1,477 results on '"Feitosa, Mary"'
Search Results
2. Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease
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Chen, Yanhua, Du, Xiaomeng, Kuppa, Annapurna, Feitosa, Mary F, Bielak, Lawrence F, O’Connell, Jeffrey R, Musani, Solomon K, Guo, Xiuqing, Kahali, Bratati, Chen, Vincent L, Smith, Albert V, Ryan, Kathleen A, Eirksdottir, Gudny, Allison, Matthew A, Bowden, Donald W, Budoff, Matthew J, Carr, John Jeffrey, Chen, Yii-Der I, Taylor, Kent D, Oliveri, Antonino, Correa, Adolfo, Crudup, Breland F, Kardia, Sharon LR, Mosley, Thomas H, Norris, Jill M, Terry, James G, Rotter, Jerome I, Wagenknecht, Lynne E, Halligan, Brian D, Young, Kendra A, Hokanson, John E, Washko, George R, Gudnason, Vilmundur, Province, Michael A, Peyser, Patricia A, Palmer, Nicholette D, and Speliotes, Elizabeth K
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Biochemistry and Cell Biology ,Genetics ,Biological Sciences ,Digestive Diseases ,Liver Disease ,Hepatitis ,Chronic Liver Disease and Cirrhosis ,Human Genome ,Prevention ,2.1 Biological and endogenous factors ,Humans ,Non-alcoholic Fatty Liver Disease ,Genome-Wide Association Study ,Liver Cirrhosis ,Acyltransferases ,Phospholipases ,Genetic Predisposition to Disease ,Polymorphism ,Single Nucleotide ,Liver ,Protein Serine-Threonine Kinases ,Intracellular Signaling Peptides and Proteins ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Nonalcoholic fatty liver disease (NAFLD) is common and partially heritable and has no effective treatments. We carried out a genome-wide association study (GWAS) meta-analysis of imaging (n = 66,814) and diagnostic code (3,584 cases versus 621,081 controls) measured NAFLD across diverse ancestries. We identified NAFLD-associated variants at torsin family 1 member B (TOR1B), fat mass and obesity associated (FTO), cordon-bleu WH2 repeat protein like 1 (COBLL1)/growth factor receptor-bound protein 14 (GRB14), insulin receptor (INSR), sterol regulatory element-binding transcription factor 1 (SREBF1) and patatin-like phospholipase domain-containing protein 2 (PNPLA2), as well as validated NAFLD-associated variants at patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2), apolipoprotein E (APOE), glucokinase regulator (GCKR), tribbles homolog 1 (TRIB1), glycerol-3-phosphate acyltransferase (GPAM), mitochondrial amidoxime-reducing component 1 (MARC1), microsomal triglyceride transfer protein large subunit (MTTP), alcohol dehydrogenase 1B (ADH1B), transmembrane channel like 4 (TMC4)/membrane-bound O-acyltransferase domain containing 7 (MBOAT7) and receptor-type tyrosine-protein phosphatase δ (PTPRD). Implicated genes highlight mitochondrial, cholesterol and de novo lipogenesis as causally contributing to NAFLD predisposition. Phenome-wide association study (PheWAS) analyses suggest at least seven subtypes of NAFLD. Individuals in the top 10% and 1% of genetic risk have a 2.5-fold to 6-fold increased risk of NAFLD, cirrhosis and hepatocellular carcinoma. These genetic variants identify subtypes of NAFLD, improve estimates of disease risk and can guide the development of targeted therapeutics.
