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2. Determinants and prognostic value of quality of life in patients with pancreatic ductal adenocarcinoma

Author

Deng, Yang, Tu, Huakang, Pierzynski, Jeanne A, Miller, Ethan D, Gu, Xiangjun, Huang, Maosheng, Chang, David W, Ye, Yuanqing, Hildebrandt, Michelle AT, Klein, Alison P, Zhao, Ren, Lippman, Scott M, and Wu, Xifeng

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Digestive Diseases, Prevention, Rare Diseases, Clinical Research, Pancreatic Cancer, Good Health and Well Being, Adult, Black or African American, Age Factors, Aged, Aged, 80 and over, Carcinoma, Pancreatic Ductal, Comorbidity, Educational Status, Female, Health Status, Hispanic or Latino, Humans, Kaplan-Meier Estimate, Life Style, Logistic Models, Male, Mental Health, Middle Aged, Multivariate Analysis, Neoplasm Staging, Odds Ratio, Pancreatic Neoplasms, Proportional Hazards Models, Quality of Life, Risk Factors, Sex Factors, Surveys and Questionnaires, United States, White People, Quality of life, Pancreatic ductal adenocarcinoma, Overall survival, Prognostic indicator, Short Form-12, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundQuality of life (QOL) is impaired in pancreatic cancer patients. Our aim was to investigate the determinants and prognostic value of QOL after diagnosis in a hospital-based cohort of racially/ethnically diverse patients with pancreatic ductal adenocarcinoma (PDAC).Patients and methodsQOL was prospectively assessed using the Short Form-12 in 2478 PDAC patients. The Physical Component Summary (PCS) and Mental Component Summary (MCS) were categorised into tertiles based on their distribution. Ordered logistic regression was adopted to compare the risk of having lower PCS and MCS by patient sociodemographic and clinical characteristics. The association of PCS and MCS with mortality was assessed by Cox regression.ResultsCompared with non-Hispanic whites, Hispanics were at significantly higher risk of having lower PCS (odds ratio [95% CI], 1.69 [1.26-2.26]; P

Published
2018

7. Genome-wide association analysis identifies six new loci associated with forced vital capacity

Author

Loth, Daan W, Artigas, María Soler, Gharib, Sina A, Wain, Louise V, Franceschini, Nora, Koch, Beate, Pottinger, Tess D, Smith, Albert Vernon, Duan, Qing, Oldmeadow, Chris, Lee, Mi Kyeong, Strachan, David P, James, Alan L, Huffman, Jennifer E, Vitart, Veronique, Ramasamy, Adaikalavan, Wareham, Nicholas J, Kaprio, Jaakko, Wang, Xin-Qun, Trochet, Holly, Kähönen, Mika, Flexeder, Claudia, Albrecht, Eva, Lopez, Lorna M, de Jong, Kim, Thyagarajan, Bharat, Alves, Alexessander Couto, Enroth, Stefan, Omenaas, Ernst, Joshi, Peter K, Fall, Tove, Viñuela, Ana, Launer, Lenore J, Loehr, Laura R, Fornage, Myriam, Li, Guo, Wilk, Jemma B, Tang, Wenbo, Manichaikul, Ani, Lahousse, Lies, Harris, Tamara B, North, Kari E, Rudnicka, Alicja R, Hui, Jennie, Gu, Xiangjun, Lumley, Thomas, Wright, Alan F, Hastie, Nicholas D, Campbell, Susan, Kumar, Rajesh, Pin, Isabelle, Scott, Robert A, Pietiläinen, Kirsi H, Surakka, Ida, Liu, Yongmei, Holliday, Elizabeth G, Schulz, Holger, Heinrich, Joachim, Davies, Gail, Vonk, Judith M, Wojczynski, Mary, Pouta, Anneli, Johansson, Åsa, Wild, Sarah H, Ingelsson, Erik, Rivadeneira, Fernando, Völzke, Henry, Hysi, Pirro G, Eiriksdottir, Gudny, Morrison, Alanna C, Rotter, Jerome I, Gao, Wei, Postma, Dirkje S, White, Wendy B, Rich, Stephen S, Hofman, Albert, Aspelund, Thor, Couper, David, Smith, Lewis J, Psaty, Bruce M, Lohman, Kurt, Burchard, Esteban G, Uitterlinden, André G, Garcia, Melissa, Joubert, Bonnie R, McArdle, Wendy L, Musk, A Bill, Hansel, Nadia, Heckbert, Susan R, Zgaga, Lina, van Meurs, Joyce BJ, Navarro, Pau, Rudan, Igor, Oh, Yeon-Mok, Redline, Susan, Jarvis, Deborah L, Zhao, Jing Hua, Rantanen, Taina, O'Connor, George T, and Ripatti, Samuli

Subjects
Biological Sciences, Genetics, Human Genome, Rare Diseases, Lung, Cancer, Lung Cancer, Respiratory, Cohort Studies, Databases, Genetic, Follow-Up Studies, Forced Expiratory Volume, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Lung Diseases, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Prognosis, Quantitative Trait Loci, Respiratory Function Tests, Spirometry, Vital Capacity, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

