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2,931 results on '"Gaziano, J. Michael"'

1. Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program

Author

Verma, Anurag, Huffman, Jennifer E, Rodriguez, Alex, Conery, Mitchell, Liu, Molei, Ho, Yuk-Lam, Kim, Youngdae, Heise, David A, Guare, Lindsay, Panickan, Vidul Ayakulangara, Garcon, Helene, Linares, Franciel, Costa, Lauren, Goethert, Ian, Tipton, Ryan, Honerlaw, Jacqueline, Davies, Laura, Whitbourne, Stacey, Cohen, Jeremy, Posner, Daniel C, Sangar, Rahul, Murray, Michael, Wang, Xuan, Dochtermann, Daniel R, Devineni, Poornima, Shi, Yunling, Nandi, Tarak Nath, Assimes, Themistocles L, Brunette, Charles A, Carroll, Robert J, Clifford, Royce, Duvall, Scott, Gelernter, Joel, Hung, Adriana, Iyengar, Sudha K, Joseph, Jacob, Kember, Rachel, Kranzler, Henry, Kripke, Colleen M, Levey, Daniel, Luoh, Shiuh-Wen, Merritt, Victoria C, Overstreet, Cassie, Deak, Joseph D, Grant, Struan FA, Polimanti, Renato, Roussos, Panos, Shakt, Gabrielle, Sun, Yan V, Tsao, Noah, Venkatesh, Sanan, Voloudakis, Georgios, Justice, Amy, Begoli, Edmon, Ramoni, Rachel, Tourassi, Georgia, Pyarajan, Saiju, Tsao, Philip, O'Donnell, Christopher J, Muralidhar, Sumitra, Moser, Jennifer, Casas, Juan P, Bick, Alexander G, Zhou, Wei, Cai, Tianxi, Voight, Benjamin F, Cho, Kelly, Gaziano, J Michael, Madduri, Ravi K, Damrauer, Scott, and Liao, Katherine P

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, 2.1 Biological and endogenous factors, Mental health, Humans, Male, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Longitudinal Studies, Polymorphism, Single Nucleotide, Quantitative Trait Loci, United States, United States Department of Veterans Affairs, Veterans, Female, General Science & Technology
Abstract

One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program, a longitudinal study of diverse United States Veterans. Systematic analysis revealed 13,672 genomic risk loci; 1608 were only significant after including non-European populations. Fine-mapping identified causal variants at 6318 signals across 613 traits. One-third (n = 2069) were identified in participants from non-European populations. This reveals a broadly similar genetic architecture across populations, highlights genetic insights gained from underrepresented groups, and presents an extensive atlas of genetic associations.

Published
2024

3. Correlates of suicidal behaviors and genetic risk among United States veterans with schizophrenia or bipolar I disorder

Author

Bigdeli, Tim B., Barr, Peter B., Rajeevan, Nallakkandi, Graham, David P., Li, Yuli, Meyers, Jacquelyn L., Gorman, Bryan R., Peterson, Roseann E., Sayward, Frederick, Radhakrishnan, Krishnan, Natarajan, Sundar, Nielsen, David A., Wilkinson, Anna V., Malhotra, Anil K., Zhao, Hongyu, Brophy, Mary, Shi, Yunling, O’Leary, Timothy J., Gleason, Theresa, Przygodzki, Ronald, Pyarajan, Saiju, Muralidhar, Sumitra, Gaziano, J. Michael, Huang, Grant D., Concato, John, Siever, Larry J., DeLisi, Lynn E., Kimbrel, Nathan A., Beckham, Jean C., Swann, Alan C., Kosten, Thomas R., Fanous, Ayman H., Aslan, Mihaela, and Harvey, Philip D.

Published
2024
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4. Agent orange exposure and prostate cancer risk in the million veteran program

Author

Pagadala, Meghana S, Lui, Asona J, Zhong, Allison Y, Lynch, Julie A, Karunamuni, Roshan, Lee, Kyung Min, Plym, Anna, Rose, Brent S, Carter, Hannah K, Kibel, Adam S, DuVall, Scott L, Gaziano, J Michael, Panizzon, Matthew S, Hauger, Richard L, and Seibert, Tyler M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prostate Cancer, Cancer, Urologic Diseases, Humans, Male, Agent Orange, Prostatic Neoplasms, Veterans, Middle Aged, Aged, Vietnam Conflict, United States, Defoliants, Chemical, Risk Factors, 2, 4, 5-Trichlorophenoxyacetic Acid, 2, 4-Dichlorophenoxyacetic Acid, Polychlorinated Dibenzodioxins, prostate cancer, MVP, race/ ethnicity, health disparities, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundThe US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk.Patients and methodsParticipants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models.Results and interpretationOn univariable analysis, exposure to Agent Orange was not associated with increased PCa (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.06), metastatic PCa (HR: 0.98, 95% CI: 0.91-1.05, p = 0.55), or fatal PCa (HR: 0.94, 95% CI: 0.79-1.09, p = 0.41). When accounting for race/ethnicity and family history, Agent Orange exposure was independently associated with slightly increased risk of PCa (HR: 1.06, 95% CI: 1.04-1.09,

Published
2024

7. A multi-ancestry GWAS of Fuchs corneal dystrophy highlights the contributions of laminins, collagen, and endothelial cell regulation

Author

Gorman, Bryan R., Francis, Michael, Nealon, Cari L., Halladay, Christopher W., Duro, Nalvi, Markianos, Kyriacos, Genovese, Giulio, Hysi, Pirro G., Choquet, Hélène, Afshari, Natalie A., Li, Yi-Ju, Gaziano, J. Michael, Hung, Adriana M., Wu, Wen-Chih, Greenberg, Paul B., Pyarajan, Saiju, Lass, Jonathan H., Peachey, Neal S., and Iyengar, Sudha K.

