演講者：陳孜圩  博士

　　　　國家衛生研究院

日　期：2023年11月08日（星期三）14:30

地　點：國立高雄大學理學院408室

講　題：Genome-wide and transcriptome-wide association studies of lung adenocarcinoma in East Asia

摘   要：

Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer, which accounts for 20% of all cancer deaths worldwide. In this talk, I will introduce our efforts in the etiology studies of LUAD, which may help propose prevention and treatment measures. Multiple genome-wide association studies (GWAS), performed in diverse populations or cross-ancestry populations, have identified dozens of significant susceptibility variants for LUAD. These risk variants account for only a small fraction of the familial risk in East Asian populations. A recent GWAS of LUAD of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Based on the GWAS summary statistics at over six million variants, we conducted transcriptome-wide association analyses (TWAS) using a Taiwanese lung expression quantitative trait loci (eQTL) dataset (n = 115) and identified two novel candidate genes, FADS1 at 11q12 and ELF5 at 11p13. These findings provide new insights into the etiology of LUAD in individuals from East Asian populations. Because genes with low expression heritability may still explain a substantial proportion of complex trait etiology, we need to explore all the gene expressions in eQTL studies. This suggests that enlarging the sample size of eQTL datasets may help to increase the number of predictable genes for TWAS. For this, we proposed a method to combine two eQTL datasets generated from different platforms. We evaluated the performance of the method by the number of eQTL harboring genes and predictable genes and illustrated the method by one dataset from Illumina BeadArray technology and another from Illumina RNA-seq technology.