Published
2014

8. Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia

Author

Simino, Jeannette, Shi, Gang, Bis, Joshua C, Chasman, Daniel I, Ehret, Georg B, Gu, Xiangjun, Guo, Xiuqing, Hwang, Shih-Jen, Sijbrands, Eric, Smith, Albert V, Verwoert, Germaine C, Bragg-Gresham, Jennifer L, Cadby, Gemma, Chen, Peng, Cheng, Ching-Yu, Corre, Tanguy, de Boer, Rudolf A, Goel, Anuj, Johnson, Toby, Khor, Chiea-Chuen, Study, LifeLines Cohort, Alizadeh, Behrooz Z, Boezen, H Marike, Bruinenberg, Marcel, Franke, Lude, van der Harst, Pim, Hillege, Hans L, van der Klauw, Melanie M, Navis, Gerjan, Ormel, Johan, Postma, Dirkje S, Rosmalen, Judith GM, Slaets, Joris P, Snieder, Harold, Stolk, Ronald P, Wolffenbuttel, Bruce HR, Wijmenga, Cisca, Lluís-Ganella, Carla, Luan, Jian’an, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Sim, Xueling, Sõber, Siim, van der Most, Peter J, Verweij, Niek, Zhao, Jing Hua, Amin, Najaf, Boerwinkle, Eric, Bouchard, Claude, Dehghan, Abbas, Eiriksdottir, Gudny, Elosua, Roberto, Franco, Oscar H, Gieger, Christian, Harris, Tamara B, Hercberg, Serge, Hofman, Albert, James, Alan L, Johnson, Andrew D, Kähönen, Mika, Khaw, Kay-Tee, Kutalik, Zoltan, Larson, Martin G, Launer, Lenore J, Li, Guo, Liu, Jianjun, Liu, Kiang, Morrison, Alanna C, Ong, Rick Twee-Hee, Papanicolau, George J, Penninx, Brenda W, Psaty, Bruce M, Raffel, Leslie J, Raitakari, Olli T, Rice, Kenneth, Rivadeneira, Fernando, Rose, Lynda M, Sanna, Serena, Scott, Robert A, Siscovick, David S, Uitterlinden, Andre G, Vaidya, Dhananjay, Vasan, Ramachandran S, Vithana, Eranga Nishanthie, Völker, Uwe, Völzke, Henry, Watkins, Hugh, Young, Terri L, Aung, Tin, Bochud, Murielle, Farrall, Martin, Hartman, Catharina A, Laan, Maris, Lakatta, Edward G, Lehtimäki, Terho, and Loos, Ruth JF

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Clinical Research, Human Genome, Aging, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Age Factors, Aged, Blood Pressure, Cohort Studies, Humans, Middle Aged, Young Adult, LifeLines Cohort Study, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ≤ 5 × 10(-8)) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10(-4)) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.

Published
2014

9. Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations

Author

Ganesh, Santhi K, Chasman, Daniel I, Larson, Martin G, Guo, Xiuqing, Verwoert, Germain, Bis, Joshua C, Gu, Xiangjun, Smith, Albert V, Yang, Min-Lee, Zhang, Yan, Ehret, Georg, Rose, Lynda M, Hwang, Shih-Jen, Papanicolau, George J, Sijbrands, Eric J, Rice, Kenneth, Eiriksdottir, Gudny, Pihur, Vasyl, Ridker, Paul M, Vasan, Ramachandran S, Newton-Cheh, Christopher, Consortium, Global Blood Pressure Genetics, Johnson, Toby, Gateva, Vesela, Tobin, Martin D, Bochud, Murielle, Coin, Lachlan, Najjar, Samer S, Zhao, Jing Hua, Heath, Simon C, Eyheramendy, Susana, Papadakis, Konstantinos, Voight, Benjamin F, Scott, Laura J, Zhang, Feng, Farrall, Martin, Tanaka, Toshiko, Wallace, Chris, Chambers, John C, Khaw, Kay-Tee, Nilsson, Peter, van der Harst, Pim, Polidoro, Silvia, Grobbee, Diederick E, Onland-Moret, N Charlotte, Bots, Michiel L, Wain, Louise V, Elliott, Katherine S, Teumer, Alexander, Luan, Jian’an, Lucas, Gavin, Kuusisto, Johanna, Burton, Paul R, Hadley, David, McArdle, Wendy L, Brown, Morris, Dominiczak, Anna, Newhouse, Stephen J, Samani, Nilesh J, Webster, John, Zeggini, Eleftheria, Beckmann, Jacques S, Bergmann, Sven, Lim, Noha, Song, Kijoung, Vollenweider, Peter, Waeber, Gerard, Waterworth, Dawn M, Yuan, Xin, Groop, Leif, Orho-Melander, Marju, Allione, Alessandra, Di Gregorio, Alessandra, Guarrera, Simonetta, Panico, Salvatore, Ricceri, Fulvio, Romanazzi, Valeria, Sacerdote, Carlotta, Vineis, Paolo, Barroso, Inês, Sandhu, Manjinder S, Luben, Robert N, Crawford, Gabriel J, Jousilahti, Pekka, Perola, Markus, Boehnke, Michael, Bonnycastle, Lori L, Collins, Francis S, Jackson, Anne U, Mohlke, Karen L, Stringham, Heather M, Valle, Timo T, Willer, Cristen J, Bergman, Richard N, Morken, Mario A, Döring, Angela, Gieger, Christian, Illig, Thomas, and Meitinger, Thomas

Subjects
Genetics, Human Genome, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Blood Pressure, Genome-Wide Association Study, Humans, Longitudinal Studies, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Global Blood Pressure Genetics Consortium, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Blood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations. We studied systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) averaged over multiple years in 46,629 individuals of European ancestry. We identified 39 trait-variant associations across 19 independent loci (p < 5 × 10(-8)); five associations (in four loci) uniquely identified by our LTA analyses included those of SBP and MAP at 2p23 (rs1275988, near KCNK3), DBP at 2q11.2 (rs7599598, in FER1L5), and PP at 6p21 (rs10948071, near CRIP3) and 7p13 (rs2949837, near IGFBP3). Replication analyses conducted in cohorts with single-visit BP data showed positive replication of associations and a nominal association (p < 0.05). We estimated a 20% gain in statistical power with long-term average (LTA) as compared to single-visit BP association studies. Using LTA analysis, we identified genetic loci influencing BP. LTA might be one way of increasing the power of genetic associations for continuous traits in extant samples for other phenotypes that are measured serially over time.