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- 2023
3. Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification
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Kavousi, Maryam, Bos, Maxime M, Barnes, Hanna J, Lino Cardenas, Christian L, Wong, Doris, Lu, Haojie, Hodonsky, Chani J, Landsmeer, Lennart PL, Turner, Adam W, Kho, Minjung, Hasbani, Natalie R, de Vries, Paul S, Bowden, Donald W, Chopade, Sandesh, Deelen, Joris, Benavente, Ernest Diez, Guo, Xiuqing, Hofer, Edith, Hwang, Shih-Jen, Lutz, Sharon M, Lyytikäinen, Leo-Pekka, Slenders, Lotte, Smith, Albert V, Stanislawski, Maggie A, van Setten, Jessica, Wong, Quenna, Yanek, Lisa R, Becker, Diane M, Beekman, Marian, Budoff, Matthew J, Feitosa, Mary F, Finan, Chris, Hilliard, Austin T, Kardia, Sharon LR, Kovacic, Jason C, Kral, Brian G, Langefeld, Carl D, Launer, Lenore J, Malik, Shaista, Hoesein, Firdaus AA Mohamed, Mokry, Michal, Schmidt, Reinhold, Smith, Jennifer A, Taylor, Kent D, Terry, James G, van der Grond, Jeroen, van Meurs, Joyce, Vliegenthart, Rozemarijn, Xu, Jianzhao, Young, Kendra A, Zilhão, Nuno R, Zweiker, Robert, Assimes, Themistocles L, Becker, Lewis C, Bos, Daniel, Carr, J Jeffrey, Cupples, L Adrienne, de Kleijn, Dominique PV, de Winther, Menno, den Ruijter, Hester M, Fornage, Myriam, Freedman, Barry I, Gudnason, Vilmundur, Hingorani, Aroon D, Hokanson, John E, Ikram, M Arfan, Išgum, Ivana, Jacobs, David R, Kähönen, Mika, Lange, Leslie A, Lehtimäki, Terho, Pasterkamp, Gerard, Raitakari, Olli T, Schmidt, Helena, Slagboom, P Eline, Uitterlinden, André G, Vernooij, Meike W, Bis, Joshua C, Franceschini, Nora, Psaty, Bruce M, Post, Wendy S, Rotter, Jerome I, Björkegren, Johan LM, O’Donnell, Christopher J, Bielak, Lawrence F, Peyser, Patricia A, Malhotra, Rajeev, van der Laan, Sander W, and Miller, Clint L
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Biological Sciences ,Genetics ,Heart Disease - Coronary Heart Disease ,Human Genome ,Cardiovascular ,Prevention ,Heart Disease ,Atherosclerosis ,2.1 Biological and endogenous factors ,Aetiology ,Humans ,Black People ,Coronary Artery Disease ,Genome-Wide Association Study ,Risk Factors ,European People ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci are related to bone mineralization, phosphate catabolism and hormone metabolic pathways. Several new loci harbor candidate causal genes supported by multiple lines of functional evidence and are regulators of smooth muscle cell-mediated calcification ex vivo and in vitro. Together, these findings help refine the genetic architecture of CAC and extend our understanding of the biological and potential druggable pathways underlying CAC.
