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

Y: Newly established monoclonal antibodies for immunological detection of H5N1 influenza virus

SUMMARY: The H5N1 subtype of the highly pathogenic (HP) avian influenza virus has been recognized for its ability to cause serious pandemics among humans. In the present study, new monoclonal antibodies (mAbs) against viral proteins were established for the immunological detection of H5N1 influenza virus for research and diagnostic purposes. B-cell hybridomas were generated from mice that had been hyperimmunized with purified A/Vietnam/1194/2004 (NIBRG-14) virion that had been inactivated by UV-irradiation or formaldehyde. After screening over 4,000 hybridomas, eight H5N1-specific clones were selected. Six were specific for hemagglutinin (HA) and had in vitro neutralization activity. Of these, four were able to broadly detect all tested clades of the H5N1 strains. Five HA-specific mAbs detected denatured HA epitope(s) in Western blot analysis, and two detected HP influenza virus by immunofluorescence and immunohistochemistry. A highly sensitive antigen-capture sandwich ELISA system was established by combining mAbs with different specificities. In conclusion, these mAbs may be useful for rapid and specific diagnosis of H5N1 influenza. Therapeutically, they may have a role in antibody-based treatment of the disease

Benzyllithiums bearing aldehyde carbonyl groups. A flash chemistry approach.

Accepted 21 May 2015Reductive lithiation of benzyl halides bearing aldehyde carbonyl groups followed by reaction with subsequently added electrophiles was successfully accomplished without affecting the carbonyl groups by taking advantage of short residence times in flow microreactors