Published
2014

10. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

Author

Tang, Wenbo, Kowgier, Matthew, Loth, Daan W, Soler Artigas, María, Joubert, Bonnie R, Hodge, Emily, Gharib, Sina A, Smith, Albert V, Ruczinski, Ingo, Gudnason, Vilmundur, Mathias, Rasika A, Harris, Tamara B, Hansel, Nadia N, Launer, Lenore J, Barnes, Kathleen C, Hansen, Joyanna G, Albrecht, Eva, Aldrich, Melinda C, Allerhand, Michael, Barr, R Graham, Brusselle, Guy G, Couper, David J, Curjuric, Ivan, Davies, Gail, Deary, Ian J, Dupuis, Josée, Fall, Tove, Foy, Millennia, Franceschini, Nora, Gao, Wei, Gläser, Sven, Gu, Xiangjun, Hancock, Dana B, Heinrich, Joachim, Hofman, Albert, Imboden, Medea, Ingelsson, Erik, James, Alan, Karrasch, Stefan, Koch, Beate, Kritchevsky, Stephen B, Kumar, Ashish, Lahousse, Lies, Li, Guo, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Lohman, Kurt, Lumley, Thomas, McArdle, Wendy L, Meibohm, Bernd, Morris, Andrew P, Morrison, Alanna C, Musk, Bill, North, Kari E, Palmer, Lyle J, Probst-Hensch, Nicole M, Psaty, Bruce M, Rivadeneira, Fernando, Rotter, Jerome I, Schulz, Holger, Smith, Lewis J, Sood, Akshay, Starr, John M, Strachan, David P, Teumer, Alexander, Uitterlinden, André G, Völzke, Henry, Voorman, Arend, Wain, Louise V, Wells, Martin T, Wilk, Jemma B, Williams, O Dale, Heckbert, Susan R, Stricker, Bruno H, London, Stephanie J, Fornage, Myriam, Tobin, Martin D, O'Connor, George T, Hall, Ian P, and Cassano, Patricia A

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Human Genome, Lung, Clinical Research, Prevention, Respiratory, Adult, Chromosomes, Human, Pair 11, Female, Gene Expression Regulation, Genetic Loci, Genome-Wide Association Study, Humans, Longitudinal Studies, Male, Respiration, General Science & Technology
Abstract

BackgroundGenome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.MethodsWe performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.ResultsThe overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.ConclusionsIn this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

Published
2014

11. Risk stratification for hepatocellular cancer among patients with cirrhosis using a hepatic fat polygenic risk score

Author

Thrift, Aaron P., primary, Kanwal, Fasiha, additional, Liu, Yanhong, additional, Khaderi, Saira, additional, Singal, Amit G., additional, Marrero, Jorge A., additional, Loo, Nicole, additional, Asrani, Sumeet K., additional, Luster, Michelle, additional, Al-Sarraj, Abeer, additional, Ning, Jing, additional, Tsavachidis, Spiridon, additional, Gu, Xiangjun, additional, Amos, Christopher I., additional, and El-Serag, Hashem B., additional

Published
2023
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12. Risk factors for HCC in contemporary cohorts of patients with cirrhosis

Author

Kanwal, Fasiha, primary, Khaderi, Saira, additional, Singal, Amit G., additional, Marrero, Jorge A., additional, Loo, Nicole, additional, Asrani, Sumeet K., additional, Amos, Christopher I., additional, Thrift, Aaron P., additional, Gu, Xiangjun, additional, Luster, Michelle, additional, Al‐Sarraj, Abeer, additional, Ning, Jing, additional, and El‐Serag, Hashem B., additional

Published
2023
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13. EPID-03. PATHOGENIC GERMLINE MUTATIONS IN GLIOMA PATIENTS

Author

Mandel, Jacob, primary, Jalali, Ali, additional, Patel, Akash, additional, McDonald, Malcolm, additional, Prather, Lyndsey, additional, Helfer, Cassandra, additional, Gu, Xiangjun, additional, Ludmir, Ethan, additional, Echeverria, A J, additional, Rao, Ganesh, additional, Dhar, Shweta, additional, and Amos, Chris, additional

Published
2022
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16. 530: RISK STRATIFICATION MODEL FOR HEPATOCELLULAR CANCER IN PATIENTS WITH CIRRHOSIS

Author

Kanwal, Fasiha, primary, Khaderi, Saira, additional, Singal, Amit G., additional, Marrero, Jorge A., additional, Asrani, Sumeet K., additional, Loo, Nicole, additional, Amos, Christopher I., additional, Thrift, Aaron P., additional, Kramer, Jennifer R., additional, Gu, Xiangjun, additional, Luster, Michelle, additional, Alsarraj, Abeer, additional, Ning, Jing, additional, and El-Serag, Hashem B., additional

Published
2022
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20. X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

