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8 results on '"Program, VA Million Veteran"'

1. Genetic and clinical determinants of abdominal aortic diameter: genome-wide association studies, exome array data and Mendelian randomization study

Author

Portilla-Fernandez, Eliana, Klarin, Derek, Hwang, Shih-Jen, Biggs, Mary L, Bis, Joshua C, Weiss, Stefan, Rospleszcz, Susanne, Natarajan, Pradeep, Hoffmann, Udo, Rogers, Ian S, Truong, Quynh A, Völker, Uwe, Dörr, Marcus, Bülow, Robin, Criqui, Michael H, Allison, Matthew, Ganesh, Santhi K, Yao, Jie, Waldenberger, Melanie, Bamberg, Fabian, Rice, Kenneth M, Essers, Jeroen, Kapteijn, Daniek MC, van der Laan, Sander W, de Knegt, Rob J, Ghanbari, Mohsen, Felix, Janine F, Ikram, M Arfan, Kavousi, Maryam, Uitterlinden, Andre G, Roks, Anton JM, Danser, AH Jan, Tsao, Philip S, Damrauer, Scott M, Guo, Xiuqing, Rotter, Jerome I, Psaty, Bruce M, Kathiresan, Sekar, Völzke, Henry, Peters, Annette, Johnson, Craig, Strauch, Konstantin, Meitinger, Thomas, O’Donnell, Christopher J, Dehghan, Abbas, and Program, VA Million Veteran

Subjects
Prevention, Human Genome, Cardiovascular, Genetics, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Exome, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Triglycerides, VA Million Veteran Program, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Progressive dilation of the infrarenal aortic diameter is a consequence of the ageing process and is considered the main determinant of abdominal aortic aneurysm (AAA). We aimed to investigate the genetic and clinical determinants of abdominal aortic diameter (AAD). We conducted a meta-analysis of genome-wide association studies in 10 cohorts (n = 13 542) imputed to the 1000 Genome Project reference panel including 12 815 subjects in the discovery phase and 727 subjects [Partners Biobank cohort 1 (PBIO)] as replication. Maximum anterior-posterior diameter of the infrarenal aorta was used as AAD. We also included exome array data (n = 14 480) from seven epidemiologic studies. Single-variant and gene-based associations were done using SeqMeta package. A Mendelian randomization analysis was applied to investigate the causal effect of a number of clinical risk factors on AAD. In genome-wide association study (GWAS) on AAD, rs74448815 in the intronic region of LDLRAD4 reached genome-wide significance (beta = -0.02, SE = 0.004, P-value = 2.10 × 10-8). The association replicated in the PBIO1 cohort (P-value = 8.19 × 10-4). In exome-array single-variant analysis (P-value threshold = 9 × 10-7), the lowest P-value was found for rs239259 located in SLC22A20 (beta = 0.007, P-value = 1.2 × 10-5). In the gene-based analysis (P-value threshold = 1.85 × 10-6), PCSK5 showed an association with AAD (P-value = 8.03 × 10-7). Furthermore, in Mendelian randomization analyses, we found evidence for genetic association of pulse pressure (beta = -0.003, P-value = 0.02), triglycerides (beta = -0.16, P-value = 0.008) and height (beta = 0.03, P-value

Published
2022

2. Genetic interactions drive heterogeneity in causal variant effect sizes for gene expression and complex traits

Author

Patel, Roshni A, Musharoff, Shaila A, Spence, Jeffrey P, Pimentel, Harold, Tcheandjieu, Catherine, Mostafavi, Hakhamanesh, Sinnott-Armstrong, Nasa, Clarke, Shoa L, Smith, Courtney J, Program, VA Million Veteran, Durda, Peter P, Taylor, Kent D, Tracy, Russell, Liu, Yongmei, Johnson, W Craig, Aguet, Francois, Ardlie, Kristin G, Gabriel, Stacey, Smith, Josh, Nickerson, Deborah A, Rich, Stephen S, Rotter, Jerome I, Tsao, Philip S, Assimes, Themistocles L, and Pritchard, Jonathan K