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- 2023
4. X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements
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Scholz, Markus, Horn, Katrin, Pott, Janne, Wuttke, Matthias, Kühnapfel, Andreas, Nasr, M. Kamal, Kirsten, Holger, Li, Yong, Hoppmann, Anselm, Gorski, Mathias, Ghasemi, Sahar, Li, Man, Tin, Adrienne, Chai, Jin-Fang, Cocca, Massimiliano, Wang, Judy, Nutile, Teresa, Akiyama, Masato, Åsvold, Bjørn Olav, Bansal, Nisha, Biggs, Mary L., Boutin, Thibaud, Brenner, Hermann, Brumpton, Ben, Burkhardt, Ralph, Cai, Jianwen, Campbell, Archie, Campbell, Harry, Chalmers, John, Chasman, Daniel I., Chee, Miao Ling, Chee, Miao Li, Chen, Xu, Cheng, Ching-Yu, Cifkova, Renata, Daviglus, Martha, Delgado, Graciela, Dittrich, Katalin, Edwards, Todd L., Endlich, Karlhans, Michael Gaziano, J., Giri, Ayush, Giulianini, Franco, Gordon, Scott D., Gudbjartsson, Daniel F., Hallan, Stein, Hamet, Pavel, Hartman, Catharina A., Hayward, Caroline, Heid, Iris M., Hellwege, Jacklyn N., Holleczek, Bernd, Holm, Hilma, Hutri-Kähönen, Nina, Hveem, Kristian, Isermann, Berend, Jonas, Jost B., Joshi, Peter K., Kamatani, Yoichiro, Kanai, Masahiro, Kastarinen, Mika, Khor, Chiea Chuen, Kiess, Wieland, Kleber, Marcus E., Körner, Antje, Kovacs, Peter, Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K., Kuokkanen, Mikko, Kähönen, Mika, Lange, Leslie A., Lash, James P., Lehtimäki, Terho, Li, Hengtong, Lin, Bridget M., Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K. E., Martin, Nicholas G., Matsuda, Koichi, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mychaleckyj, Josyf C., März, Winfried, Nauck, Matthias, Nikus, Kjell, Nolte, Ilja M., Noordam, Raymond, Okada, Yukinori, Olafsson, Isleifur, Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Perola, Markus, Pirastu, Nicola, Polasek, Ozren, Porteous, David J., Poulain, Tanja, Psaty, Bruce M., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Rasheed, Humaira, Reilly, Dermot F., Rice, Kenneth M., Richmond, Anne, Ridker, Paul M., Rotter, Jerome I., Rudan, Igor, Sabanayagam, Charumathi, Salomaa, Veikko, Schneiderman, Neil, Schöttker, Ben, Sims, Mario, Snieder, Harold, Stark, Klaus J., Stefansson, Kari, Stocker, Hannah, Stumvoll, Michael, Sulem, Patrick, Sveinbjornsson, Gardar, Svensson, Per O., Tai, E-Shyong, Taylor, Kent D., Tayo, Bamidele O., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomas, Laurent F., Tremblay, Johanne, Tönjes, Anke, van der Most, Peter J., Vitart, Veronique, Völker, Uwe, Wang, Ya Xing, Wang, Chaolong, Wei, Wen Bin, Whitfield, John B., Wild, Sarah H., Wilson, James F., Winkler, Thomas W., Wong, Tien-Yin, Woodward, Mark, Sim, Xueling, Chu, Audrey Y., Feitosa, Mary F., Thorsteinsdottir, Unnur, Hung, Adriana M., Teumer, Alexander, Franceschini, Nora, Parsa, Afshin, Köttgen, Anna, Schlosser, Pascal, and Pattaro, Cristian
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- 2024
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5. Pleiotropic QTL on Chromosome 12q23-q24 Influences Triglyceride and High-Density Lipoprotein Cholesterol Levels: The HERITAGE Family Study
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Feitosa, Mary F, Rice, Treva, Borecki, Ingrid B, Rankinen, Tuomo, Leon, Arthur S, Skinner, James S., Després, Jean-Pierre, Blangero, John, Bouchard, Claude, and Rao, D. C. (Dabeeru C.)