Author

Asselta, Rosanna, primary, Paraboschi, Elvezia M., additional, Gerussi, Alessio, additional, Cordell, Heather J., additional, Mells, George F., additional, Sandford, Richard N., additional, Jones, David E., additional, Nakamura, Minoru, additional, Ueno, Kazuko, additional, Hitomi, Yuki, additional, Kawashima, Minae, additional, Nishida, Nao, additional, Tokunaga, Katsushi, additional, Nagasaki, Masao, additional, Tanaka, Atsushi, additional, Tang, Ruqi, additional, Li, Zhiqiang, additional, Shi, Yongyong, additional, Liu, Xiangdong, additional, Xiong, Ma, additional, Hirschfield, Gideon, additional, Siminovitch, Katherine A., additional, Carbone, Marco, additional, Cardamone, Giulia, additional, Duga, Stefano, additional, Gershwin, M. Eric, additional, Seldin, Michael F., additional, Invernizzi, Pietro, additional, Walker, Erin, additional, Xie, Gang, additional, Mason, Andy, additional, Myers, Robert, additional, Peltekian, Kevork, additional, Ghent, Cameron, additional, Atkinson, Elizabeth, additional, Juran, Bruce, additional, Lazaridis, Kostas, additional, Lu, Yue, additional, Gu, Xiangjun, additional, Jing, Kaiyan, additional, Amos, Chris, additional, Affronti, Andrea, additional, Brunetto, Maurizia, additional, Coco, Barbara, additional, Spinzi, Giancarlo, additional, Elia, Gianfranco, additional, Ferrari, Carlo, additional, Lleo, Ana, additional, Muratori, Luigi, additional, Muratori, Paolo, additional, Portincasa, Piero, additional, Colli, Agostino, additional, Bruno, Savino, additional, Colloredo, Guido, additional, Azzaroli, Francesco, additional, Andreone, Pietro, additional, Bragazzi, MariaConsiglia, additional, Alvaro, Domenico, additional, Cardinale, Vincenzo, additional, Cazzagon, Nora, additional, Rigamonti, Cristina, additional, Floreani, Annarosa, additional, Rosina, Floriano, additional, Ciaccio, Antonio, additional, Cristoferi, Laura, additional, D’Amato, Daphne, additional, Malinverno, Federica, additional, Mancuso, Clara, additional, Massironi, Sara, additional, Milani, Chiara, additional, O’Donnell, Sarah E., additional, Ronca, Vincenzo, additional, Barisani, Donatella, additional, Lampertico, Pietro, additional, Donato, Francesca, additional, Fagiuoli, Stefano, additional, Almasio, Piero L., additional, Giannini, Edoardo, additional, Cursaro, Carmela, additional, Colombo, Massimo, additional, Valenti, Luca, additional, Miele, Luca, additional, Andriulli, Angelo, additional, Niro, Grazia A., additional, Grattagliano, Ignazio, additional, Morini, Lorenzo, additional, Casella, Giovanni, additional, Vinci, Maria, additional, Battezzati, Pier Maria, additional, Crosignani, Andrea, additional, Zuin, Massimo, additional, Mattalia, Alberto, additional, Calvaruso, Vincenza, additional, Colombo, Silvia, additional, Benedetti, Antonio, additional, Marzioni, Marco, additional, Galli, Andrea, additional, Marra, Fabio, additional, Tarocchi, Mirko, additional, Picciotto, Antonio, additional, Morisco, Filomena, additional, Fabris, Luca, additional, Crocè, Lory Saveria, additional, Tiribelli, Claudio, additional, Toniutto, Pierluigi, additional, Strazzabosco, Mario, additional, Ch’ng, Chin Lye, additional, Rahman, Mesbah, additional, Yapp, Tom, additional, Sturgess, Richard, additional, Healey, Christopher, additional, Czajkowski, Marek, additional, Gunasekera, Anton, additional, Gyawali, Pranab, additional, Premchand, Purushothaman, additional, Kapur, Kapil, additional, Marley, Richard, additional, Foster, Graham, additional, Watson, Alan, additional, Dias, Aruna, additional, Subhani, Javaid, additional, Harvey, Rory, additional, McCorry, Roger, additional, Ramanaden, David, additional, Gasem, Jaber, additional, Evans, Richard, additional, Mathialahan, Thiriloganathan, additional, Shorrock, Christopher, additional, Lipscomb, George, additional, Southern, Paul, additional, Tibble, Jeremy, additional, Gorard, David, additional, Palegwala, Altaf, additional, Jones, Susan, additional, Dawwas, Mohamed, additional, Alexander, Graeme, additional, Dolwani, Sunil, additional, Prince, Martin, additional, Foxton, Matthew, additional, Elphick, David, additional, Mitchison, Harriet, additional, Gooding, Ian, additional, Karmo, Mazn, additional, Saksena, Sushma, additional, Mendall, Mike, additional, Patel, Minesh, additional, Ede, Roland, additional, Austin, Andrew, additional, Sayer, Joanna, additional, Hankey, Lorraine, additional, Hovell, Christopher, additional, Fisher, Neil, additional, Carter, Martyn, additional, Koss, Konrad, additional, Piotrowicz, Andrzej, additional, Grimley, Charles, additional, Neal, David, additional, Lim, Guan, additional, Levi, Sass, additional, Ala, Aftab, additional, Broad, Andrea, additional, Saeed, Athar, additional, Wood, Gordon, additional, Brown, Jonathan, additional, Wilkinson, Mark, additional, Gordon, Harriet, additional, Ramage, John, additional, Ridpath, Jo, additional, Ngatchu, Theodore, additional, Grover, Bob, additional, Shaukat, Syed, additional, Shidrawi, Ray, additional, Abouda, George, additional, Ali, Faiz, additional, Rees, Ian, additional, Salam, Imroz, additional, Narain, Mark, additional, Brown, Ashley, additional, Taylor-Robinson, Simon, additional, Williams, Simon, additional, Grellier, Leonie, additional, Banim, Paul, additional, Das, Debasish, additional, Chilton, Andrew, additional, Heneghan, Michael, additional, Curtis, Howard, additional, Gess, Markus, additional, Drake, Ian, additional, Aldersley, Mark, additional, Davies, Mervyn, additional, Jones, Rebecca, additional, McNair, Alastair, additional, Srirajaskanthan, Raj, additional, Pitcher, Maxton, additional, Sen, Sambit, additional, Bird, George, additional, Barnardo, Adrian, additional, Kitchen, Paul, additional, Yoong, Kevin, additional, Chirag, Oza, additional, Sivaramakrishnan, Nurani, additional, MacFaul, George, additional, Jones, David, additional, Shah, Amir, additional, Evans, Chris, additional, Saha, Subrata, additional, Pollock, Katharine, additional, Bramley, Peter, additional, Mukhopadhya, Ashis, additional, Fraser, Andrew, additional, Mills, Peter, additional, Shallcross, Christopher, additional, Campbell, Stewart, additional, Bathgate, Andrew, additional, Shepherd, Alan, additional, Dillon, John, additional, Rushbrook, Simon, additional, Przemioslo, Robert, additional, Macdonald, Christopher, additional, Metcalf, Jane, additional, Shmueli, Udi, additional, Davis, Andrew, additional, Naqvi, Asifabbas, additional, Lee, Tom, additional, Ryder, Stephen D., additional, Collier, Jane, additional, Klass, Howard, additional, Ninkovic, Mary, additional, Cramp, Matthew, additional, Sharer, Nicholas, additional, Aspinall, Richard, additional, Goggin, Patrick, additional, Ghosh, Deb, additional, Douds, Andrew, additional, Hoeroldt, Barbara, additional, Booth, Jonathan, additional, Williams, Earl, additional, Hussaini, Hyder, additional, Stableforth, William, additional, Ayres, Reuben, additional, Thorburn, Douglas, additional, Marshall, Eileen, additional, Burroughs, Andrew, additional, Mann, Steven, additional, Lombard, Martin, additional, Richardson, Paul, additional, Patanwala, Imran, additional, Maltby, Julia, additional, Brookes, Matthew, additional, Mathew, Ray, additional, Vyas, Samir, additional, Singhal, Saket, additional, Gleeson, Dermot, additional, Misra, Sharat, additional, Butterworth, Jeff, additional, George, Keith, additional, Harding, Tim, additional, Douglass, Andrew, additional, Panter, Simon, additional, Shearman, Jeremy, additional, Bray, Gary, additional, Butcher, Graham, additional, Forton, Daniel, additional, Mclindon, John, additional, Cowan, Matthew, additional, Whatley, Gregory, additional, Mandal, Aditya, additional, Gupta, Hemant, additional, Sanghi, Pradeep, additional, Jain, Sanjiv, additional, Pereira, Steve, additional, Prasad, Geeta, additional, Watts, Gill, additional, Wright, Mark, additional, Neuberger, James, additional, Gordon, Fiona, additional, Unitt, Esther, additional, Grant, Allister, additional, Delahooke, Toby, additional, Higham, Andrew, additional, Brind, Alison, additional, Cox, Mark, additional, Ramakrishnan, Subramaniam, additional, King, Alistair, additional, Collins, Carole, additional, Whalley, Simon, additional, Li, Andy, additional, Fraser, Jocelyn, additional, Bell, Andrew, additional, Wong, Voi Shim, additional, Singhal, Amit, additional, Gee, Ian, additional, Ang, Yeng, additional, Ransford, Rupert, additional, Gotto, James, additional, Millson, Charles, additional, Bowles, Jane, additional, Thomas, Caradog, additional, Harrison, Melanie, additional, Galaska, Roman, additional, Kendall, Jennie, additional, Whiteman, Jessica, additional, Lawlor, Caroline, additional, Gray, Catherine, additional, Elliott, Keith, additional, Mulvaney-Jones, Caroline, additional, Hobson, Lucie, additional, Van Duyvenvoorde, Greta, additional, Loftus, Alison, additional, Seward, Katie, additional, Penn, Ruth, additional, Maiden, Jane, additional, Damant, Rose, additional, Hails, Janeane, additional, Cloudsdale, Rebecca, additional, Silvestre, Valeria, additional, Glenn, Sue, additional, Dungca, Eleanor, additional, Wheatley, Natalie, additional, Doyle, Helen, additional, Kent, Melanie, additional, Hamilton, Caroline, additional, Braim, Delyth, additional, Wooldridge, Helen, additional, Abrahams, Rachel, additional, Paton, Alison, additional, Lancaster, Nicola, additional, Gibbins, Andrew, additional, Hogben, Karen, additional, Desousa, Phillipa, additional, Muscariu, Florin, additional, Musselwhite, Janine, additional, McKay, Alexandra, additional, Tan, LaiTing, additional, Foale, Carole, additional, Brighton, Jacqueline, additional, Flahive, Kerry, additional, Nambela, Estelle, additional, Townshend, Paula, additional, Ford, Chris, additional, Holder, Sophie, additional, Palmer, Caroline, additional, Featherstone, James, additional, Nasseri, Mariam, additional, Sadeghian, Joy, additional, Williams, Bronwen, additional, Thomas, Carol, additional, Rolls, Sally-Ann, additional, Hynes, Abigail, additional, Duggan, Claire, additional, Jones, Sarah, additional, Crossey, Mary, additional, Stansfield, Glynis, additional, MacNicol, Carolyn, additional, Wilkins, Joy, additional, Wilhelmsen, Elva, additional, Raymode, Parizade, additional, Lee, Hye-Jeong, additional, Durant, Emma, additional, Bishop, Rebecca, additional, Ncube, Noma, additional, Tripoli, Sherill, additional, Casey, Rebecca, additional, Cowley, Caroline, additional, Miller, Richard, additional, Houghton, Kathryn, additional, Ducker, Samantha, additional, Wright, Fiona, additional, Bird, Bridget, additional, Baxter, Gwen, additional, Keggans, Janie, additional, Hughes, Maggie, additional, Grieve, Emma, additional, Young, Karin, additional, Williams, D., additional, Ocker, Kate, additional, Hines, Frances, additional, Martin, Kirsty, additional, Innes, Caron, additional, Valliani, Talal, additional, Fairlamb, Helen, additional, Thornthwaite, Sarah, additional, Eastick, Anne, additional, Tanqueray, Elizabeth, additional, Morrison, Jennifer, additional, Holbrook, Becky, additional, Browning, Julie, additional, Walker, Kirsten, additional, Congreave, Susan, additional, Verheyden, Juliette, additional, Slininger, Susan, additional, Stafford, Lizzie, additional, O’Donnell, Denise