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Atherosclerosis, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Cholesterol, LDL, Gene Expression, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Polymorphism, Single Nucleotide, White People, V.A. Million Veteran Program, complex traits, genetic correlation, genome-wide association, population genetics, statistical genetics, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Despite the growing number of genome-wide association studies (GWASs), it remains unclear to what extent gene-by-gene and gene-by-environment interactions influence complex traits in humans. The magnitude of genetic interactions in complex traits has been difficult to quantify because GWASs are generally underpowered to detect individual interactions of small effect. Here, we develop a method to test for genetic interactions that aggregates information across all trait-associated loci. Specifically, we test whether SNPs in regions of European ancestry shared between European American and admixed African American individuals have the same causal effect sizes. We hypothesize that in African Americans, the presence of genetic interactions will drive the causal effect sizes of SNPs in regions of European ancestry to be more similar to those of SNPs in regions of African ancestry. We apply our method to two traits: gene expression in 296 African Americans and 482 European Americans in the Multi-Ethnic Study of Atherosclerosis (MESA) and low-density lipoprotein cholesterol (LDL-C) in 74K African Americans and 296K European Americans in the Million Veteran Program (MVP). We find significant evidence for genetic interactions in our analysis of gene expression; for LDL-C, we observe a similar point estimate, although this is not significant, most likely due to lower statistical power. These results suggest that gene-by-gene or gene-by-environment interactions modify the effect sizes of causal variants in human complex traits.

Published
2022

3. Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Author

Chen, Ming-Huei, Raffield, Laura M, Mousas, Abdou, Sakaue, Saori, Huffman, Jennifer E, Moscati, Arden, Trivedi, Bhavi, Jiang, Tao, Akbari, Parsa, Vuckovic, Dragana, Bao, Erik L, Zhong, Xue, Manansala, Regina, Laplante, Véronique, Chen, Minhui, Lo, Ken Sin, Qian, Huijun, Lareau, Caleb A, Beaudoin, Mélissa, Hunt, Karen A, Akiyama, Masato, Bartz, Traci M, Ben-Shlomo, Yoav, Beswick, Andrew, Bork-Jensen, Jette, Bottinger, Erwin P, Brody, Jennifer A, van Rooij, Frank JA, Chitrala, Kumaraswamynaidu, Cho, Kelly, Choquet, Hélène, Correa, Adolfo, Danesh, John, Di Angelantonio, Emanuele, Dimou, Niki, Ding, Jingzhong, Elliott, Paul, Esko, Tõnu, Evans, Michele K, Floyd, James S, Broer, Linda, Grarup, Niels, Guo, Michael H, Greinacher, Andreas, Haessler, Jeff, Hansen, Torben, Howson, Joanna MM, Huang, Qin Qin, Huang, Wei, Jorgenson, Eric, Kacprowski, Tim, Kähönen, Mika, Kamatani, Yoichiro, Kanai, Masahiro, Karthikeyan, Savita, Koskeridis, Fotis, Lange, Leslie A, Lehtimäki, Terho, Lerch, Markus M, Linneberg, Allan, Liu, Yongmei, Lyytikäinen, Leo-Pekka, Manichaikul, Ani, Martin, Hilary C, Matsuda, Koichi, Mohlke, Karen L, Mononen, Nina, Murakami, Yoshinori, Nadkarni, Girish N, Nauck, Matthias, Nikus, Kjell, Ouwehand, Willem H, Pankratz, Nathan, Pedersen, Oluf, Preuss, Michael, Psaty, Bruce M, Raitakari, Olli T, Roberts, David J, Rich, Stephen S, Rodriguez, Benjamin AT, Rosen, Jonathan D, Rotter, Jerome I, Schubert, Petra, Spracklen, Cassandra N, Surendran, Praveen, Tang, Hua, Tardif, Jean-Claude, Trembath, Richard C, Ghanbari, Mohsen, Völker, Uwe, Völzke, Henry, Watkins, Nicholas A, Zonderman, Alan B, Program, VA Million Veteran, Wilson, Peter WF, Li, Yun, Butterworth, Adam S, Gauchat, Jean-François, Chiang, Charleston WK, and Li, Bingshan

Subjects
Genetics, Good Health and Well Being, Asian People, Genome-Wide Association Study, HEK293 Cells, Humans, Interleukin-7, Mutation, Missense, Phenotype, Polymorphism, Single Nucleotide, White People, VA Million Veteran Program, interleukin-7, genetic architecture, fine-mapping, selective sweeps, polygenic trait score, phenome-wide association study, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10-9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.