Published
2024
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10. LATTE: Label-efficient Incident Phenotyping from Longitudinal Electronic Health Records

Author

Wen, Jun, Hou, Jue, Bonzel, Clara-Lea, Zhao, Yihan, Castro, Victor M., Gainer, Vivian S., Weisenfeld, Dana, Cai, Tianrun, Ho, Yuk-Lam, Panickan, Vidul A., Costa, Lauren, Hong, Chuan, Gaziano, J. Michael, Liao, Katherine P., Lu, Junwei, Cho, Kelly, and Cai, Tianxi

Subjects
Computer Science - Artificial Intelligence
Abstract

Electronic health record (EHR) data are increasingly used to support real-world evidence (RWE) studies. Yet its ability to generate reliable RWE is limited by the lack of readily available precise information on the timing of clinical events such as the onset time of heart failure. We propose a LAbel-efficienT incidenT phEnotyping (LATTE) algorithm to accurately annotate the timing of clinical events from longitudinal EHR data. By leveraging the pre-trained semantic embedding vectors from large-scale EHR data as prior knowledge, LATTE selects predictive EHR features in a concept re-weighting module by mining their relationship to the target event and compresses their information into longitudinal visit embeddings through a visit attention learning network. LATTE employs a recurrent neural network to capture the sequential dependency between the target event and visit embeddings before/after it. To improve label efficiency, LATTE constructs highly informative longitudinal silver-standard labels from large-scale unlabeled patients to perform unsupervised pre-training and semi-supervised joint training. Finally, LATTE enhances cross-site portability via contrastive representation learning. LATTE is evaluated on three analyses: the onset of type-2 diabetes, heart failure, and the onset and relapses of multiple sclerosis. We use various evaluation metrics present in the literature including the $ABC_{gain}$, the proportion of reduction in the area between the observed event indicator and the predicted cumulative incidences in reference to the prediction per incident prevalence. LATTE consistently achieves substantial improvement over benchmark methods such as SAMGEP and RETAIN in all settings., Comment: ERHs data

Published
2023

11. Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference

Author

Meng, Xiangrui, Navoly, Georgina, Giannakopoulou, Olga, Levey, Daniel F., Koller, Dora, Pathak, Gita A., Koen, Nastassja, Lin, Kuang, Adams, Mark J., Rentería, Miguel E., Feng, Yanzhe, Gaziano, J. Michael, Stein, Dan J., Zar, Heather J., Campbell, Megan L., van Heel, David A., Trivedi, Bhavi, Finer, Sarah, McQuillin, Andrew, Bass, Nick, Chundru, V. Kartik, Martin, Hilary C., Huang, Qin Qin, Valkovskaya, Maria, Chu, Chia-Yi, Kanjira, Susan, Kuo, Po-Hsiu, Chen, Hsi-Chung, Tsai, Shih-Jen, Liu, Yu-Li, Kendler, Kenneth S., Peterson, Roseann E., Cai, Na, Fang, Yu, Sen, Srijan, Scott, Laura J., Burmeister, Margit, Loos, Ruth J. F., Preuss, Michael H., Actkins, Ky’Era V., Davis, Lea K., Uddin, Monica, Wani, Agaz H., Wildman, Derek E., Aiello, Allison E., Ursano, Robert J., Kessler, Ronald C., Kanai, Masahiro, Okada, Yukinori, Sakaue, Saori, Rabinowitz, Jill A., Maher, Brion S., Uhl, George, Eaton, William, Cruz-Fuentes, Carlos S., Martinez-Levy, Gabriela A., Campos, Adrian I., Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wassertheil-Smoller, Sylvia, Jiang, Yunxuan, Tian, Chao, Martin, Nicholas G., Mitchell, Brittany L., Byrne, Enda M., Awasthi, Swapnil, Coleman, Jonathan R. I., Ripke, Stephan, Sofer, Tamar, Walters, Robin G., McIntosh, Andrew M., Polimanti, Renato, Dunn, Erin C., Stein, Murray B., Gelernter, Joel, Lewis, Cathryn M., and Kuchenbaecker, Karoline

Published
2024
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12. Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals

Author

Zhou, Hang, Kember, Rachel L., Deak, Joseph D., Xu, Heng, Toikumo, Sylvanus, Yuan, Kai, Lind, Penelope A., Farajzadeh, Leila, Wang, Lu, Hatoum, Alexander S., Johnson, Jessica, Lee, Hyunjoon, Mallard, Travis T., Xu, Jiayi, Johnston, Keira J. A., Johnson, Emma C., Nielsen, Trine Tollerup, Galimberti, Marco, Dao, Cecilia, Levey, Daniel F., Overstreet, Cassie, Byrne, Enda M., Gillespie, Nathan A., Gordon, Scott, Hickie, Ian B., Whitfield, John B., Xu, Ke, Zhao, Hongyu, Huckins, Laura M., Davis, Lea K., Sanchez-Roige, Sandra, Madden, Pamela A. F., Heath, Andrew C., Medland, Sarah E., Martin, Nicholas G., Ge, Tian, Smoller, Jordan W., Hougaard, David M., Børglum, Anders D., Demontis, Ditte, Krystal, John H., Gaziano, J. Michael, Edenberg, Howard J., Agrawal, Arpana, Justice, Amy C., Stein, Murray B., Kranzler, Henry R., and Gelernter, Joel

Published
2023
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13. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

Author

Wang, Anqi, Shen, Jiayi, Rodriguez, Alex A., Saunders, Edward J., Chen, Fei, Janivara, Rohini, Darst, Burcu F., Sheng, Xin, Xu, Yili, Chou, Alisha J., Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Plym, Anna, Sahimi, Ali, Hoffman, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Laisk, Triin, Figuerêdo, Jéssica, Muir, Kenneth, Ito, Shuji, Liu, Xiaoxi, Uchio, Yuji, Kubo, Michiaki, Kamatani, Yoichiro, Lophatananon, Artitaya, Wan, Peggy, Andrews, Caroline, Lori, Adriana, Choudhury, Parichoy P., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher T., Cho, Kelly, Mcmahon, Benjamin H., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Røder, Andreas, Stroomberg, Hein V., Batra, Jyotsna, Chambers, Suzanne, Horvath, Lisa, Clements, Judith A., Tilly, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordstrom, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie, Cook, Michael B., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Jr., Ian M., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L., Ostrander, Elaine A., Koutros, Stella, Beane Freeman, Laura E., Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Geraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Butler, Ebonee N., Mohler, James L., Taylor, Jack A., Kogevinas, Manolis, Dierssen-Sotos, Trinidad, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Pilie, Patrick, Yu, Yao, Bohlender, Ryan J., Gu, Jian, Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Brenner, Hermann, Chen, Xuechen, Holleczek, Bernd, Schöttker, Ben, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine M., Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Abraham, Aswin, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer, Petrovics, Gyorgy, Casey, Graham, Wang, Ying, Tettey, Yao, Lachance, Joseph, Tang, Wei, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Yamoah, Kosj, Govindasami, Koveela, Chokkalingam, Anand P., Keaton, Jacob M., Hellwege, Jacklyn N., Clark, Peter E., Jalloh, Mohamed, Gueye, Serigne M., Niang, Lamine, Ogunbiyi, Olufemi, Shittu, Olayiwola, Amodu, Olukemi, Adebiyi, Akindele O., Aisuodionoe-Shadrach, Oseremen I., Ajibola, Hafees O., Jamda, Mustapha A., Oluwole, Olabode P., Nwegbu, Maxwell, Adusei, Ben, Mante, Sunny, Darkwa-Abrahams, Afua, Diop, Halimatou, Gundell, Susan M., Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Kachuri, Linda, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Preuss, Michael H., Loos, Ruth J. F., Zawistowski, Matthew, Zöllner, Sebastian, Lu, Zeyun, Van Den Eeden, Stephen K., Easton, Douglas F., Ambs, Stefan, Edwards, Todd L., Mägi, Reedik, Rebbeck, Timothy R., Fritsche, Lars, Chanock, Stephen J., Berndt, Sonja I., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Gaziano, J. Michael, Justice, Amy C., Mancuso, Nick, Terao, Chikashi, Eeles, Rosalind A., Kote-Jarai, Zsofia, Madduri, Ravi K., Conti, David V., and Haiman, Christopher A.