, additional, Ainsworth, Mark, additional, Lord, Susan, additional, Kent, Linda, additional, March, Linda, additional, Dickson, Christine, additional, Simpson, Diane, additional, Longhurst, Beverley, additional, Hayes, Maria, additional, Shpuza, Ervin, additional, White, Nikki, additional, Besley, Sarah, additional, Pearson, Sallyanne, additional, Wright, Alice, additional, Jones, Linda, additional, Gunter, Emma, additional, Dewhurst, Hannah, additional, Fouracres, Anna, additional, Farrington, Liz, additional, Graves, Lyn, additional, Marriott, Suzie, additional, Leoni, Marina, additional, Tyrer, David, additional, Martin, Kate, additional, Dali-kemmery, Lola, additional, Lambourne, Victoria, additional, Green, Marie, additional, Sirdefield, Dawn, additional, Amor, Kelly, additional, Colley, Julie, additional, Shinder, Bal, additional, Jones, Jayne, additional, Mills, Marisa, additional, Carnahan, Mandy, additional, Taylor, Natalie, additional, Boulton, Kerenza, additional, Tregonning, Julie, additional, Brown, Carly, additional, Clifford, Gayle, additional, Archer, Emily, additional, Hamilton, Maria, additional, Curtis, Janette, additional, Shewan, Tracey, additional, Walsh, Sue, additional, Warner, Karen, additional, Netherton, Kimberley, additional, Mupudzi, Mcdonald, additional, Gunson, Bridget, additional, Gitahi, Jane, additional, Gocher, Denise, additional, Batham, Sally, additional, Pateman, Hilary, additional, Desmennu, Senayon, additional, Conder, Jill, additional, Clement, Darren, additional, Gallagher, Susan, additional, Orpe, Jacky, additional, Chan, PuiChing, additional, Currie, Lynn, additional, O’Donohoe, Lynn, additional, Oblak, Metod, additional, Morgan, Lisa, additional, Quinn, Marie, additional, Amey, Isobel, additional, Baird, Yolanda, additional, Cotterill, Donna, additional, Cumlat, Lourdes, additional, Winter, Louise, additional, Greer, Sandra, additional, Spurdle, Katie, additional, Allison, Joanna, additional, Dyer, Simon, additional, Sweeting, Helen, additional, Kordula, Jean, additional, Aiba, Yoshihiro, additional, Nakamura, Hitomi, additional, Abiru, Seigo, additional, Nagaoka, Shinya, additional, Komori, Atsumasa, additional, Yatsuhashi, Hiroshi, additional, Ishibashi, Hiromi, additional, Ito, Masahiro, additional, Kawai, Yosuke, additional, Kohn, Seik-Soon, additional, Gervais, Olivier, additional, Migita, Kiyoshi, additional, Katsushima, Shinji, additional, Naganuma, Atsushi, additional, Sugi, Kazuhiro, additional, Komatsu, Tatsuji, additional, Mannami, Tomohiko, additional, Matsushita, Kouki, additional, Yoshizawa, Kaname, additional, Makita, Fujio, additional, Nikami, Toshiki, additional, Nishimura, Hideo, additional, Kouno, Hiroshi, additional, Kouno, Hirotaka, additional, Ota, Hajime, additional, Komura, Takuya, additional, Nakamura, Yoko, additional, Shimada, Masaaki, additional, Hirashima, Noboru, additional, Komeda, Toshiki, additional, Ario, Keisuke, additional, Nakamuta, Makoto, additional, Yamashita, Tsutomu, additional, Furuta, Kiyoshi, additional, Kikuchi, Masahiro, additional, Naeshiro, Noriaki, additional, Takahashi, Hironao, additional, Mano, Yutaka, additional, Tsunematsu, Seiji, additional, Yabuuchi, Iwao, additional, Shimada, Yusuke, additional, Yamauchi, Kazuhiko, additional, Sugimoto, Rie, additional, Sakai, Hironori, additional, Mita, Eiji, additional, Koda, Masaharu, additional, Tsuruta, Satoru, additional, Kamitsukasa, Hiroshi, additional, Sato, Takeaki, additional, Masaki, Naohiko, additional, Kobata, Tatsuro, additional, Fukushima, Nobuyoshi, additional, Higuchi, Nobito, additional, Ohara, Yukio, additional, Muro, Toyokichi, additional, Takesaki, Eiichi, additional, Takaki, Hitoshi, additional, Yamamoto, Tetsuo, additional, Kato, Michio, additional, Nagaoki, Yuko, additional, Hayashi, Shigeki, additional, Ishida, Jinya, additional, Watanabe, Yukio, additional, Kobayashi, Masakazu, additional, Koga, Michiaki, additional, Saoshiro, Takeo, additional, Yagura, Michiyasu, additional, Hirata, Keisuke, additional, Takikawa, Hajime, additional, Ohira, Hiromasa, additional, Zeniya, Mikio, additional, Abe, Masanori, additional, Onji, Morikazu, additional, Kaneko, Shuichi, additional, Honda, Masao, additional, Arai, Kuniaki, additional, Arinaga-Hino, Teruko, additional, Hashimoto, Etsuko, additional, Taniai, Makiko, additional, Umemura, Takeji, additional, Joshita, Satoru, additional, Nakao, Kazuhiko, additional, Ichikawa, Tatsuki, additional, Shibata, Hidetaka, additional, Yamagiwa, Satoshi, additional, Seike, Masataka, additional, Honda, Koichi, additional, Sakisaka, Shotaro, additional, Takeyama, Yasuaki, additional, Harada, Masaru, additional, Senju, Michio, additional, Yokosuka, Osamu, additional, Kanda, Tatsuo, additional, Ueno, Yoshiyuki, additional, Kikuchi, Kentaro, additional, Ebinuma, Hirotoshi, additional, Himoto, Takashi, additional, Yasunami, Michio, additional, Murata, Kazumoto, additional, Mizokami, Masashi, additional, Shimoda, Shinji, additional, Miyake, Yasuhiro, additional, Takaki, Akinobu, additional, Yamamoto, Kazuhide, additional, Hirano, Katsuji, additional, Ichida, Takafumi, additional, Ido, Akio, additional, Tsubouchi, Hirohito, additional, Chayama, Kazuaki, additional, Harada, Kenichi, additional, Nakanuma, Yasuni, additional, Maehara, Yoshihiko, additional, Taketomi, Akinobu, additional, Shirabe, Ken, additional, Soejima, Yuji, additional, Mori, Akira, additional, Yagi, Shintaro, additional, Uemoto, Shinji, additional, Tanaka, Tomohiro, additional, Yamashiki, Noriyo, additional, Tamura, Sumito, additional, Sugawara, Yasuhiro, additional, and Kokudo, Norihiro, additional