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- 2006
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6. Glutathione S-Transferase M1 (GSTM1) and T1 (GSTT1) Polymorphisms in a Brazilian Mixed Population
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Hatagima, Ana, Marques, Christiane F. S, Krieger, Henrique, and Feitosa, Mary F
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- 2005
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7. A metabolomic signature of the APOE2 allele
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Sebastiani, Paola, Song, Zeyuan, Ellis, Dylan, Tian, Qu, Schwaiger-Haber, Michaela, Stancliffe, Ethan, Lustgarten, Michael S, Funk, Cory C, Baloni, Priyanka, Yao, Cong-Hui, Joshi, Shakchhi, Marron, Megan M, Gurinovich, Anastasia, Li, Mengze, Leshchyk, Anastasia, Xiang, Qingyan, Andersen, Stacy L, Feitosa, Mary F, Ukraintseva, Svetlana, Soerensen, Mette, Fiehn, Oliver, Ordovas, Jose M, Haigis, Marcia, Monti, Stefano, Barzilai, Nir, Milman, Sofiya, Ferrucci, Luigi, Rappaport, Noa, Patti, Gary J, and Perls, Thomas T
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Medical Biochemistry and Metabolomics ,Biomedical and Clinical Sciences ,Genetics ,Aging ,Aged ,80 and over ,Humans ,Apolipoprotein E2 ,Polymorphism ,Genetic ,Alleles ,Longitudinal Studies ,Apolipoproteins E ,Apolipoprotein E ,Longevity ,Metabolomics ,Lipid metabolism ,Clinical sciences - Abstract
With the goal of identifying metabolites that significantly correlate with the protective e2 allele of the apolipoprotein E (APOE) gene, we established a consortium of five studies of healthy aging and extreme human longevity with 3545 participants. This consortium includes the New England Centenarian Study, the Baltimore Longitudinal Study of Aging, the Arivale study, the Longevity Genes Project/LonGenity studies, and the Long Life Family Study. We analyzed the association between APOE genotype groups E2 (e2e2 and e2e3 genotypes, N = 544), E3 (e3e3 genotypes, N = 2299), and E4 (e3e4 and e4e4 genotypes, N = 702) with metabolite profiles in the five studies and used fixed effect meta-analysis to aggregate the results. Our meta-analysis identified a signature of 19 metabolites that are significantly associated with the E2 genotype group at FDR
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- 2023
8. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.
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Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer, Bartz, Traci, Bentley, Amy, Bielak, Lawrence, Chong, Mike, Chu, Audrey, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne, Haller, Toomas, Hartwig, Fernando, Hillis, David, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne, Johansson, Åsa, Jørgensen, Anja, Kaakinen, Marika, Karlsson, Robert, Kerr, Kathleen, Kim, Boram, Koolhaas, Chantal, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca, Rivera, Natalia, Robiou-du-Pont, Sebastien, Schraut, Katharina, Schulz, Christina-Alexandra, Stringham, Heather, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter, Vanmunster, Mathias, van Rooij, Frank, van Vliet-Ostaptchouk, Jana, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie, Baumeister, Sebastian, Beilby, John, Blangero, John, Boomsma, Dorret, Brage, Soren, Braund, Peter, Brody, Jennifer, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John, Collins, Francis, Cupples, L, Esko, Tõnu, Enroth, Stefan, Faul, Jessica, Fernandez-Rhodes, Lindsay, Fohner, Alison, Franco, Oscar, Galesloot, Tessel, Gordon, Scott, Grarup, Niels, Hartman, Catharina, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas, Koh, Woon-Puay, and Kolcic, Ivana
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Actinin ,Cross-Sectional Studies ,Exercise ,Genome-Wide Association Study ,Humans ,Leisure Activities ,Sedentary Behavior - Abstract
Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.