Published
2023
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14. Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications

Author

Levey, Daniel F., Galimberti, Marco, Deak, Joseph D., Wendt, Frank R., Bhattacharya, Arjun, Koller, Dora, Harrington, Kelly M., Quaden, Rachel, Johnson, Emma C., Gupta, Priya, Biradar, Mahantesh, Lam, Max, Cooke, Megan, Rajagopal, Veera M., Empke, Stefany L. L., Zhou, Hang, Nunez, Yaira Z., Kranzler, Henry R., Edenberg, Howard J., Agrawal, Arpana, Smoller, Jordan W., Lencz, Todd, Hougaard, David M., Børglum, Anders D., Demontis, Ditte, Gaziano, J. Michael, Gandal, Michael J., Polimanti, Renato, Stein, Murray B., and Gelernter, Joel

Published
2023
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15. Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program

Author

Pagadala, Meghana S, Lynch, Julie, Karunamuni, Roshan, Alba, Patrick R, Lee, Kyung Min, Agiri, Fatai Y, Anglin, Tori, Carter, Hannah, Gaziano, J Michael, Jasuja, Guneet Kaur, Deka, Rishi, Rose, Brent S, Panizzon, Matthew S, Hauger, Richard L, and Seibert, Tyler M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prevention, Prostate Cancer, Cancer, Urologic Diseases, Clinical Research, Genetics, Aging, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Humans, Male, Aged, Prostatic Neoplasms, Veterans, Retrospective Studies, Prostate-Specific Antigen, Cohort Studies, Early Detection of Cancer, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundGenetic scores may provide an objective measure of prostate cancer risk and thus inform screening decisions. We evaluated whether a polygenic hazard score based on 290 genetic variants (PHS290) is associated with prostate cancer risk in a diverse population, including Black men, who have higher average risk of prostate cancer death but are often treated as a homogeneously high-risk group.MethodsThis was a retrospective analysis of the Million Veteran Program, a national, population-based cohort study of US military veterans conducted 2011-2021. Cox proportional hazards analyses tested for association of genetic and other risk factors (including self-reported race and ethnicity and family history) with age at death from prostate cancer, age at diagnosis of metastatic (nodal or distant) prostate cancer, and age at diagnosis of any prostate cancer.ResultsA total of 590 750 male participants were included. Median age at last follow-up was 69 years. PHS290 was associated with fatal prostate cancer in the full cohort and for each racial and ethnic group (P

Published
2023

16. Design and pilot results from the Million Veteran Program Return Of Actionable Results (MVP-ROAR) Study

Author

Vassy, Jason L., Brunette, Charles A., Yi, Thomas, Harrison, Alicia, Cardellino, Mark P., Assimes, Themistocles L., Christensen, Kurt D., Devineni, Poornima, Gaziano, J. Michael, Gong, Xin, Hui, Qin, Knowles, Joshua W., Muralidhar, Sumitra, Natarajan, Pradeep, Pyarajan, Saiju, Sears, Mary Gavin, Shi, Yunling, Sturm, Amy C., Whitbourne, Stacey B., Sun, Yan V., and Danowski, Morgan E.

Published
2024
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17. Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries

Author

Li, Chunxiao, Bishop, Tom R P, Imamura, Fumiaki, Sharp, Stephen J, Pearce, Matthew, Brage, Soren, Ong, Ken K, Ahsan, Habibul, Bes-Rastrollo, Maira, Beulens, Joline W J, den Braver, Nicole, Byberg, Liisa, Canhada, Scheine, Chen, Zhengming, Chung, Hsin-Fang, Cortés-Valencia, Adrian, Djousse, Luc, Drouin-Chartier, Jean-Philippe, Du, Huaidong, Du, Shufa, Duncan, Bruce B, Gaziano, J Michael, Gordon-Larsen, Penny, Goto, Atsushi, Haghighatdoost, Fahimeh, Härkänen, Tommi, Hashemian, Maryam, Hu, Frank B, Ittermann, Till, Järvinen, Ritva, Kakkoura, Maria G, Neelakantan, Nithya, Knekt, Paul, Lajous, Martin, Li, Yanping, Magliano, Dianna J, Malekzadeh, Reza, Le Marchand, Loic, Marques-Vidal, Pedro, Martinez-Gonzalez, Miguel A, Maskarinec, Gertraud, Mishra, Gita D, Mohammadifard, Noushin, O'Donoghue, Gráinne, O'Gorman, Donal, Popkin, Barry, Poustchi, Hossein, Sarrafzadegan, Nizal, Sawada, Norie, Schmidt, Maria Inês, Shaw, Jonathan E, Soedamah-Muthu, Sabita, Stern, Dalia, Tong, Lin, van Dam, Rob M, Völzke, Henry, Willett, Walter C, Wolk, Alicja, Yu, Canqing, Forouhi, Nita G, and Wareham, Nicholas J

Published
2024
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19. A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation

Author

Vujkovic, Marijana, Ramdas, Shweta, Lorenz, Kim M, Guo, Xiuqing, Darlay, Rebecca, Cordell, Heather J, He, Jing, Gindin, Yevgeniy, Chung, Chuhan, Myers, Robert P, Schneider, Carolin V, Park, Joseph, Lee, Kyung Min, Serper, Marina, Carr, Rotonya M, Kaplan, David E, Haas, Mary E, MacLean, Matthew T, Witschey, Walter R, Zhu, Xiang, Tcheandjieu, Catherine, Kember, Rachel L, Kranzler, Henry R, Verma, Anurag, Giri, Ayush, Klarin, Derek M, Sun, Yan V, Huang, Jie, Huffman, Jennifer E, Creasy, Kate Townsend, Hand, Nicholas J, Liu, Ching-Ti, Long, Michelle T, Yao, Jie, Budoff, Matthew, Tan, Jingyi, Li, Xiaohui, Lin, Henry J, Chen, Yii-Der Ida, Taylor, Kent D, Chang, Ruey-Kang, Krauss, Ronald M, Vilarinho, Silvia, Brancale, Joseph, Nielsen, Jonas B, Locke, Adam E, Jones, Marcus B, Verweij, Niek, Baras, Aris, Reddy, K Rajender, Neuschwander-Tetri, Brent A, Schwimmer, Jeffrey B, Sanyal, Arun J, Chalasani, Naga, Ryan, Kathleen A, Mitchell, Braxton D, Gill, Dipender, Wells, Andrew D, Manduchi, Elisabetta, Saiman, Yedidya, Mahmud, Nadim, Miller, Donald R, Reaven, Peter D, Phillips, Lawrence S, Muralidhar, Sumitra, DuVall, Scott L, Lee, Jennifer S, Assimes, Themistocles L, Pyarajan, Saiju, Cho, Kelly, Edwards, Todd L, Damrauer, Scott M, Wilson, Peter W, Gaziano, J Michael, O’Donnell, Christopher J, Khera, Amit V, Grant, Struan FA, Brown, Christopher D, Tsao, Philip S, Saleheen, Danish, Lotta, Luca A, Bastarache, Lisa, Anstee, Quentin M, Daly, Ann K, Meigs, James B, Rotter, Jerome I, Lynch, Julie A, Rader, Daniel J, Voight, Benjamin F, and Chang, Kyong-Mi

Subjects
Genetics, Liver Disease, Human Genome, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Aetiology, 2.1 Biological and endogenous factors, Alanine Transaminase, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Lipase, Membrane Proteins, Non-alcoholic Fatty Liver Disease, Polymorphism, Single Nucleotide, Protein Serine-Threonine Kinases, Regeneron Genetics Center, Geisinger-Regeneron DiscovEHR Collaboration, EPoS Consortium, VA Million Veteran Program, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P

Published
2022

25. Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration

Author

Austin-Zimmerman, Isabelle, Levey, Daniel F., Giannakopoulou, Olga, Deak, Joseph D., Galimberti, Marco, Adhikari, Keyrun, Zhou, Hang, Denaxas, Spiros, Irizar, Haritz, Kuchenbaecker, Karoline, McQuillin, Andrew, Concato, John, Buysse, Daniel J., Gaziano, J. Michael, Gottlieb, Daniel J., Polimanti, Renato, Stein, Murray B., Bramon, Elvira, and Gelernter, Joel

Published
2023
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26. A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium

Author

Midttun, Øivind, Ulvik, Arve, Meyer, Klaus, Zahed, Hana, Giles, Graham G., Manjer, Jonas, Sandsveden, Malte, Langhammer, Arnulf, Sørgjerd, Elin Pettersen, Behndig, Annelie F., Johansson, Mikael, Freedman, Neal D., Huang, Wen-Yi, Chen, Chu, Prentice, Ross, Stevens, Victoria L., Wang, Ying, Le Marchand, Loïc, Weinstein, Stephanie J., Cai, Qiuyin, Arslan, Alan A., Chen, Yu, Shu, Xiao-Ou, Zheng, Wei, Yuan, Jian-Min, Koh, Woon-Puay, Visvanathan, Kala, Sesso, Howard D., Zhang, Xuehong, Gaziano, J. Michael, Fanidi, Anouar, Robbins, Hilary A., Brennan, Paul, Johansson, Mattias, and Ueland, Per M.

Published
2023
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27. Genetically regulated multi-omics study for symptom clusters of posttraumatic stress disorder highlights pleiotropy with hematologic and cardio-metabolic traits

Author

Pathak, Gita A, Singh, Kritika, Wendt, Frank R, Fleming, Tyne W, Overstreet, Cassie, Koller, Dora, Tylee, Daniel S, De Angelis, Flavio, Cabrera Mendoza, Brenda, Levey, Daniel F, Koenen, Karestan C, Krystal, John H, Pietrzak, Robert H, O’ Donell, Christopher, Gaziano, J Michael, Falcone, Guido, Stein, Murray B, Gelernter, Joel, Pasaniuc, Bogdan, Mancuso, Nicholas, Davis, Lea K, and Polimanti, Renato

Subjects
Biotechnology, Human Genome, Mental Health, Post-Traumatic Stress Disorder (PTSD), Brain Disorders, Anxiety Disorders, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Mental health, Metabolic and endocrine, Good Health and Well Being, Diagnostic and Statistical Manual of Mental Disorders, Humans, Phenotype, Stress Disorders, Post-Traumatic, Syndrome, Veterans, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may arise in response to severe traumatic event and is diagnosed based on three main symptom clusters (reexperiencing, avoidance, and hyperarousal) per the Diagnostic Manual of Mental Disorders (version DSM-IV-TR). In this study, we characterized the biological heterogeneity of PTSD symptom clusters by performing a multi-omics investigation integrating genetically regulated gene, splicing, and protein expression in dorsolateral prefrontal cortex tissue within a sample of US veterans enrolled in the Million Veteran Program (N total = 186,689). We identified 30 genes in 19 regions across the three PTSD symptom clusters. We found nine genes to have cell-type specific expression, and over-representation of miRNA-families - miR-148, 30, and 8. Gene-drug target prioritization approach highlighted cyclooxygenase and acetylcholine compounds. Next, we tested molecular-profile based phenome-wide impact of identified genes with respect to 1678 phenotypes derived from the Electronic Health Records of the Vanderbilt University biorepository (N = 70,439). Lastly, we tested for local genetic correlation across PTSD symptom clusters which highlighted metabolic (e.g., obesity, diabetes, vascular health) and laboratory traits (e.g., neutrophil, eosinophil, tau protein, creatinine kinase). Overall, this study finds comprehensive genomic evidence including clinical and regulatory profiles between PTSD, hematologic and cardiometabolic traits, that support comorbidities observed in epidemiologic studies of PTSD.