Published
2021
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22. Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants

Author

Hirschfield, Gideon M., Liu, Xiangdong, Xu, Chun, Lu, Yue, Xie, Gang, Lu, Yan, Gu, Xiangjun, Walker, Erin J., Jing, Kaiyan, Juran, Brian D., Mason, Andrew L., Myers, Robert P., Peltekian, Kevork M., Ghent, Cameron N., Coltescu, Catalina, Atkinson, Elizabeth J., Heathcote, E. Jenny, Amos, Christopher I., Siminovitch; Katherine A., and Lazaridis, Konstantinos N.

Subjects
United Kingdom
Abstract

A study was conducted to investigate the genetic basis of primary biliary cirrhosis and the loci associated with it. Results indicated a significant connection between the cirrhosis and the HLA, IL12A, and IL12RB2 loci and the possibility that modulation of signaling by interleukin-12 and its receptor could prove beneficial in the treatment of this ailment.

Published
2009

28. Bayesian Approach to Understand the Association Between Treatment Down-staging and Survival for Patients With Pancreatic Adenocarcinoma.

Author

da Costa, Wilson Luiz Jr., Tran Cao, Hop S., Gu, Xiangjun, and Massarweh, Nader N.

Abstract

Objective: To evaluate the association between staging concordance, treatment sequencing, and response to neoadjuvant therapy (NAT) on the survival of patients with pancreatic ductal adenocarcinoma (PDAC). Summary of Background Data: NAT is increasingly utilized in the management of patients with PDAC, but it is unclear whether its benefit is contingent on tumor down-staging. Methods: This was a cohort study of stage I-III PDAC patients in the National Cancer Database (2006-2015) treated with upfront resection or NAT followed by surgery. We determined staging concordance using patients' clinical and pathological staging data. For NAT patients, we used Bayesian analysis to ascertain staging concordance accounting for down-staging. Results: Among 16,597 patients treated at 979 hospitals, 13,982 had an upfront resection and 2,615 NAT followed by surgery. Overall survival (OS) at 5-years ranged from 26.0% (95% CI 24.9%-27.1%) among cT1-2N0 patients to 18.6% (17.9%-19.2%) among cT1-3N+ ones. Patients with cT3-4 or cN+ tumors had improved OS after NAT compared to upfront surgery (all p< 0.001), while there was no difference among patients with cT1-2N0 (P = 0.16) disease. Relative to accurately staged cT1-2-3N+ or cT4 patients treated with upfront surgery, NAT was associated with a lower risk of death [HR 0.46 (0.37-0.57) for N+; HR 0.56 (0.40-0.77) for T4 disease], even among those without tumor down-staging [HR 0.81 (0.73-0.90) for N+; HR 0.48 (0.39-0.60) for T4]. Conclusions: NAT is associated with improved survival for PDAC, particularly for patients with more advanced disease and regardless of down-staging. Consideration should be given to recommending NAT for all PDAC patients. [ABSTRACT FROM AUTHOR]

Published
2022
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42. Aspirin, NSAIDs, and Glioma Risk: Original Data from the Glioma International Case–Control Study and a Meta-analysis

