖於囚籠分子中的活門囚籠錯合物 (hemicarceplex)。此活門囚籠錯合物即使在大氣下被加熱至 523 K，持續 3 小時仍能維持其分子的完整性。實驗觀察到活門囚籠錯合物的溶解度相對於未鍵結的 C60 有大幅度的提升，且囚籠中的 C60 之還原電位亦因形成錯合物而有明顯的上升。利用有機金屬反應對活門囚籠錯合物加以 [(η5-C5Me5)RuII]+ 單元的修飾，可明顯提升此活門囚籠錯合物在 protic 溶劑 (MeOH 等) 的溶解度。A highly stable C60-incarcerated hemicarceplex, which can retain its molecular integrity after being heated up to 523 K in air for at least 3 h, was synthesized. The significant increase in the organic solubility and reductive potentials of its entrapped C60 unit was observed. Modification with [(η5-C5Me5)RuII]+ dramatically increased the solubility of this hemicarceplex into polar, protic solvents (e.g., MeOH).發表論文 ……………………………………..……………………………………...… i 摘要 …………………………………………..….………………………………….… ii 目錄 ……………………………………………….………………………………..… iii 圖目錄 ………………………………………………………………...……………… iv 表目錄 ………………………………………………………………….….…….…… vi 流程目錄 …………………………………………………………………..………… vii 第一章 ………………………………………………………………………………. 1 1.1 簡介 ……………………………………………………………………….. 2 1.1.1 富勒烯 (Fullerene) ………………………………………………… 2 1.1.2 環三聚藜烴 ( Cyclotriveratrylene ) ……………………………….. 8 1.1.3 分子囚籠 (Carcerand ) …………………………………………… 13 1.2 研究動機 ………………………………………………………………… 17 1.3 分子設計與活門囚籠錯合物之合成 …………………………………… 19 1.4 分子穩定性 ……………………………………………………………… 25 1.5 提升活門囚籠錯合物在極性溶劑中溶解度之研究 …………………… 28 1.6 結論 ……………………………………………………………………… 31 實驗部分 ………………………………...………………………………………… 32 參考文獻 ………………………………...………………………………………… 40 附錄 ……………………………………...………………………………………… 4

Hemicarceplexes Modify the Solubility and Reduction Potentials of C₆₀

A highly stable C₆₀-incarcerated hemicarceplex, which retains its molecular integrity after heating at 523 K in air for at least 3 h, significantly increases the solubility of C₆₀ in nonpolar solvents and increases the reduction potentials of the entrapped fullerene. Modification with [(η⁵-C₅Me₅)­Ru^II]⁺ dramatically increases the solubility of this hemicarceplex in polar, protic solvents (e.g., MeOH)

Tuberculosis infection and lung adenocarcinoma:Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.</p