Published
2022

31. African ancestry GWAS of dementia in a large military cohort identifies significant risk loci

Author

Sherva, Richard, Zhang, Rui, Sahelijo, Nathan, Jun, Gyungah, Anglin, Tori, Chanfreau, Catherine, Cho, Kelly, Fonda, Jennifer R., Gaziano, J. Michael, Harrington, Kelly M., Ho, Yuk-Lam, Kremen, William S., Litkowski, Elizabeth, Lynch, Julie, Neale, Zoe, Roussos, Panos, Marra, David, Mez, Jesse, Miller, Mark W., Salat, David H., Tsuang, Debby, Wolf, Erika, Zeng, Qing, Panizzon, Matthew S., Merritt, Victoria C., Farrer, Lindsay A., Hauger, Richard L., and Logue, Mark W.

Published
2023
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33. Genetic Inhibition of APOL1 Pore-Forming Function Prevents APOL1-Mediated Kidney Disease

Author

Hung, Adriana M., Assimon, Victoria A., Chen, Hua-Chang, Yu, Zhihong, Vlasschaert, Caitlyn, Triozzi, Jefferson L., Chan, Helen, Wheless, Lee, Wilson, Otis, Shah, Shailja C., Mack, Taralynn, Thompson, Trevor, Matheny, Michael E., Chandrasekar, Saranya, Mozaffari, Sahar V., Chung, Cecilia P., Tsao, Philip, Susztak, Katalin, Siew, Edward D., Estrada, Karol, Gaziano, J. Michael, Graham, Robert R., Tao, Ran, Hoek, Maarten, Robinson-Cohen, Cassianne, Green, Eric M., Bick, Alexander G., Muralidhar, Sumitra, Moser, Jennifer, Deen, Jennifer E., Tsao, Philip S., Gaziano, J. Michael, Hauser, Elizabeth, Kilbourne, Amy, Luoh, Shiuh-Wen, Matheny, Michael, Oslin, Dave, Churby, Lori, Whitbourne, Stacey B., Brewer, Jessica V., Shayan, Shahpoor (Alex), Selva, Luis E., Pyarajan, Saiju, Cho, Kelly, DuVall, Scott L., Brophy, Mary T., Stephens, Brady, Connor, Todd, Argyres, Dean P., Assimes, Tim, Hung, Adriana, Kranzler, Henry, Aguayo, Samuel, Ahuja, Sunil, Alexander, Kathrina, Androulakis, Xiao M., Balasubramanian, Prakash, Ballas, Zuhair, Beckham, Jean, Bhushan, Sujata, Boyko, Edward, Cohen, David, Dellitalia, Louis, Faulk, L. Christine, Fayad, Joseph, Fujii, Daryl, Gappy, Saib, Gesek, Frank, Greco, Jennifer, Godschalk, Michael, Gress, Todd W., Gupta, Samir, Gutierrez, Salvador, Harley, John, Hammer, Kimberly, Hamner, Mark, Hurley, Robin, Iruvanti, Pran, Jacono, Frank, Jhala, Darshana, Kinlay, Scott, Klein, Jon, Landry, Michael, Liang, Peter, Liangpunsakul, Suthat, Lichy, Jack, Mahan, C. Scott, Marrache, Ronnie, Mastorides, Stephen, Mates, Elisabeth, Mattocks, Kristin, Meyer, Paul, Moorman, Jonathan, Morgan, Timothy, Murdoch, Maureen, Norton, James, Okusaga, Olaoluwa, Oursler, Kris Ann, Palacio, Ana, Poon, Samuel, Potter, Emily, Rauchman, Michael, Servatius, Richard, Sharma, Satish, Smith, River, Sriram, Peruvemba, Strollo, Patrick, Jr., Tandon, Neeraj, Tsao, Philip, Villareal, Gerardo, Wallbom, Agnes, Walsh, Jessica, Wells, John, Whittle, Jeffrey, Whooley, Mary, Williams, Allison E., Wilson, Peter, Xu, Junzhe, and Yeh, Shing Shing

Published
2023
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36. Endogenous sex steroid hormones and risk of liver cancer among US men: Results from the Liver Cancer Pooling Project

Author

Wu, Zeni, Petrick, Jessica L., Florio, Andrea A., Guillemette, Chantal, Beane Freeman, Laura E., Buring, Julie E., Bradwin, Gary, Caron, Patrick, Chen, Yu, Eliassen, A. Heather, Engel, Lawrence S., Freedman, Neal D., Gaziano, J. Michael, Giovannuci, Edward L., Hofmann, Jonathan N., Huang, Wen-Yi, Kirsh, Victoria A., Kitahara, Cari M., Koshiol, Jill, Lee, I-Min, Liao, Linda M., Newton, Christina C., Palmer, Julie R., Purdue, Mark P., Rohan, Thomas E., Rosenberg, Lynn, Sesso, Howard D., Sinha, Rashmi, Stampfer, Meir J., Um, Caroline Y., Van Den Eeden, Stephen K., Visvanathan, Kala, Wactawski-Wende, Jean, Zeleniuch-Jacquotte, Anne, Zhang, Xuehong, Graubard, Barry I., Campbell, Peter T., and McGlynn, Katherine A.

Published
2023
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37. Exogenous hormone use, reproductive factors and risk of intrahepatic cholangiocarcinoma among women: results from cohort studies in the Liver Cancer Pooling Project and the UK Biobank

Author

Petrick, Jessica L, McMenamin, Úna C, Zhang, Xuehong, Zeleniuch-Jacquotte, Anne, Wactawski-Wende, Jean, Simon, Tracey G, Sinha, Rashmi, Sesso, Howard D, Schairer, Catherine, Rosenberg, Lynn, Rohan, Thomas E, Robien, Kim, Purdue, Mark P, Poynter, Jenny N, Palmer, Julie R, Lu, Yunxia, Linet, Martha S, Liao, Linda M, Lee, I-Min, Koshiol, Jill, Kitahara, Cari M, Kirsh, Victoria A, Hofmann, Jonathan N, Graubard, Barry I, Giovannucci, Edward, Gaziano, J Michael, Gapstur, Susan M, Freedman, Neal D, Florio, Andrea A, Chong, Dawn Q, Chen, Yu, Chan, Andrew T, Buring, Julie E, Freeman, Laura E Beane, Bea, Jennifer W, Cardwell, Christopher R, Campbell, Peter T, and McGlynn, Katherine A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Liver Disease, Cancer, Digestive Diseases, Contraception/Reproduction, Clinical Research, Digestive Diseases - (Gallbladder), Liver Cancer, Prevention, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Good Health and Well Being, Aged, Bile Ducts, Bile Ducts, Intrahepatic, Biological Specimen Banks, Cholangiocarcinoma, Cohort Studies, Contraceptives, Oral, Hormonal, Estrogen Receptor alpha, Estrogen Receptor beta, Female, Gene Expression Regulation, Neoplastic, Hormones, Humans, Hysterectomy, Liver Neoplasms, Menopause, Middle Aged, Proportional Hazards Models, Risk Factors, United Kingdom, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundIntrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and -β, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated with increased ICC risk, further supporting a hormonal aetiology. However, no observational studies have examined the associations between exogenous hormone use and reproductive factors, as proxies of endogenous hormone levels, and risk of ICC.MethodsWe harmonised data from 1,107,498 women who enroled in 12 North American-based cohort studies (in the Liver Cancer Pooling Project, LCPP) and the UK Biobank between 1980-1998 and 2006-2010, respectively. Cox proportional hazards regression models were used to generate hazard ratios (HR) and 95% confidence internals (CI). Then, meta-analytic techniques were used to combine the estimates from the LCPP (n = 180 cases) and the UK Biobank (n = 57 cases).ResultsHysterectomy was associated with a doubling of ICC risk (HR = 1.98, 95% CI: 1.27-3.09), compared to women aged 50-54 at natural menopause. Long-term oral contraceptive use (9+ years) was associated with a 62% increased ICC risk (HR = 1.62, 95% CI: 1.03-2.55). There was no association between ICC risk and other exogenous hormone use or reproductive factors.ConclusionsThis study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.

Published
2020

39. Genome-Wide Association Study of CKD Progression

Author

Robinson-Cohen, Cassianne, Triozzi, Jefferson L., Rowan, Bryce, He, Jing, Chen, Hua C., Zheng, Neil S., Wei, Wei-Qi, Wilson, Otis D., Hellwege, Jacklyn N., Tsao, Philip S., Gaziano, J. Michael, Bick, Alexander, Matheny, Michael E., Chung, Cecilia P., Lipworth, Loren, Siew, Edward D., Ikizler, T. Alp, Tao, Ran, and Hung, Adriana M.

Published
2023
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42. Healthy lifestyle and prostate cancer risk in the Million Veteran Program

Author

Pagadala, Meghana S., primary, Lui, Asona, additional, Lynch, Julie, additional, Karunamuni, Roshan, additional, Lee, Kyung Min, additional, Plym, Anna, additional, Rose, Brent S., additional, Carter, Hannah, additional, Kibel, Adam S., additional, DuVall, Scott L., additional, Vassy, Jason, additional, Gaziano, J. Michael, additional, Panizzon, Matthew S., additional, Hauger, Richard L., additional, and Seibert, Tyler M., additional

Published
2024
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43. Remote delivery of cancer genetic testing in veterans with metastatic prostate cancer: A Million Veteran Program study.

Author

Montgomery, Robert Bruce, primary, Lynch, Julie Ann, additional, Brown, Jessica, additional, Maxwell, Kara Noelle, additional, Kabilovic, Nismeta, additional, Stoll, Katie, additional, Simon, Julie, additional, Kogan, Maria, additional, Whitbourne, Stacey B., additional, Muralidhar, Sumitra, additional, Ramoni, Rachel, additional, Gaziano, J. Michael, additional, Cheng, Heather H., additional, Etzioni, Ruth Douglas, additional, and Pritchard, Colin C., additional

Published
2024
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44. Potentially inappropriate medications and their association with frailty, unplanned hospitalizations, and mortality in patients with cancer treated in the national U.S. Veterans Affairs Healthcare System.

Author

La, Jennifer, primary, Hshieh, Tammy, additional, Hamparsumian, Anahid, additional, Zwolinski, Robert, additional, Wood, Jameson, additional, Dharne, Mayuri, additional, Gaziano, J. Michael, additional, Brophy, Mary T., additional, Do, Nhan, additional, Munshi, Nikhil C., additional, Driver, Jane A., additional, Abel, Gregory A., additional, Fillmore, Nathanael, additional, and DuMontier, Clark, additional

Published
2024
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45. Large-scale genome-wide association study of coronary artery disease in genetically diverse populations

Author

Tcheandjieu, Catherine, Zhu, Xiang, Hilliard, Austin T., Clarke, Shoa L., Napolioni, Valerio, Ma, Shining, Lee, Kyung Min, Fang, Huaying, Chen, Fei, Lu, Yingchang, Tsao, Noah L., Raghavan, Sridharan, Koyama, Satoshi, Gorman, Bryan R., Vujkovic, Marijana, Klarin, Derek, Levin, Michael G., Sinnott-Armstrong, Nasa, Wojcik, Genevieve L., Plomondon, Mary E., Maddox, Thomas M., Waldo, Stephen W., Bick, Alexander G., Pyarajan, Saiju, Huang, Jie, Song, Rebecca, Ho, Yuk-Lam, Buyske, Steven, Kooperberg, Charles, Haessler, Jeffrey, Loos, Ruth J. F., Do, Ron, Verbanck, Marie, Chaudhary, Kumardeep, North, Kari E., Avery, Christy L., Graff, Mariaelisa, Haiman, Christopher A., Le Marchand, Loïc, Wilkens, Lynne R., Bis, Joshua C., Leonard, Hampton, Shen, Botong, Lange, Leslie A., Giri, Ayush, Dikilitas, Ozan, Kullo, Iftikhar J., Stanaway, Ian B., Jarvik, Gail P., Gordon, Adam S., Hebbring, Scott, Namjou, Bahram, Kaufman, Kenneth M., Ito, Kaoru, Ishigaki, Kazuyoshi, Kamatani, Yoichiro, Verma, Shefali S., Ritchie, Marylyn D., Kember, Rachel L., Baras, Aris, Lotta, Luca A., Kathiresan, Sekar, Hauser, Elizabeth R., Miller, Donald R., Lee, Jennifer S., Saleheen, Danish, Reaven, Peter D., Cho, Kelly, Gaziano, J. Michael, Natarajan, Pradeep, Huffman, Jennifer E., Voight, Benjamin F., Rader, Daniel J., Chang, Kyong-Mi, Lynch, Julie A., Damrauer, Scott M., Wilson, Peter W. F., Tang, Hua, Sun, Yan V., Tsao, Philip S., O’Donnell, Christopher J., and Assimes, Themistocles L.