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- 2022
9. Genetic insights into resting heart rate and its role in cardiovascular disease
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van de Vegte, Yordi J., Eppinga, Ruben N., van der Ende, M. Yldau, Hagemeijer, Yanick P., Mahendran, Yuvaraj, Salfati, Elias, Smith, Albert V., Tan, Vanessa Y., Arking, Dan E., Ntalla, Ioanna, Appel, Emil V., Schurmann, Claudia, Brody, Jennifer A., Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing Hua, Isaacs, Aaron, Wang, Lihua, Luan, Jian’an, Hwang, Shih-Jen, Mononen, Nina, Auro, Kirsi, Jackson, Anne U., Bielak, Lawrence F., Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Müller-Nurasyid, Martina, Roselli, Carolina, Zhang, Weihua, Kleber, Marcus E., Guo, Xiuqing, Lin, Henry J., Pavani, Francesca, Galesloot, Tessel E., Noordam, Raymond, Milaneschi, Yuri, Schraut, Katharina E., den Hoed, Marcel, Degenhardt, Frauke, Trompet, Stella, van den Berg, Marten E., Pistis, Giorgio, Tham, Yih-Chung, Weiss, Stefan, Sim, Xueling S., Li, Hengtong L., van der Most, Peter J., Nolte, Ilja M., Lyytikäinen, Leo-Pekka, Said, M. Abdullah, Witte, Daniel R., Iribarren, Carlos, Launer, Lenore, Ring, Susan M., de Vries, Paul S., Sever, Peter, Linneberg, Allan, Bottinger, Erwin P., Padmanabhan, Sandosh, Psaty, Bruce M., Sotoodehnia, Nona, Kolcic, Ivana, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Balkau, Beverley, Silva, Claudia T., Newton-Cheh, Christopher H., Nikus, Kjell, Salo, Perttu, Mohlke, Karen L., Peyser, Patricia A., Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari, Rao, Dabeeru C., Cornelis, Marilyn C., Faul, Jessica D., Smith, Jennifer A., Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria Pina, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie, Sinner, Moritz F., Strauch, Konstantin, Delgado, Graciela E., Taylor, Kent D., Yao, Jie, Foco, Luisa, Melander, Olle, de Graaf, Jacqueline, de Mutsert, Renée, de Geus, Eco J. C., Johansson, Åsa, Joshi, Peter K., Lind, Lars, Franke, Andre, Macfarlane, Peter W., Tarasov, Kirill V., Tan, Nicholas, Felix, Stephan B., Tai, E-Shyong, Quek, Debra Q., Snieder, Harold, Ormel, Johan, Ingelsson, Martin, Lindgren, Cecilia, Morris, Andrew P., Raitakari, Olli T., Hansen, Torben, Assimes, Themistocles, Gudnason, Vilmundur, Timpson, Nicholas J., Morrison, Alanna C., Munroe, Patricia B., Strachan, David P., Grarup, Niels, Loos, Ruth J. F., Heckbert, Susan R., Vollenweider, Peter, Hayward, Caroline, Stefansson, Kari, Froguel, Philippe, Groop, Leif, Wareham, Nicholas J., van Duijn, Cornelia M., Feitosa, Mary F., O’Donnell, Christopher J., Kähönen, Mika, Perola, Markus, Boehnke, Michael, Kardia, Sharon L. R., Erdmann, Jeanette, Palmer, Colin N. A., Ohlsson, Claes, Porteous, David J., Eriksson, Johan G., Bouchard, Claude, Moebus, Susanne, Kraft, Peter, Weir, David R., Cusi, Daniele, Ferrucci, Luigi, Ulivi, Sheila, Girotto, Giorgia, Correa, Adolfo, Kääb, Stefan, Peters, Annette, Chambers, John C., Kooner, Jaspal S., März, Winfried, Rotter, Jerome I., Hicks, Andrew A., Smith, J. Gustav, Kiemeney, Lambertus A. L. M., Mook-Kanamori, Dennis O., Penninx, Brenda W. J. H., Gyllensten, Ulf, Wilson, James F., Burgess, Stephen, Sundström, Johan, Lieb, Wolfgang, Jukema, J. Wouter, Eijgelsheim, Mark, Lakatta, Edward L. M., Cheng, Ching-Yu, Dörr, Marcus, Wong, Tien-Yin, Sabanayagam, Charumathi, Oldehinkel, Albertine J., Riese, Harriette, Lehtimäki, Terho, Verweij, Niek, and van der Harst, Pim
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- 2023
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10. Systemic inflammation in relation to exceptional memory in the Long Life Family Study (LLFS)
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Patel, Ruhee, Cosentino, Stephanie, Zheng, Esther Zhiwei, Schupf, Nicole, Barral, Sandra, Feitosa, Mary, Andersen, