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1. Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

Author

Hassan, Manal, Li, Donghui, Han, Younghun, Byun, Jinyoung, Hatia, Rikita, Long, Erping, Choi, Jiyeon, Kelley, Robin, Cleary, Sean, Lok, Anna, Bracci, Paige, Permuth, Jennifer, Bucur, Roxana, Yuan, Jian-Min, Singal, Amit, Jalal, Prasun, Ghobrial, R, Santella, Regina, Kono, Yuko, Shah, Dimpy, Nguyen, Mindie, Liu, Geoffrey, Parikh, Neehar, Kim, Richard, Wu, Hui-Chen, El-Serag, Hashem, Chang, Ping, Li, Yanan, Chun, Yun, Lee, Sunyoung, Gu, Jian, Hawk, Ernest, Sun, Ryan, Huff, Chad, Rashid, Asif, Amin, Hesham, Beretta, Laura, Wolff, Robert, Antwi, Samuel, Patt, Yehuda, Hwang, Lu-Yu, Klein, Alison, Zhang, Karen, Schmidt, Mikayla, White, Donna, Goss, John, Khaderi, Saira, Marrero, Jorge, Cigarroa, Francisco, Shah, Pankil, Kaseb, Ahmed, Roberts, Lewis, and Amos, Christopher

Subjects
Humans, Genome-Wide Association Study, Liver Neoplasms, Genetic Predisposition to Disease, Carcinoma, Hepatocellular, Male, Female, Middle Aged, North America, Case-Control Studies, Polymorphism, Single Nucleotide, Aged, Genetic Loci, White People
Abstract

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Published
2024

2. Context-aware single-cell multiomics approach identifies cell-type-specific lung cancer susceptibility genes

Author

Long, Erping, Yin, Jinhu, Shin, Ju Hye, Li, Yuyan, Li, Bolun, Kane, Alexander, Patel, Harsh, Sun, Xinti, Wang, Cong, Luong, Thong, Xia, Jun, Han, Younghun, Byun, Jinyoung, Zhang, Tongwu, Zhao, Wei, Landi, Maria Teresa, Rothman, Nathaniel, Lan, Qing, Chang, Yoon Soo, Yu, Fulong, Amos, Christopher I., Shi, Jianxin, Lee, Jin Gu, Kim, Eun Young, and Choi, Jiyeon

Published
2024
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3. Author Correction: Context-aware single-cell multiomics approach identifies cell-type-specific lung cancer susceptibility genes

Author

Long, Erping, Yin, Jinhu, Shin, Ju Hye, Li, Yuyan, Li, Bolun, Kane, Alexander, Patel, Harsh, Sun, Xinti, Wang, Cong, Luong, Thong, Xia, Jun, Han, Younghun, Byun, Jinyoung, Zhang, Tongwu, Zhao, Wei, Landi, Maria Teresa, Rothman, Nathaniel, Lan, Qing, Chang, Yoon Soo, Yu, Fulong, Amos, Christopher I., Shi, Jianxin, Lee, Jin Gu, Kim, Eun Young, and Choi, Jiyeon

Published
2024
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4. Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk

Author

Gorman, Bryan R., Ji, Sun-Gou, Francis, Michael, Sendamarai, Anoop K., Shi, Yunling, Devineni, Poornima, Saxena, Uma, Partan, Elizabeth, DeVito, Andrea K., Byun, Jinyoung, Han, Younghun, Xiao, Xiangjun, Sin, Don D., Timens, Wim, Moser, Jennifer, Muralidhar, Sumitra, Ramoni, Rachel, Hung, Rayjean J., McKay, James D., Bossé, Yohan, Sun, Ryan, Amos, Christopher I., and Pyarajan, Saiju

Published
2024
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5. Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.

Author

Byun, Jinyoung, Han, Younghun, Li, Yafang, Xia, Jun, Long, Erping, Choi, Jiyeon, Xiao, Xiangjun, Zhu, Meng, Zhou, Wen, Sun, Ryan, Bossé, Yohan, Song, Zhuoyi, Schwartz, Ann, Lusk, Christine, Rafnar, Thorunn, Stefansson, Kari, Zhang, Tongwu, Zhao, Wei, Pettit, Rowland W, Liu, Yanhong, Li, Xihao, Zhou, Hufeng, Walsh, Kyle M, Gorlov, Ivan, Gorlova, Olga, Zhu, Dakai, Rosenberg, Susan M, Pinney, Susan, Bailey-Wilson, Joan E, Mandal, Diptasri, de Andrade, Mariza, Gaba, Colette, Willey, James C, You, Ming, Anderson, Marshall, Wiencke, John K, Albanes, Demetrius, Lam, Stephan, Tardon, Adonina, Chen, Chu, Goodman, Gary, Bojeson, Stig, Brenner, Hermann, Landi, Maria Teresa, Chanock, Stephen J, Johansson, Mattias, Muley, Thomas, Risch, Angela, Wichmann, H-Erich, Bickeböller, Heike, Christiani, David C, Rennert, Gad, Arnold, Susanne, Field, John K, Shete, Sanjay, Le Marchand, Loic, Melander, Olle, Brunnstrom, Hans, Liu, Geoffrey, Andrew, Angeline S, Kiemeney, Lambertus A, Shen, Hongbing, Zienolddiny, Shanbeh, Grankvist, Kjell, Johansson, Mikael, Caporaso, Neil, Cox, Angela, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B, Aldrich, Melinda C, Patel, Alpa, Lan, Qing, Rothman, Nathaniel, Taylor, Fiona, Kachuri, Linda, Witte, John S, Sakoda, Lori C, Spitz, Margaret, Brennan, Paul, Lin, Xihong, McKay, James, Hung, Rayjean J, and Amos, Christopher I

Subjects
Humans, Lung Neoplasms, Genetic Predisposition to Disease, RNA-Binding Proteins, DNA-Binding Proteins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Human Genome, Cancer, Genetics, Lung, 2.1 Biological and endogenous factors, Aetiology, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.

Published
2022

7. Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis

Author

Han, Younghun, Byun, Jinyoung, Zhu, Catherine, Sun, Ryan, Roh, Julia Y., Cordell, Heather J., Lee, Hyun-Sung, Shaw, Vikram R., Kang, Sung Wook, Razjouyan, Javad, Cooley, Matthew A., Hassan, Manal M., Siminovitch, Katherine A., Folseraas, Trine, Ellinghaus, David, Bergquist, Annika, Rushbrook, Simon M., Franke, Andre, Karlsen, Tom H., Lazaridis, Konstantinos N., McGlynn, Katherine A., Roberts, Lewis R., and Amos, Christopher I.

Published
2023
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9. Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From the INTEGRAL-ILCCO Cohort Analysis

Author

Cheng, Chao, Hong, Wei, Li, Yafang, Xiao, Xiangjun, McKay, James, Han, Younghun, Byun, Jinyoung, Peng, Bo, Albanes, Demetrios, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E., Landi, Maria T., Johansson, Mattias, Risch, Angela, Bickeböller, Heike, Wichmann, H-Erich, Christiani, David C., Rennert, Gad, Arnold, Susanne, Goodman, Gary, Field, John K., Davies, Michael P.A., Shete, Sanjay S., Le Marchand, Loic, Liu, Geoffrey, Hung, Rayjean J., Andrew, Angeline S., Kiemeney, Lambertus A., Zhu, Meng, Shen, Hongbing, Zienolddiny, Shan, Grankvist, Kjell, Johansson, Mikael, Cox, Angela, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Brennan, Paul, Li, Yong, Gorlova, Olga, Gorlov, Ivan, and Amos, Christopher I.

Published
2023
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10. Publisher Correction: Shared heritability and functional enrichment across six solid cancers.

Author

Jiang, Xia, Finucane, Hilary K, Schumacher, Fredrick R, Schmit, Stephanie L, Tyrer, Jonathan P, Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B, Dennis, Joe, Conti, David V, Casey, Graham, Gaudet, Mia M, Huyghe, Jeroen R, Albanes, Demetrius, Aldrich, Melinda C, Andrew, Angeline S, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Antonenkova, Natalia N, Arnold, Susanne M, Aronson, Kristan J, Arun, Banu K, Bandera, Elisa V, Barkardottir, Rosa B, Barnes, Daniel R, Batra, Jyotsna, Beckmann, Matthias W, Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I, Bickeböller, Heike, Bien, Stephanie A, Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Brauch, Hiltrud, Brenner, Hermann, Brenton, James D, Brook, Mark N, Brunet, Joan, Brunnström, Hans, Buchanan, Daniel D, Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Campbell, Peter T, Cancel-Tassin, Géraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, André L, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Chu, Christiani, David C, Claes, Kathleen BM, Claessens, Frank, Clements, Judith, Collée, J Margriet, Correa, Marcia Cruz, Couch, Fergus J, Cox, Angela, Cunningham, Julie M, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, deFazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L, Dörk, Thilo, Duell, Eric J, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Edlund, Christopher K, Edwards, Digna R Velez, Ellberg, Carolina, Evans, D Gareth, Fasching, Peter A, Ferris, Robert L, Liloglou, Triantafillos, Figueiredo, Jane C, Fletcher, Olivia, Fortner, Renée T, Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J, and Ganz, Patricia A

Subjects
MD Multidisciplinary
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

11. Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region

Author

Hung, Rayjean J, Spitz, Margaret R, Houlston, Richard S, Schwartz, Ann G, Field, John K, Ying, Jun, Li, Yafang, Han, Younghun, Ji, Xuemei, Chen, Wei, Wu, Xifeng, Gorlov, Ivan P, Na, Jie, de Andrade, Mariza, Liu, Geoffrey, Brhane, Yonathan, Diao, Nancy, Wenzlaff, Angela, Davies, Michael PA, Liloglou, Triantafillos, Timofeeva, Maria, Muley, Thomas, Rennert, Hedy, Saliba, Walid, Ryan, Bríd M, Bowman, Elise, Barros-Dios, Juan-Miguel, Pérez-Ríos, Mónica, Morgenstern, Hal, Zienolddiny, Shanbeh, Skaug, Vidar, Ugolini, Donatella, Bonassi, Stefano, van der Heijden, Erik HFM, Tardon, Adonina, Bojesen, Stig E, Landi, Maria Teresa, Johansson, Mattias, Bickeböller, Heike, Arnold, Susanne, Le Marchand, Loic, Melander, Olle, Andrew, Angeline, Grankvist, Kjell, Caporaso, Neil, Teare, M Dawn, Schabath, Matthew B, Aldrich, Melinda C, Kiemeney, Lambertus A, Wichmann, H-Erich, Lazarus, Philip, Mayordomo, Jose, Neri, Monica, Haugen, Aage, Zhang, Zuo-Feng, Ruano-Raviña, Alberto, Brenner, Hermann, Harris, Curtis C, Orlow, Irene, Rennert, Gadi, Risch, Angela, Brennan, Paul, Christiani, David C, Amos, Christopher I, Yang, Ping, and Gorlova, Olga Y

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Lung Cancer, Tobacco, Prevention, Cancer, Genetics, Clinical Research, Tobacco Smoke and Health, Lung, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Case-Control Studies, Chromosomes, Human, Pair 5, Europe, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotyping Techniques, Humans, Lung Neoplasms, Membrane Proteins, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Telomerase, Lung cancer, Never smokers, Genome-wide association study, Genetic susceptibility, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

IntroductionInherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer.MethodsWe conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer.ResultsWe detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 × 10-16), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 × 10-16), and rs4975616 (OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 × 10-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate.ConclusionsWe found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.

Published
2019

12. Shared heritability and functional enrichment across six solid cancers.

Author

Jiang, Xia, Finucane, Hilary K, Schumacher, Fredrick R, Schmit, Stephanie L, Tyrer, Jonathan P, Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B, Dennis, Joe, Conti, David V, Casey, Graham, Gaudet, Mia M, Huyghe, Jeroen R, Albanes, Demetrius, Aldrich, Melinda C, Andrew, Angeline S, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Antonenkova, Natalia N, Arnold, Susanne M, Aronson, Kristan J, Arun, Banu K, Bandera, Elisa V, Barkardottir, Rosa B, Barnes, Daniel R, Batra, Jyotsna, Beckmann, Matthias W, Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I, Bickeböller, Heike, Bien, Stephanie A, Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Brauch, Hiltrud, Brenner, Hermann, Brenton, James D, Brook, Mark N, Brunet, Joan, Brunnström, Hans, Buchanan, Daniel D, Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Campbell, Peter T, Cancel-Tassin, Géraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, André L, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Chu, Christiani, David C, Claes, Kathleen BM, Claessens, Frank, Clements, Judith, Collée, J Margriet, Correa, Marcia Cruz, Couch, Fergus J, Cox, Angela, Cunningham, Julie M, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, deFazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L, Dörk, Thilo, Duell, Eric J, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Edlund, Christopher K, Edwards, Digna R Velez, Ellberg, Carolina, Evans, D Gareth, Fasching, Peter A, Ferris, Robert L, Liloglou, Triantafillos, Figueiredo, Jane C, Fletcher, Olivia, Fortner, Renée T, Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J, and Ganz, Patricia A

Subjects
Humans, Breast Neoplasms, Colorectal Neoplasms, Ovarian Neoplasms, Head and Neck Neoplasms, Lung Neoplasms, Prostatic Neoplasms, Genetic Predisposition to Disease, Neoplasm Proteins, Case-Control Studies, Smoking, Mental Disorders, Inheritance Patterns, Phenotype, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Prevention, Cancer, Breast Cancer, Genetics, Rare Diseases, Lung Cancer, Human Genome, Colo-Rectal Cancer, Digestive Diseases, Lung, MD Multidisciplinary
Abstract

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

Published
2019

13. Deciphering associations between three RNA splicing-related genetic variants and lung cancer risk

Author

Yang, Wenjun, Liu, Hongliang, Zhang, Ruoxin, Freedman, Jennifer A., Han, Younghun, Hung, Rayjean J., Brhane, Yonathan, McLaughlin, John, Brennan, Paul, Bickeboeller, Heike, Rosenberger, Albert, Houlston, Richard S., Caporaso, Neil E., Landi, Maria Teresa, Brueske, Irene, Risch, Angela, Christiani, David C., Amos, Christopher I., Chen, Xiaoxin, Patierno, Steven R., and Wei, Qingyi

Published
2022
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15. Genomic Insights for Personalized Care: Motivating At-Risk Individuals Toward Evidence-Based Health Practices

Author

Chen, Tony, primary, Pham, Giang, additional, Fox, Louis, additional, Zhang, Jingning, additional, Byun, Jinyoung, additional, Han, Younghun, additional, Saunders, Gretchen RB, additional, Liu, Dajiang, additional, Bray, Michael J, additional, Ramsey, Alex T, additional, McKay, James, additional, Bierut, Laura J, additional, Amos, Christopher Ian, additional, Hung, Rayjean J., additional, Lin, Xihong, additional, Zhang, Haoyu, additional, and Chen, Li-Shiun, additional

Published
2024
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16. Supplementary Table S6 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Author

Li, Yafang, primary, Xiao, Xiangjun, primary, Li, Jianrong, primary, Han, Younghun, primary, Cheng, Chao, primary, Fernandes, Gail F., primary, Slewitzke, Shannon E., primary, Rosenberg, Susan M., primary, Zhu, Meng, primary, Byun, Jinyoung, primary, Bossé, Yohan, primary, McKay, James D., primary, Albanes, Demetrios, primary, Lam, Stephen, primary, Tardon, Adonina, primary, Chen, Chu, primary, Bojesen, Stig E., primary, Landi, Maria T., primary, Johansson, Mattias, primary, Risch, Angela, primary, Bickeböller, Heike, primary, Wichmann, H-Erich, primary, Christiani, David C., primary, Rennert, Gad, primary, Arnold, Susanne M., primary, Goodman, Gary E., primary, Field, John K., primary, Davies, Michael P.A., primary, Shete, Sanjay, primary, Marchand, Loïc Le, primary, Liu, Geoffrey, primary, Hung, Rayjean J., primary, Andrew, Angeline S., primary, Kiemeney, Lambertus A., primary, Sun, Ryan, primary, Zienolddiny, Shanbeh, primary, Grankvist, Kjell, primary, Johansson, Mikael, primary, Caporaso, Neil E., primary, Cox, Angela, primary, Hong, Yun-Chul, primary, Lazarus, Philip, primary, Schabath, Matthew B., primary, Aldrich, Melinda C., primary, Schwartz, Ann G., primary, Gorlov, Ivan, primary, Purrington, Kristen S., primary, Yang, Ping, primary, Liu, Yanhong, primary, Bailey-Wilson, Joan E., primary, Pinney, Susan M., primary, Mandal, Diptasri, primary, Willey, James C., primary, Gaba, Colette, primary, Brennan, Paul, primary, Xia, Jun, primary, Shen, Hongbing, primary, and Amos, Christopher I., primary

Published
2024
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17. Data from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Author