Published
2022
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47. Rare Genetic Variants Associated With Sudden Cardiac Death in Adults

Author

Khera, Amit V, Mason-Suares, Heather, Brockman, Deanna, Wang, Minxian, VanDenburgh, Martin J, Senol-Cosar, Ozlem, Patterson, Candace, Newton-Cheh, Christopher, Zekavat, Seyedeh M, Pester, Julie, Chasman, Daniel I, Kabrhel, Christopher, Jensen, Majken K, Manson, JoAnn E, Gaziano, J Michael, Taylor, Kent D, Sotoodehnia, Nona, Post, Wendy S, Rich, Stephen S, Rotter, Jerome I, Lander, Eric S, Rehm, Heidi L, Ng, Kenney, Philippakis, Anthony, Lebo, Matthew, Albert, Christine M, and Kathiresan, Sekar

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Genetics, Clinical Research, Heart Disease, Cardiovascular, 4.2 Evaluation of markers and technologies, Aetiology, Detection, screening and diagnosis, 2.4 Surveillance and distribution, 2.1 Biological and endogenous factors, Good Health and Well Being, Aged, Aged, 80 and over, Case-Control Studies, Death, Sudden, Cardiac, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Exome Sequencing, gene sequencing, genomic medicine, sudden cardiac death, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundSudden cardiac death occurs in ∼220,000 U.S. adults annually, the majority of whom have no prior symptoms or cardiovascular diagnosis. Rare pathogenic DNA variants in any of 49 genes can pre-dispose to 4 important causes of sudden cardiac death: cardiomyopathy, coronary artery disease, inherited arrhythmia syndrome, and aortopathy or aortic dissection.ObjectivesThis study assessed the prevalence of rare pathogenic variants in sudden cardiac death cases versus controls, and the prevalence and clinical importance of such mutations in an asymptomatic adult population.MethodsThe authors performed whole-exome sequencing in a case-control cohort of 600 adult-onset sudden cardiac death cases and 600 matched controls from 106,098 participants of 6 prospective cohort studies. Observed DNA sequence variants in any of 49 genes with known association to cardiovascular disease were classified as pathogenic or likely pathogenic by a clinical laboratory geneticist blinded to case status. In an independent population of 4,525 asymptomatic adult participants of a prospective cohort study, the authors performed whole-genome sequencing and determined the prevalence of pathogenic or likely pathogenic variants and prospective association with cardiovascular death.ResultsAmong the 1,200 sudden cardiac death cases and controls, the authors identified 5,178 genetic variants and classified 14 as pathogenic or likely pathogenic. These 14 variants were present in 15 individuals, all of whom had experienced sudden cardiac death-corresponding to a pathogenic variant prevalence of 2.5% in cases and 0% in controls (p

Published
2019

48. Harmonizing Genetic Ancestry and Self-identified Race/Ethnicity in Genome-wide Association Studies

Author

Fang, Huaying, Hui, Qin, Lynch, Julie, Honerlaw, Jacqueline, Assimes, Themistocles L, Huang, Jie, Vujkovic, Marijana, Damrauer, Scott M, Pyarajan, Saiju, Gaziano, J Michael, DuVall, Scott L, O’Donnell, Christopher J, Cho, Kelly, Chang, Kyong-Mi, Wilson, Peter WF, Tsao, Philip S, Sun, Yan, Tang, Hua, Ramoni, Rachel, Breeling, Jim, Huang, Grant, Muralidhar, Sumitra, Moser, Jennifer, Whitbourne, Stacey B, Brewer, Jessica V, Concato, John, Warren, Stuart, Argyres, Dean P, Stephens, Brady, Brophy, Mary T, Humphries, Donald E, Do, Nhan, Shayan, Shahpoor, Nguyen, Xuan-Mai T, Hauser, Elizabeth, Sun, Yan V, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Harley, John, Whittle, Jeffrey, Beckham, Jean, Wells, John, Gutierrez, Salvador, Gibson, Gretchen, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Haddock, Kathlyn Sue, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Buford, Malcolm, Mastorides, Stephen, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Swann, Alan, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Washburn, Ronald, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Callaghan, John, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Gutierrez, Amparo, Schifman, Ronald, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Oehlert, Mary, Wallbom, Agnes, Fernando, Ronald, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Anderson, Gwenevere, Sonel, Elif, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Fayad, Joseph, Hung, Adriana, and Lichy, Jack

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Generic health relevance, Algorithms, Ethnicity, Genome-Wide Association Study, Humans, Machine Learning, Racial Groups, Support Vector Machine, VA Million Veteran Program, biobank, ethnicity-specific trait loci, genetic ancestry, multi-ethnic cohort, self-reported race/ethnicity, stratified analysis, trans-ethnic GWAS, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Large-scale multi-ethnic cohorts offer unprecedented opportunities to elucidate the genetic factors influencing complex traits related to health and disease among minority populations. At the same time, the genetic diversity in these cohorts presents new challenges for analysis and interpretation. We consider the utility of race and/or ethnicity categories in genome-wide association studies (GWASs) of multi-ethnic cohorts. We demonstrate that race/ethnicity information enhances the ability to understand population-specific genetic architecture. To address the practical issue that self-identified racial/ethnic information may be incomplete, we propose a machine learning algorithm that produces a surrogate variable, termed HARE. We use height as a model trait to demonstrate the utility of HARE and ethnicity-specific GWASs.