Published
2020

4. Alcohol Consumption and Risk of Coronary Artery Disease (from the Million Veteran Program)

Author

Song, Rebecca J, Nguyen, Xuan-Mai T, Quaden, Rachel, Ho, Yuk-Lam, Justice, Amy C, Gagnon, David R, Cho, Kelly, O'Donnell, Christopher J, Concato, John, Gaziano, J Michael, Djoussé, Luc, Program, VA Million Veteran, Halasz, Ildiko, Federman, Daniel, Beckham, Jean, Sherman, Scott E, Sriram, Peruvemba, Tsao, Philip S, Boyko, Edward J, Xu, Junzhe, Lederle, Frank, Dellitalia, Louis J, McArdle, Rachel, Kaminsky, Laurence, Swann, Alan C, Hamner, Mark B, Florez, Hermes J, Pandya, Prashant, Villarreal, Gerardo, Wilson, Peter, Morgan, Timothy R, Davis, Lori, Hurley, Robin A, Meyer, Laurence, Ahuja, Sunil K, Konicki, Eric P, Cohen, David, Lichy, Jack, Whittle, Jeffrey, Haddock, Kathlyn Sue, Straub, Karl D, Callaghan, John T, Aguayo, Samuel M, Gupta, Samir, Washburn, Ronald G, Oehlert, Mary E, Hung, Adriana M, Wallbom, Agnes, Keith, Robert, Sonel, Elif, Schifman, Ronald B, Childress, Richard D, Godschalk, Michael F, Shuldiner, Alan R, Rastogi, Padmashri, Gutierrez, Salvador, Fernando, Ronald, Iruvanti, Pran R, Jhala, Darshana, Rosado-Rodriguez, Carlos, Mastorides, Stephen M, Harley, John B, Mattocks, Kristin, Robey, Brooks, Striker, Robert T, Rauchman, Michael, Wells, John, Ballas, Zuhair K, Woods, Susan S, Yeh, Shing Shing, Ratcliffe, Nora R, Klein, Jon B, Golden, Adam G, Ginzburg, Harold M, Sharma, Satish, Oursler, Kris Ann K, Whooley, Mary A, Gibson, Gretchen, and Heinz

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Substance Misuse, Brain Disorders, Heart Disease - Coronary Heart Disease, Alcoholism, Alcohol Use and Health, Heart Disease, Cardiovascular, Clinical Research, Atherosclerosis, Stroke, Oral and gastrointestinal, Good Health and Well Being, Aged, Alcohol Drinking, Alcoholic Beverages, Alcoholism, Coronary Artery Disease, Female, Humans, Male, Middle Aged, Proportional Hazards Models, Protective Factors, Risk Factors, Self Report, United States, Veterans, VA Million Veteran Program, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Moderate alcohol consumption has been associated with a lower risk of coronary artery disease (CAD) in the general population but has not been well studied in US veterans. We obtained self-reported alcohol consumption from Million Veteran Program participants. Using electronic health records, CAD events were defined as 1 inpatient or 2 outpatient diagnosis codes for CAD, or 1 code for a coronary procedure. We excluded participants with prevalent CAD (n = 69,995) or incomplete alcohol information (n = 8,449). We used a Cox proportional hazards model to estimate hazard ratios and 95% confidence intervals for CAD, adjusting for age, gender, body mass index, race, smoking, education, and exercise. Among 156,728 participants, the mean age was 65.3 years (standard deviation = 12.1) and 91% were men. There were 6,153 CAD events during a mean follow-up of 2.9 years. Adjusted hazard ratios (95% confidence intervals) for CAD were 1.00 (reference), 1.02 (0.92 to 1.13), 0.83 (0.74 to 0.93), 0.77 (0.67 to 0.87), 0.71 (0.62 to 0.81), 0.62 (0.51 to 0.76), 0.58 (0.46 to 0.74), and 0.95 (0.85 to 1.06) for categories of never drinker; former drinker; current drinkers of ≤0.5 drink/day, >0.5 to 1 drink/day, >1 to 2 drinks/day, >2 to 3 drinks/day, and >3 to 4 drinks/day; and heavy drinkers (>4 drinks/day) or alcohol use disorder, respectively. For a fixed amount of ethanol, intake at ≥3 days/week was associated with lower CAD risk compared with ≤1 day/week. Beverage preference (beer, wine, or liquor) did not influence the alcohol-CAD relation. Our data show a lower risk of CAD with light-to-moderate alcohol consumption among US veterans, and drinking frequency may provide a further reduction in risk.

Published
2018

6. Publisher Correction : Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, He, Yunye, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Georgakis, Marios K, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Caro, Ilana, Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Krebs, Kristi, Wilson, Peter W F, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Consortium, COMPASS, Consortium, INVENT, Initiative, Dutch Parelsnoer, Biobank, Estonian, Consortium, PRECISE4Q, Consortium, FinnGen, Liaw, Yi-Ching, Network, NINDS Stroke Genetics, Consortium, MEGASTROKE, Consortium, SIREN, Group, China Kadoorie Biobank Collaborative, Program, VA Million Veteran, Consortium, International Stroke Genetics, Japan, Biobank, Consortium, CHARGE, Consortium, GIGASTROKE, Millwood, Iona Y, Vaura, Felix C, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M M, Lin, Kuang, Irvin, Marguerite R, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Winsvold, Bendik Slagsvold, Kõrv, Janika, França, Paulo H C, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas G., Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Srinivasasainagendra, Vinodh, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Anderson, Christopher D, Zwart, John-Anker, Niiranen, Teemu J, Parodi, Livia, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Hachiya, Tsuyoshi, Bae, Hee-Joon, Dichgans, Martin, Debette, Stephanie, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Jürgenson, Tuuli, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Namba, Shinichi, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Posner, Daniel C, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Kamanu, Frederick K, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Koido, Masaru, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Le Grand, Quentin, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Shi, Mingyang, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Børge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Bis, Joshua C, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michèle M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-François, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke J H, Kappelle, L Jaap, Esko, Tõnu, Metspalu, Andres, Mägi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jiménez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie L M, Rannikmäe, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent N S, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engström, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibañez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muiño, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul I W, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-François, Delavaran, Hossein, Dörr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Müller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Ásgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles D A, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tárraga, Carolina, Völzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Le Grand, Quentin, Ferreira, Leslie E, Nagai, Akiko, Murakami, Yoishinori, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, van Vugt, Marion, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Völker, Uwe, de Jager, Phil L, de Cid, Rafael, Nordestgaard, Børge G, Sargurupremraj, Muralidharan, Verma, Shefali S, de Laat, Karlijn F, van Norden, Anouk G W, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul J A M, Gons, Rob A R, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank G W, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjær, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethüm, Kathrin, Gallego-Fabrega, Cristina, Lledós, Miquel, Llucià-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, José, Freijó, Marimar, Arenillas, Juan Francisco, Obach, Victor, Álvarez-Sabín, José, Molina, Carlos A, Ribó, Marc, Muñoz-Narbona, Lucia, Lopez-Cancio, Elena, Millán, Mònica, Diaz-Navarro, Rosa, Vives-Bauza, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sánchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Martí-Fàbregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet M J, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Onland-Moret, N Charlotte, and Heath, Alicia K

Subjects
Stroke, Multidisciplinary, Genetic markers, ddc:500, Predictive markers, Genome-wide association studies
Published
2022
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7. Chocolate consumption and risk of coronary artery disease: the Million Veteran Program.