Li, Yafang, primary, Xiao, Xiangjun, primary, Li, Jianrong, primary, Han, Younghun, primary, Cheng, Chao, primary, Fernandes, Gail F., primary, Slewitzke, Shannon E., primary, Rosenberg, Susan M., primary, Zhu, Meng, primary, Byun, Jinyoung, primary, Bossé, Yohan, primary, McKay, James D., primary, Albanes, Demetrios, primary, Lam, Stephen, primary, Tardon, Adonina, primary, Chen, Chu, primary, Bojesen, Stig E., primary, Landi, Maria T., primary, Johansson, Mattias, primary, Risch, Angela, primary, Bickeböller, Heike, primary, Wichmann, H-Erich, primary, Christiani, David C., primary, Rennert, Gad, primary, Arnold, Susanne M., primary, Goodman, Gary E., primary, Field, John K., primary, Davies, Michael P.A., primary, Shete, Sanjay, primary, Marchand, Loïc Le, primary, Liu, Geoffrey, primary, Hung, Rayjean J., primary, Andrew, Angeline S., primary, Kiemeney, Lambertus A., primary, Sun, Ryan, primary, Zienolddiny, Shanbeh, primary, Grankvist, Kjell, primary, Johansson, Mikael, primary, Caporaso, Neil E., primary, Cox, Angela, primary, Hong, Yun-Chul, primary, Lazarus, Philip, primary, Schabath, Matthew B., primary, Aldrich, Melinda C., primary, Schwartz, Ann G., primary, Gorlov, Ivan, primary, Purrington, Kristen S., primary, Yang, Ping, primary, Liu, Yanhong, primary, Bailey-Wilson, Joan E., primary, Pinney, Susan M., primary, Mandal, Diptasri, primary, Willey, James C., primary, Gaba, Colette, primary, Brennan, Paul, primary, Xia, Jun, primary, Shen, Hongbing, primary, and Amos, Christopher I., primary

Published
2024
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18. Figure S4 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Author

Li, Yafang, primary, Xiao, Xiangjun, primary, Li, Jianrong, primary, Han, Younghun, primary, Cheng, Chao, primary, Fernandes, Gail F., primary, Slewitzke, Shannon E., primary, Rosenberg, Susan M., primary, Zhu, Meng, primary, Byun, Jinyoung, primary, Bossé, Yohan, primary, McKay, James D., primary, Albanes, Demetrios, primary, Lam, Stephen, primary, Tardon, Adonina, primary, Chen, Chu, primary, Bojesen, Stig E., primary, Landi, Maria T., primary, Johansson, Mattias, primary, Risch, Angela, primary, Bickeböller, Heike, primary, Wichmann, H-Erich, primary, Christiani, David C., primary, Rennert, Gad, primary, Arnold, Susanne M., primary, Goodman, Gary E., primary, Field, John K., primary, Davies, Michael P.A., primary, Shete, Sanjay, primary, Marchand, Loïc Le, primary, Liu, Geoffrey, primary, Hung, Rayjean J., primary, Andrew, Angeline S., primary, Kiemeney, Lambertus A., primary, Sun, Ryan, primary, Zienolddiny, Shanbeh, primary, Grankvist, Kjell, primary, Johansson, Mikael, primary, Caporaso, Neil E., primary, Cox, Angela, primary, Hong, Yun-Chul, primary, Lazarus, Philip, primary, Schabath, Matthew B., primary, Aldrich, Melinda C., primary, Schwartz, Ann G., primary, Gorlov, Ivan, primary, Purrington, Kristen S., primary, Yang, Ping, primary, Liu, Yanhong, primary, Bailey-Wilson, Joan E., primary, Pinney, Susan M., primary, Mandal, Diptasri, primary, Willey, James C., primary, Gaba, Colette, primary, Brennan, Paul, primary, Xia, Jun, primary, Shen, Hongbing, primary, and Amos, Christopher I., primary

Published
2024
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19. FastPop: a rapid principal component derived method to infer intercontinental ancestry using genetic data

Author

Li, Yafang, Byun, Jinyoung, Cai, Guoshuai, Xiao, Xiangjun, Han, Younghun, Cornelis, Olivier, Dinulos, James E, Dennis, Joe, Easton, Douglas, Gorlov, Ivan, Seldin, Michael F, and Amos, Christopher I

Subjects
Mathematical Sciences, Biological Sciences, Statistics, Genetics, Algorithms, Bayes Theorem, Ethnicity, Genetics, Population, Genome-Wide Association Study, Genotype, HapMap Project, Humans, Polymorphism, Single Nucleotide, Principal Component Analysis, Racial Groups, Software, Population structure, Principal component, Ancestry, Genome-wide association study, Information and Computing Sciences, Bioinformatics, Biological sciences, Information and computing sciences, Mathematical sciences
Abstract

BackgroundIdentifying subpopulations within a study and inferring intercontinental ancestry of the samples are important steps in genome wide association studies. Two software packages are widely used in analysis of substructure: Structure and Eigenstrat. Structure assigns each individual to a population by using a Bayesian method with multiple tuning parameters. It requires considerable computational time when dealing with thousands of samples and lacks the ability to create scores that could be used as covariates. Eigenstrat uses a principal component analysis method to model all sources of sampling variation. However, it does not readily provide information directly relevant to ancestral origin; the eigenvectors generated by Eigenstrat are sample specific and thus cannot be generalized to other individuals.ResultsWe developed FastPop, an efficient R package that fills the gap between Structure and Eigenstrat. It can: 1, generate PCA scores that identify ancestral origins and can be used for multiple studies; 2, infer ancestry information for data arising from two or more intercontinental origins. We demonstrate the use of FastPop using 2318 SNP markers selected from the genome based on high variability among European, Asian and West African (African) populations. We conducted an analysis of 505 Hapmap samples with European, African or Asian ancestry along with 19661 additional samples of unknown ancestry. The results from FastPop are highly consistent with those obtained by Structure across the 19661 samples we studied. The correlations of the results between FastPop and Structure are 0.99, 0.97 and 0.99 for European, African and Asian ancestry scores, respectively. Compared with Structure, FastPop is more efficient as it finished ancestry inference for 19661 samples in 16 min compared with 21-24 h required by Structure. FastPop also provided scores based on SNP weights so the scores of reference population can be applied to other studies provided the same set of markers are used. We also present application of the method for studying four continental populations (European, Asian, African, and Native American).ConclusionsWe developed an algorithm that can infer ancestries on data involving two or more intercontinental origins. It is efficient for analyzing large datasets. Additionally the PCA derived scores can be applied to multiple data sets to ensure the same ancestry analysis is applied to all studies.

Published
2016

20. Pleiotropic Analysis of Lung Cancer and Blood Triglycerides

Author

Zuber, Verena, Marconett, Crystal N, Shi, Jianxin, Hua, Xing, Wheeler, William, Yang, Chenchen, Song, Lei, Dale, Anders M, Laplana, Marina, Risch, Angela, Witoelar, Aree, Thompson, Wesley K, Schork, Andrew J, Bettella, Francesco, Wang, Yunpeng, Djurovic, Srdjan, Zhou, Beiyun, Borok, Zea, van der Heijden, Henricus FM, de Graaf, Jacqueline, Swinkels, Dorine, Aben, Katja K, McKay, James, Hung, Rayjean J, Bikeböller, Heike, Stevens, Victoria L, Albanes, Demetrius, Caporaso, Neil E, Han, Younghun, Wei, Yongyue, Panadero, Maria Angeles, Mayordomo, Jose I, Christiani, David C, Kiemeney, Lambertus, Andreassen, Ole A, Houlston, Richard, Amos, Christopher I, Chatterjee, Nilanjan, Laird-Offringa, Ite A, Mills, Ian G, and Landi, Maria Teresa

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Lung, Tobacco Smoke and Health, Genetics, Human Genome, Tobacco, Prevention, Lung Cancer, Cancer, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular Diseases, Case-Control Studies, Chromosomes, Human, Pair 6, Genetic Pleiotropy, Genome-Wide Association Study, Humans, Lung Neoplasms, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Risk Factors, Triglycerides, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10(-6)) and blood triglycerides (P = 1.39x10(-5)). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10(-4)) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21 ,: Pcombined = 5.20x10(-9)). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer.

Published
2016

21. Lung cancer in ever- and never-smokers : findings from multi-population GWAS studies

Author

Li, Yafang, Xiao, Xiangjun, Li, Jianrong, Han, Younghun, Cheng, Chao, Fernandes, Gail F., Slewitzke, Shannon E., Rosenberg, Susan M., Zhu, Meng, Byun, Jinyoung, Bossé, Yohan, McKay, James D., Albanes, Demetrios, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E., Landi, Maria T., Johansson, Mattias, Risch, Angela, Bickeböller, Heike, Wichmann, H-Erich, Christiani, David C., Rennert, Gad, Arnold, Susanne M., Goodman, Gary E., Field, John K., Davies, Michael P A, Shete, Sanjay, Marchand, Loïc Le, Liu, Geoffrey, Hung, Rayjean J., Andrew, Angeline S., Kiemeney, Lambertus A., Sun, Ryan, Zienolddiny, Shanbeh, Grankvist, Kjell, Johansson, Mikael, Caporaso, Neil E., Cox, Angela, Hong, Yun-Chul, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Schwartz, Ann G., Gorlov, Ivan, Purrington, Kristen S., Yang, Ping, Liu, Yanhong, Bailey-Wilson, Joan E., Pinney, Susan M., Mandal, Diptasri, Willey, James C., Gaba, Colette, Brennan, Paul, Xia, Jun, Shen, Hongbing, Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Li, Jianrong, Han, Younghun, Cheng, Chao, Fernandes, Gail F., Slewitzke, Shannon E., Rosenberg, Susan M., Zhu, Meng, Byun, Jinyoung, Bossé, Yohan, McKay, James D., Albanes, Demetrios, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E., Landi, Maria T., Johansson, Mattias, Risch, Angela, Bickeböller, Heike, Wichmann, H-Erich, Christiani, David C., Rennert, Gad, Arnold, Susanne M., Goodman, Gary E., Field, John K., Davies, Michael P A, Shete, Sanjay, Marchand, Loïc Le, Liu, Geoffrey, Hung, Rayjean J., Andrew, Angeline S., Kiemeney, Lambertus A., Sun, Ryan, Zienolddiny, Shanbeh, Grankvist, Kjell, Johansson, Mikael, Caporaso, Neil E., Cox, Angela, Hong, Yun-Chul, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Schwartz, Ann G., Gorlov, Ivan, Purrington, Kristen S., Yang, Ping, Liu, Yanhong, Bailey-Wilson, Joan E., Pinney, Susan M., Mandal, Diptasri, Willey, James C., Gaba, Colette, Brennan, Paul, Xia, Jun, Shen, Hongbing, and Amos, Christopher I.

Abstract

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.