Published
2019

49. Genome-wide Association Study of Maximum Habitual Alcohol Intake in >140,000 U.S. European and African American Veterans Yields Novel Risk Loci

Author

Gelernter, Joel, Sun, Ning, Polimanti, Renato, Pietrzak, Robert H, Levey, Daniel F, Lu, Qiongshi, Hu, Yiming, Li, Boyang, Radhakrishnan, Krishnan, Aslan, Mihaela, Cheung, Kei-Hoi, Li, Yuli, Rajeevan, Nallakkandi, Sayward, Fred, Harrington, Kelly, Chen, Quan, Cho, Kelly, Honerlaw, Jacqueline, Pyarajan, Saiju, Lencz, Todd, Quaden, Rachel, Shi, Yunling, Hunter-Zinck, Haley, Gaziano, J Michael, Kranzler, Henry R, Concato, John, Zhao, Hongyu, Stein, Murray B, Program, Department of Veterans Affairs Cooperative Studies, and Program, Million Veteran

Subjects
Brain Disorders, Genetics, Human Genome, Substance Misuse, Alcoholism, Alcohol Use and Health, Prevention, Good Health and Well Being, Adolescent, Adult, Black or African American, Aged, Aged, 80 and over, Alcohol Drinking, Alcoholism, Female, Genome-Wide Association Study, Humans, Linear Models, Male, Middle Aged, Receptors, Corticotropin-Releasing Hormone, United States, Veterans, White People, Young Adult, ADH1B, CRHR1, Genome-wide association study, Habitual alcohol use, Million Veteran Program, Department of Veterans Affairs Cooperative Studies Program, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundHabitual alcohol use can be an indicator of alcohol dependence, which is associated with a wide range of serious health problems.MethodsWe completed a genome-wide association study in 126,936 European American and 17,029 African American subjects in the Veterans Affairs Million Veteran Program for a quantitative phenotype based on maximum habitual alcohol consumption.ResultsADH1B, on chromosome 4, was the lead locus for both populations: for the European American sample, rs1229984 (p = 4.9 × 10-47); for African American, rs2066702 (p = 2.3 × 10-12). In the European American sample, we identified three additional genome-wide-significant maximum habitual alcohol consumption loci: on chromosome 17, rs77804065 (p = 1.5 × 10-12), at CRHR1 (corticotropin-releasing hormone receptor 1); the protein product of this gene is involved in stress and immune responses; and on chromosomes 8 and 10. European American and African American samples were then meta-analyzed; the associated region at CRHR1 increased in significance to 1.02 × 10-13, and we identified two additional genome-wide significant loci, FGF14 (p = 9.86 × 10-9) (chromosome 13) and a locus on chromosome 11. Besides ADH1B, none of the five loci have prior genome-wide significant support. Post-genome-wide association study analysis identified genetic correlation to other alcohol-related traits, smoking-related traits, and many others. Replications were observed in UK Biobank data. Genetic correlation between maximum habitual alcohol consumption and alcohol dependence was 0.87 (p = 4.78 × 10-9). Enrichment for cell types included dopaminergic and gamma-aminobutyric acidergic neurons in midbrain, and pancreatic delta cells.ConclusionsThe present study supports five novel alcohol-use risk loci, with particularly strong statistical support for CRHR1. Additionally, we provide novel insight regarding the biology of harmful alcohol use.

Published
2019

50. Gender Differences in Demographic and Health Characteristics of the Million Veteran Program Cohort

Author

Harrington, Kelly M, Nguyen, Xuan-Mai T, Song, Rebecca J, Hannagan, Keri, Quaden, Rachel, Gagnon, David R, Cho, Kelly, Deen, Jennifer E, Muralidhar, Sumitra, O’Leary, Timothy J, Gaziano, John Michael, Whitbourne, Stacey B, Gaziano, J Michael, Ramoni, Rachel, Breeling, Jim, Chang, Kyong-Mi, Huang, Grant, O’Donnell, Christopher J, Tsao, Philip S, Moser, Jennifer, Brewer, Jessica V, Concato, John, Warren, Stuart, Pharm, D, Argyres, Dean P, Tsao, Philip, Stephens, Brady, Brophy, Mary T, Humphries, Donald E, Do, Nhan, Shayan, Shahpoor, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Harley, John, Whittle, Jeffrey, Beckham, Jean, Wells, John, Gutierrez, Salvador, Gibson, Gretchen, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Haddock, Kathlyn Sue, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Buford, Malcolm, Mastorides, Stephen, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Swann, Alan, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Washburn, Ronald, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Callaghan, John, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Gutierrez, Amparo, Schifman, Ronald, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Oehlert, Mary, Wallbom, Agnes, Fernando, Ronald, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Anderson, Gwenevere, Sonel, Elif, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Fayad, Joseph, and Hung, Adriana

Subjects
Health Services and Systems, Health Sciences, Cardiovascular, Clinical Research, Prevention, 2.4 Surveillance and distribution, Aetiology, Good Health and Well Being, Adult, Aged, Cardiovascular Diseases, Cohort Studies, Female, Health Status, Humans, Male, Mental Disorders, Middle Aged, Migraine Disorders, Musculoskeletal Diseases, Physical Fitness, Prevalence, Sex Distribution, Sex Factors, Smoking, Surveys and Questionnaires, United States, United States Department of Veterans Affairs, Veterans, Veterans Health, Young Adult, VA Million Veteran Program, Paediatrics and Reproductive Medicine, Public Health and Health Services, Public Health, Midwifery, Public health, Policy and administration
Abstract

BackgroundThe Department of Veterans Affairs Million Veteran Program (MVP) is the largest ongoing cohort program of its kind, with 654,903 enrollees as of June 2018. The objectives of this study were to examine gender differences in the MVP cohort with respect to response and enrollment rates; demographic, health, and health care characteristics; and prevalence of self-reported health conditions.MethodsThe MVP Baseline Survey was completed by 415,694 veterans (8% women), providing self-report measures of demographic characteristics, health status, and medical history.ResultsRelative to men, women demonstrated a higher positive responder rate (23.0% vs. 16.0%), slightly higher enrollment rate (13.5% vs. 12.9%), and, among enrollees, a lower survey completion rate (59.7% vs. 63.8%). Women were younger, more racially diverse, had higher educational attainment, and were less likely to be married or cohabitating with a partner than men. Women were more likely to report good to excellent health status but poorer physical fitness, and less likely to report lifetime smoking and drinking than men. Compared with men, women veterans showed an increased prevalence of musculoskeletal conditions, thyroid problems, gastrointestinal conditions, migraine headaches, and mental health disorders, as well as a decreased prevalence of gout, cardiovascular diseases, high cholesterol, diabetes, and hearing problems.ConclusionsThese results revealed some substantial gender differences in the research participation rates, demographic profile, health characteristics, and prevalence of health conditions for veterans in the MVP cohort. Findings highlight the need for tailoring recruitment efforts to ensure representation of the increasing women veteran population receiving care through the Veterans Health Administration.

Published
2019

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