Author

Ho, Yuk-Lam, Nguyen, Xuan-Mai T, Yan, Joseph Q, Vassy, Jason L, Gagnon, David R, Gaziano, J Michael, Wilson, Peter W F, Cho, Kelly, Djoussé, Luc, and Program, VA Million Veteran

Subjects
CARDIOVASCULAR diseases risk factors, NUTRITION, CACAO, INGESTION, CORONARY disease, TYPE 2 diabetes, RISK assessment, QUESTIONNAIRES, VETERANS, ELECTRONIC health records, PROPORTIONAL hazards models, SECONDARY analysis, LONGITUDINAL method
Abstract

Background Although previous studies have suggested cocoa products may promote cardiovascular health in the general population, no public data are available from patients receiving care in a national integrated health care system. Objectives We tested the hypothesis that regular chocolate consumption is associated with a lower risk of coronary artery disease (CAD) events among participants of the Million Veteran Program (MVP). Secondary analysis examined if the main hypothesis was observed among participants with type 2 diabetes. Methods We analyzed data from MVP participants who completed the food frequency section of the MVP Lifestyle Survey and were free of CAD at the time of survey completion. CAD events during follow-up (International Statistical Classification of Diseases Ninth Revision codes 410–411 and 413–414, and Tenth Revision codes I20–I25 except I25.2) were assessed using electronic health records. We fitted a Cox proportional hazard model to estimate the RR of CAD. Results Of 188,447 MVP enrollees with survey data, mean ± SD age was 64 ± 12.0 y and 90% were men. For regular chocolate (28.3 g/serving) consumption of <1 serving/mo, 1–3 servings/mo, 1 serving/wk, 2–4 servings/wk, and ≥5 servings/wk, crude incidence rates (per 1000 person-years) for fatal and nonfatal CAD events or coronary procedures were 20.2, 17.5, 16.7, 17.1, and 16.9, respectively, during a mean follow-up of 3.2 y. After adjusting for age, sex, race, and lifestyle factors, the corresponding HRs (95% CIs) were 1.00 (ref), 0.92 (0.87, 0.96), 0.88 (0.83, 0.93), 0.89 (0.84, 0.95), and 0.89 (0.84, 0.96), respectively (P for linear trend < 0.0001). In a secondary analysis of 47,265 diabetics, we did not observe a decreasing trend in CAD mortality among those who consumed ≥1 serving of chocolate a month compared with those who consumed <1 serving/mo. Conclusions Regular chocolate consumption was associated with a lower risk of CAD among veterans, but was not associated with cardiovascular disease risk in veterans with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Published
2021
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8. A saturated map of common genetic variants associated with human height