Published
2024
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25. Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies

Author

Li, Yafang, primary, Xiao, Xiangjun, additional, Li, Jianrong, additional, Han, Younghun, additional, Cheng, Chao, additional, Fernandes, Gail F., additional, Slewitzke, Shannon E., additional, Rosenberg, Susan M., additional, Zhu, Meng, additional, Byun, Jinyoung, additional, Bossé, Yohan, additional, McKay, James D., additional, Albanes, Demetrios, additional, Lam, Stephen, additional, Tardon, Adonina, additional, Chen, Chu, additional, Bojesen, Stig E., additional, Landi, Maria T., additional, Johansson, Mattias, additional, Risch, Angela, additional, Bickeböller, Heike, additional, Wichmann, H-Erich, additional, Christiani, David C., additional, Rennert, Gad, additional, Arnold, Susanne M., additional, Goodman, Gary E., additional, Field, John K., additional, Davies, Michael P.A., additional, Shete, Sanjay, additional, Marchand, Loïc Le, additional, Liu, Geoffrey, additional, Hung, Rayjean J., additional, Andrew, Angeline S., additional, Kiemeney, Lambertus A., additional, Sun, Ryan, additional, Zienolddiny, Shanbeh, additional, Grankvist, Kjell, additional, Johansson, Mikael, additional, Caporaso, Neil E., additional, Cox, Angela, additional, Hong, Yun-Chul, additional, Lazarus, Philip, additional, Schabath, Matthew B., additional, Aldrich, Melinda C., additional, Schwartz, Ann G., additional, Gorlov, Ivan, additional, Purrington, Kristen S., additional, Yang, Ping, additional, Liu, Yanhong, additional, Bailey-Wilson, Joan E., additional, Pinney, Susan M., additional, Mandal, Diptasri, additional, Willey, James C., additional, Gaba, Colette, additional, Brennan, Paul, additional, Xia, Jun, additional, Shen, Hongbing, additional, and Amos, Christopher I., additional

Published
2024
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27. CHRNA5 Risk Variant Predicts Delayed Smoking Cessation and Earlier Lung Cancer Diagnosis—A Meta-Analysis

Author

Chen, Li-Shiun, Hung, Rayjean J, Baker, Timothy, Horton, Amy, Culverhouse, Rob, Saccone, Nancy, Cheng, Iona, Deng, Bo, Han, Younghun, Hansen, Helen M, Horsman, Janet, Kim, Claire, Lutz, Sharon, Rosenberger, Albert, Aben, Katja K, Andrew, Angeline S, Breslau, Naomi, Chang, Shen-Chih, Dieffenbach, Aida Karina, Dienemann, Hendrik, Frederiksen, Brittni, Han, Jiali, Hatsukami, Dorothy K, Johnson, Eric O, Pande, Mala, Wrensch, Margaret R, McLaughlin, John, Skaug, Vidar, van der Heijden, Henricus F, Wampfler, Jason, Wenzlaff, Angela, Woll, Penella, Zienolddiny, Shanbeh, Bickeböller, Heike, Brenner, Hermann, Duell, Eric J, Haugen, Aage, Heinrich, Joachim, Hokanson, John E, Hunter, David J, Kiemeney, Lambertus A, Lazarus, Philip, Le Marchand, Loic, Liu, Geoffrey, Mayordomo, Jose, Risch, Angela, Schwartz, Ann G, Teare, Dawn, Wu, Xifeng, Wiencke, John K, Yang, Ping, Zhang, Zuo-Feng, Spitz, Margaret R, Kraft, Peter, Amos, Christopher I, and Bierut, Laura J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Lung, Lung Cancer, Cancer, Human Genome, Tobacco, Prevention, Genetics, Tobacco Smoke and Health, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Respiratory, Good Health and Well Being, Genetic Variation, Humans, Lung Neoplasms, Middle Aged, Nerve Tissue Proteins, Phenotype, Receptors, Nicotinic, Risk Factors, Smoking, Smoking Cessation, Time Factors, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundRecent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis.MethodsMeta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each dataset, we used Cox regression models to evaluate the association between rs16969968 and the two primary phenotypes (age of smoking cessation among ever smokers and age of lung cancer diagnosis among lung cancer case patients) and the secondary phenotype of smoking duration. Heterogeneity across studies was assessed with the Cochran Q test. All statistical tests were two-sided.ResultsThe rs16969968 allele (A) was associated with a lower likelihood of smoking cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98, P = .0042), and the AA genotype was associated with a four-year delay in median age of quitting compared with the GG genotype. Among smokers with lung cancer diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95% CI = 1.04 to 1.12, P = 1.1*10(-5)).ConclusionThese data support the clinical significance of the CHRNA5 variant rs16969968. It predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis. Given the existing evidence that this CHRNA5 variant predicts favorable response to cessation pharmacotherapy, these findings underscore the potential clinical and public health importance of rs16969968 in CHRNA5 in relation to smoking cessation success and lung cancer risk.

Published
2015

32. Context-aware single-cell multiome approach identified cell-type specific lung cancer susceptibility genes

Author

Long, Erping, primary, Yin, Jinhu, additional, Shin, Ju Hye, additional, Li, Yuyan, additional, Kane, Alexander, additional, Patel, Harsh, additional, Luong, Thong, additional, Xia, Jun, additional, Han, Younghun, additional, Byun, Jinyoung, additional, Zhang, Tongwu, additional, Zhao, Wei, additional, Landi, Maria Teresa, additional, Rothman, Nathaniel, additional, Lan, Qing, additional, Chang, Yoon Soo, additional, Yu, Fulong, additional, Amos, Christopher, additional, Shi, Jianxin, additional, Lee, Jin Gu, additional, Kim, Eun Young, additional, and Choi, Jiyeon, additional

Published
2023
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33. Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma

Author

Hatia, Rikita I., primary, Eluri, Madhulika, additional, Hawk, Ernest T., additional, Shalaby, Akram, additional, Karatas, Elif, additional, Shalaby, Ahmed, additional, Abdelhakeem, Ahmed, additional, Abdel-Wahab, Reham, additional, Chang, Ping, additional, Rashid, Asif, additional, Jalal, Prasun K., additional, Amos, Christopher I., additional, Han, Younghun, additional, Armaghany, Tannaz, additional, Shroff, Rachna T., additional, Li, Donghui, additional, Javle, Milind, additional, and Hassan, Manal M., additional

Published
2023
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35. A Feature-Oriented Mobile Software Development Framework to Resolve the Device Fragmentation Phenomenon for Application Developers in the Mobile Software Ecosystem

Author

Han, Younghun, Go, Gyeongmin, Kang, Sungwon, Lee, Heuijin, Akan, Ozgur, Series editor, Bellavista, Paolo, Series editor, Cao, Jiannong, Series editor, Coulson, Geoffrey, Series editor, Dressler, Falko, Series editor, Ferrari, Domenico, Series editor, Gerla, Mario, Series editor, Kobayashi, Hisashi, Series editor, Palazzo, Sergio, Series editor, Sahni, Sartaj, Series editor, Shen, Xuemin (Sherman), Series editor, Stan, Mircea, Series editor, Xiaohua, Jia, Series editor, Zomaya, Albert Y., Series editor, Zhang, Yin, editor, Peng, Limei, editor, and Youn, Chan-Hyun, editor

Published
2016
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36. Protein-altering germline mutations implicate novel genes related to lung cancer development

Author

Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus FA., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Heijden, Erik H. F. M. van der, Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma’en, Timens, Wim, Artigas, María Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., and Amos, Christopher I.

Published
2020
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37. Corrigendum to: “An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs” [J Hepatol 75 (2021) 572-581]

Author

Cordell, Heather J., primary, Fryett, James J., additional, Ueno, Kazuko, additional, Darlay, Rebecca, additional, Aiba, Yoshihiro, additional, Hitomi, Yuki, additional, Kawashima, Minae, additional, Nishida, Nao, additional, Khor, Seik-Soon, additional, Gervais, Olivier, additional, Kawai, Yosuke, additional, Nagasaki, Masao, additional, Tokunaga, Katsushi, additional, Tang, Ruqi, additional, Shi, Yongyong, additional, Li, Zhiqiang, additional, Juran, Brian D., additional, Atkinson, Elizabeth J., additional, Gerussi, Alessio, additional, Carbone, Marco, additional, Asselta, Rosanna, additional, Cheung, Angela, additional, de Andrade, Mariza, additional, Baras, Aris, additional, Horowitz, Julie, additional, Ferreira, Manuel A.R., additional, Sun, Dylan, additional, Jones, David E., additional, Flack, Steven, additional, Spicer, Ann, additional, Mulcahy, Victoria L., additional, Byan, Jinyoung, additional, Han, Younghun, additional, Sandford, Richard N., additional, Lazaridis, Konstantinos N., additional, Amos, Christopher I., additional, Hirschfield, Gideon M., additional, Seldin, Michael F., additional, Invernizzi, Pietro, additional, Siminovitch, Katherine A., additional, Ma, Xiong, additional, Nakamura, Minoru, additional, and Mells, George F., additional

Published
2023
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39. Table S3. Top pathways and pathway-smoking interactions that are associated with lung adenocarcinoma. from A Novel Pathway-Based Approach Improves Lung Cancer Risk Prediction Using Germline Genetic Variations

Author

Qian, David C., primary, Han, Younghun, primary, Byun, Jinyoung, primary, Shin, Hae Ri, primary, Hung, Rayjean J., primary, McLaughlin, John R., primary, Landi, Maria Teresa, primary, Seminara, Daniela, primary, and Amos, Christopher I., primary

Published
2023
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40. Table S2. Top pathways and pathway-smoking interactions that are associated with overall lung cancer. from A Novel Pathway-Based Approach Improves Lung Cancer Risk Prediction Using Germline Genetic Variations

Author

Qian, David C., primary, Han, Younghun, primary, Byun, Jinyoung, primary, Shin, Hae Ri, primary, Hung, Rayjean J., primary, McLaughlin, John R., primary, Landi, Maria Teresa, primary, Seminara, Daniela, primary, and Amos, Christopher I., primary

Published
2023
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41. Data from Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk

Author

Patel, Yesha M., primary, Park, Sunghim L., primary, Han, Younghun, primary, Wilkens, Lynne R., primary, Bickeböller, Heike, primary, Rosenberger, Albert, primary, Caporaso, Neil, primary, Landi, Maria Teresa, primary, Brüske, Irene, primary, Risch, Angela, primary, Wei, Yongyue, primary, Christiani, David C., primary, Brennan, Paul, primary, Houlston, Richard, primary, McKay, James, primary, McLaughlin, John, primary, Hung, Rayjean, primary, Murphy, Sharon, primary, Stram, Daniel O., primary, Amos, Christopher, primary, and Le Marchand, Loïc, primary

Published
2023
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42. Supplemental Table 5 from Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk

Author

Patel, Yesha M., primary, Park, Sunghim L., primary, Han, Younghun, primary, Wilkens, Lynne R., primary, Bickeböller, Heike, primary, Rosenberger, Albert, primary, Caporaso, Neil, primary, Landi, Maria Teresa, primary, Brüske, Irene, primary, Risch, Angela, primary, Wei, Yongyue, primary, Christiani, David C., primary, Brennan, Paul, primary, Houlston, Richard, primary, McKay, James, primary, McLaughlin, John, primary, Hung, Rayjean, primary, Murphy, Sharon, primary, Stram, Daniel O., primary, Amos, Christopher, primary, and Le Marchand, Loïc, primary

Published
2023
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43. Table S4. Top pathways and pathway-smoking interactions that are associated with lung squamous cell carcinoma. from A Novel Pathway-Based Approach Improves Lung Cancer Risk Prediction Using Germline Genetic Variations

Author

Qian, David C., primary, Han, Younghun, primary, Byun, Jinyoung, primary, Shin, Hae Ri, primary, Hung, Rayjean J., primary, McLaughlin, John R., primary, Landi, Maria Teresa, primary, Seminara, Daniela, primary, and Amos, Christopher I., primary

Published
2023
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44. Supplemental Table 3 from Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk

Author

Patel, Yesha M., primary, Park, Sunghim L., primary, Han, Younghun, primary, Wilkens, Lynne R., primary, Bickeböller, Heike, primary, Rosenberger, Albert, primary, Caporaso, Neil, primary, Landi, Maria Teresa, primary, Brüske, Irene, primary, Risch, Angela, primary, Wei, Yongyue, primary, Christiani, David C., primary, Brennan, Paul, primary, Houlston, Richard, primary, McKay, James, primary, McLaughlin, John, primary, Hung, Rayjean, primary, Murphy, Sharon, primary, Stram, Daniel O., primary, Amos, Christopher, primary, and Le Marchand, Loïc, primary

Published
2023
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45. Data from Genetic Determinants for Promoter Hypermethylation in the Lungs of Smokers: A Candidate Gene-Based Study

Author

Leng, Shuguang, primary, Stidley, Christine A., primary, Liu, Yushi, primary, Edlund, Christopher K., primary, Willink, Randall P., primary, Han, Younghun, primary, Landi, Maria Teresa, primary, Thun, Michael, primary, Picchi, Maria A., primary, Bruse, Shannon E., primary, Crowell, Richard E., primary, Van Den Berg, David, primary, Caporaso, Neil E., primary, Amos, Christopher I., primary, Siegfried, Jill M., primary, Tesfaigzi, Yohannes, primary, Gilliland, Frank D., primary, and Belinsky, Steven A., primary

Published
2023
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46. Supplementary Tables 1-3, Figure 1 from Genetic Determinants for Promoter Hypermethylation in the Lungs of Smokers: A Candidate Gene-Based Study

Author

Leng, Shuguang, primary, Stidley, Christine A., primary, Liu, Yushi, primary, Edlund, Christopher K., primary, Willink, Randall P., primary, Han, Younghun, primary, Landi, Maria Teresa, primary, Thun, Michael, primary, Picchi, Maria A., primary, Bruse, Shannon E., primary, Crowell, Richard E., primary, Van Den Berg, David, primary, Caporaso, Neil E., primary, Amos, Christopher I., primary, Siegfried, Jill M., primary, Tesfaigzi, Yohannes, primary, Gilliland, Frank D., primary, and Belinsky, Steven A., primary

Published
2023
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47. Supplementary Methods from Genetic Determinants for Promoter Hypermethylation in the Lungs of Smokers: A Candidate Gene-Based Study

Author

Leng, Shuguang, primary, Stidley, Christine A., primary, Liu, Yushi, primary, Edlund, Christopher K., primary, Willink, Randall P., primary, Han, Younghun, primary, Landi, Maria Teresa, primary, Thun, Michael, primary, Picchi, Maria A., primary, Bruse, Shannon E., primary, Crowell, Richard E., primary, Van Den Berg, David, primary, Caporaso, Neil E., primary, Amos, Christopher I., primary, Siegfried, Jill M., primary, Tesfaigzi, Yohannes, primary, Gilliland, Frank D., primary, and Belinsky, Steven A., primary

Published
2023
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49. Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk:Insight From the INTEGRAL-ILCCO Cohort Analysis

Author

Cheng, Chao, Hong, Wei, Li, Yafang, Xiao, Xiangjun, McKay, James, Han, Younghun, Byun, Jinyoung, Peng, Bo, Albanes, Demetrios, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E., Landi, Maria T., Johansson, Mattias, Risch, Angela, Bickeböller, Heike, Wichmann, H.-Erich, Christiani, David C., Rennert, Gad, Arnold, Susanne, Goodman, Gary, Field, John K., Davies, Michael P. A., Shete, Sanjay S., Le Marchand, Loic, Liu, Geoffrey, Hung, Rayjean J., Andrew, Angeline S., Kiemeney, Lambertus A., Zhu, Meng, Shen, Hongbing, Zienolddiny, Shan, Grankvist, Kjell, Johansson, Mikael, Cox, Angela, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Brennan, Paul, Li, Yong, Gorlova, Olga, Gorlov, Ivan, Amos, Christopher I., Cheng, Chao, Hong, Wei, Li, Yafang, Xiao, Xiangjun, McKay, James, Han, Younghun, Byun, Jinyoung, Peng, Bo, Albanes, Demetrios, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E., Landi, Maria T., Johansson, Mattias, Risch, Angela, Bickeböller, Heike, Wichmann, H.-Erich, Christiani, David C., Rennert, Gad, Arnold, Susanne, Goodman, Gary, Field, John K., Davies, Michael P. A., Shete, Sanjay S., Le Marchand, Loic, Liu, Geoffrey, Hung, Rayjean J., Andrew, Angeline S., Kiemeney, Lambertus A., Zhu, Meng, Shen, Hongbing, Zienolddiny, Shan, Grankvist, Kjell, Johansson, Mikael, Cox, Angela, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Brennan, Paul, Li, Yong, Gorlova, Olga, Gorlov, Ivan, and Amos, Christopher I.

Abstract

Introduction: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer. Methods: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls. Results: We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal mCAs were detected in 4.3% of subjects, in addition to ChrX mCAs in 3.6% of females and mChrY losses in 9.6% of males. Multivariable logistic regression analysis indicated that the presence of autosomal mCAs in white blood cells was associated with an increased lung cancer risk after adjusting for key confounding factors, including age, sex, smoking status, and race. This association was mainly driven by a specific type of mCAs: copy-neutral loss of heterozygosity on autosomal chromosomes. The association between autosome copy-neutral loss of heterozygosity and increased risk of lung cancer was further confirmed in two major histologic subtypes, lung adenocarcinoma and squamous cell carcinoma. In addition, we observed a significant increase of ChrX mCAs and mChrY losses in smokers compared with nonsmokers and racial differences in certain types of mCA events. Conclusions: Our study established a link between mCAs in white blood cells and increased risk of lung cancer.

Published
2023

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