Author

Amirian, E. Susan, primary, Ostrom, Quinn T., additional, Armstrong, Georgina N., additional, Lai, Rose K., additional, Gu, Xiangjun, additional, Jacobs, Daniel I., additional, Jalali, Ali, additional, Claus, Elizabeth B., additional, Barnholtz-Sloan, Jill S., additional, Il'yasova, Dora, additional, Schildkraut, Joellen M., additional, Ali-Osman, Francis, additional, Sadetzki, Siegal, additional, Jenkins, Robert B., additional, Lachance, Daniel H., additional, Olson, Sara H., additional, Bernstein, Jonine L., additional, Merrell, Ryan T., additional, Wrensch, Margaret R., additional, Johansen, Christoffer, additional, Houlston, Richard S., additional, Scheurer, Michael E., additional, Shete, Sanjay, additional, Amos, Christopher I., additional, Melin, Beatrice, additional, and Bondy, Melissa L., additional

Published
2019
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43. Elucidating the molecular pathogenesis of glioma: integrated germline and somatic profiling of a familial glioma case series

Author

Jacobs, Daniel I, primary, Fukumura, Kazutaka, additional, Bainbridge, Matthew N, additional, Armstrong, Georgina N, additional, Tsavachidis, Spiridon, additional, Gu, Xiangjun, additional, Doddapaneni, Harsha V, additional, Hu, Jianhong, additional, Jayaseelan, Joy C, additional, Muzny, Donna M, additional, Huse, Jason T, additional, and Bondy, Melissa L, additional

Published
2018
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44. Abstract 3011: Determinants and prognostic value of quality of life in patients with pancreatic ductal adenocarcinoma

Author

Deng, Yang, primary, Tu, Huakang, additional, Pierzynski, Jeanne A., additional, Miller, Ethan, additional, Huang, Maosheng, additional, Gu, Xiangjun, additional, Chang, David W., additional, Ye, Yuanqing, additional, Hildebrandt, Michelle A., additional, Klein, Alison P., additional, Lippman, Scott M., additional, and Wu, Xifeng, additional

Published
2018
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45. Determinants and prognostic value of quality of life in patients with pancreatic ductal adenocarcinoma

Author

Deng, Yang, primary, Tu, Huakang, additional, Pierzynski, Jeanne A., additional, Miller, Ethan D., additional, Gu, Xiangjun, additional, Huang, Maosheng, additional, Chang, David W., additional, Ye, Yuanqing, additional, Hildebrandt, Michelle A.T., additional, Klein, Alison P., additional, Zhao, Ren, additional, Lippman, Scott M., additional, and Wu, Xifeng, additional

Published
2018
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46. Abstract LB-165: Personalized prognostic prediction models for breast cancer recurrence and survival incorporating multidimensional data

Author

Wu, Xifeng, primary, Ye, Yuanqing, additional, Barcenas, Carlos H., additional, Chow, Wong-Ho, additional, Meng, Qing H., additional, Gregor, Mariana Chavez Mac, additional, Hildebrandt, Michelle, additional, Zhao, Hua, additional, Gu, Xiangjun, additional, Deng, Yang, additional, Wagar, Elizabeth A., additional, Esteva, Francisco J., additional, Tripathy, Debu, additional, and Hortobagyi, Gabriel N., additional

Published
2017
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47. Personalized Prognostic Prediction Models for Breast Cancer Recurrence and Survival Incorporating Multidimensional Data

Author

Wu, Xifeng, primary, Ye, Yuanqing, additional, Barcenas, Carlos H., additional, Chow, Wong-Ho, additional, Meng, Qing H., additional, Chavez-MacGregor, Mariana, additional, Hildebrandt, Michelle A. T., additional, Zhao, Hua, additional, Gu, Xiangjun, additional, Deng, Yang, additional, Wagar, Elizabeth, additional, Esteva, Francisco J., additional, Tripathy, Debu, additional, and Hortobagyi, Gabriel N., additional

Published
2017
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50. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

Author

Chen, Lin, Tang, Wenbo, Kowgier, Matthew, Loth, Daan W., Joubert, Bonnie R., Hodge, Emily, Gharib, Sina A., Smith, Albert V., Ruczinski, Ingo, Gudnason, Vilmundur, Mathias, Rasika A., Harris, Tamara B., Hansel, Nadia N., Launer, Lenore J., Barnes, Kathleen C., Hansen, Joyanna G., Albrecht, Eva, Aldrich, Melinda C., Allerhand, Michael, Barr, R. Graham, Brusselle, Guy G., Couper, David J., Curjuric, Ivan, Davies, Gail, Deary, Ian J., Fall, Tove, Foy, Millennia, Franceschini, Nora, Gao, Wei, Gu, Xiangjun, Hancock, Dana B., Heinrich, Joachim, Hofman, Albert, Imboden, Medea, Ingelsson, Erik, James, Alan, Karrasch, Stefan, Koch, Beate, Kritchevsky, Stephen B., Kumar, Ashish, Lahousse, Lies, Li, Guo, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Lohman, Kurt, Lumley, Thomas, McArdle, Wendy L., Meibohm, Bernd, Morris, Andrew P., Morrison, Alanna C., Musk, Bill, North, Kari E., Palmer, Lyle J., Probst-Hensch, Nicole M., Psaty, Bruce M., Rivadeneira, Fernando, Rotter, Jerome I., Schulz, Holger, Smith, Lewis J., Sood, Akshay, Starr, John M., Strachan, David P., Teumer, Alexander, Voorman, Arend, Wain, Louise V., Wells, Martin T., Wilk, Jemma B., Williams, O. Dale, Heckbert, Susan R., Stricker, Bruno H., London, Stephanie J., Fornage, Myriam, Tobin, Martin D., O?Connor, George T., Hall, Ian P., Cassano, Patricia A., and Chen, Lin

Abstract

Background: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.Methods: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.Results: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 6 10-7). In addition, meta-analysis using the five cohorts with $3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18610-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.Conclusions: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

Published
2014

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