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Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U, Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D, Graham, Sarah E, Mukamel, Ronen E, Spracklen, Cassandra N, Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H, Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E, Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S, Akiyama, Masato, Allison, Matthew A, Alvarez, Marcus, Andersen, Mette K, Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F, Bollepalli, Sailalitha, Bonnycastle, Lori L, Bork-Jensen, Jette, Bradfield, Jonathan P, Bradford, Yuki, Braund, Peter S, Brody, Jennifer A, Burgdorf, Kristoffer S, Cade, Brian E, Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E Warwick, Degenhard, Frauke, Delgado, Graciela E, Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B, Engmann, Jorgen E, Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D, Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E, Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P, Goel, Anuj, Gordon, Scott D, Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F, Havulinna, Aki S, Haworth, Simon J, He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A, Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E, Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E, Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D, Isono, Masato, Jackson, Anne U, Jäger, Susanne, Jansen, Iris E, Johansson, Ingegerd, Jonas, Jost B, Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L, Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L, Kentistou, Katherine A, Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E, Knol, Maria J, Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L, Li, Shengchao A, Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian'an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, 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Wacher-Rodarte, Niels H, Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J, Watanabe, Richard M, Watkins, Hugh, Weir, David R, Werge, Thomas M, Widen, Elisabeth, Wilkens, Lynne R, Willemsen, Gonneke, Willett, Walter C, Wilson, James F, Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F, Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S, Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S, Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M, Zonderman, Alan B, Zwart, John-Anker, 23andMe Research Team, VA Million Veteran Program, DiscovEHR (DiscovEHR And MyCode Community Health Initiative), EMERGE (Electronic Medical Records And Genomics Network), Lifelines Cohort Study, PRACTICAL Consortium, Understanding Society Scientific Group, Chasman, Daniel I, Cho, Yoon Shin, Heid, Iris M, McCarthy, Mark I, Ng, Maggie CY, O'Donnell, Christopher J, Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V, Tai, E Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E, Lindgren, Cecilia M, Loos, Ruth JF, Mohlke, Karen L, North, Kari E, Stefansson, Kari, Walters, Robin G, Winkler, Thomas W, Young, Kristin L, Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L, Auton, Adam, Abecasis, Goncalo R, Willer, Cristen J, Locke, Adam E, Berndt, Sonja I, Lettre, Guillaume, Frayling, Timothy M, Okada, Yukinori, Wood, Andrew R, Visscher, Peter M, Hirschhorn, Joel N, Oral Implantology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Liability Law, Earth Sciences, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, Environmental Geography (former), Art and Culture, History, Antiquity, Sociology and Social Gerontology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Nutrition and Health, Organic Chemistry, AIMMS, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Internal Medicine, Epidemiology, Radiology & Nuclear Medicine, Clinical Genetics, Team, 23andMe Research, Program, VA Million Veteran, Initiative), DiscovEHR (DiscovEHR and 112 MyCode Community Health, Network), eMERGE (Electronic Medical Records and Genomics, Study, Lifelines Cohort, Consortium, The PRACTICAL, Group, Understanding Society Scientific, Yengo, Loïc [0000-0002-4272-9305], Apollo - University of Cambridge Repository, Laboratory Genetic Metabolic Diseases, Laboratory for General Clinical Chemistry, Geriatrics, AMS - Ageing & Vitality, APH - Aging & Later Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Heart failure & arrhythmias, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, General practice, ACS - Diabetes & metabolism, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Epidemiology and Data Science, Internal medicine, APH - Digital Health, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Hypponen, Elina, Hirschhorn, Joel N, Epigenetics of Complex Diseases and Traits, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, Joint Activities, University of Helsinki, Medicum, Complex Disease Genetics, Samuli Olli Ripatti / Principal Investigator, Helsinki Institute of Life Science HiLIFE, Department of Medicine, HUS Internal Medicine and Rehabilitation, Clinicum, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Faculty Common Matters (Faculty of Social Sciences), Research Programs Unit, HUS Abdominal Center, Tiinamaija Tuomi Research Group, CAMM - Research Program for Clinical and Molecular Metabolism, Departments of Faculty of Veterinary Medicine, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical 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Subjects
multi-ancestry, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Medizin, 45/43, Genome-wide association studies, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Linkage Disequilibrium, Gene Frequency, RARE, IMPUTATION, PRACTICAL Consortium, GWAS, genes, ARCHITECTURE, Genome, Human/genetics, Multidisciplinary, Body Height/genetics, HERITABILITY, SCORES, article, Chromosome Mapping, 631/208/721, Polymorphism, Single Nucleotide/genetics, 3142 Public health care science, environmental and occupational health, Nutritional Biology, Europe, Phenotype, Gene Frequency/genetics, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], VA Million Veteran Program, Molecular and Laser Physics, dimorphism, blood, lipid, Medical Genetics, Single Nucleotide/genetics, genetic variant, Understanding Society Scientific Group, height, genetic, Haplotypes/genetics, 631/208/205/2138, saturated map, 23andMe Research Team, Polymorphism, Single Nucleotide, single-nucleotide polymorphisms (SNPs), Europe/ethnology, Lifelines Cohort Study, RESOURCE, UK BIOBANK, REVEALS, Life Science, DiscovEHR (DiscovEHR and MyCode Community Health Initiative), Humans, Linkage Disequilibrium/genetics, genomic regions, Polymorphism, GENOME-WIDE ASSOCIATION, gene, genetic variants, human height, 631/208/480, VLAG, Medicinsk genetik, eMERGE (Electronic Medical Records and Genomics Network), Genome, Human, Spectroscopy of Cold Molecules, Quantitative traits, Genome, Human/genetics, Genome-Wide Association Study, Sample Size, Body Height, 3141 Health care science, Haplotypes, Genetic markers, 3111 Biomedicine
Abstract

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries. A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Published
2022
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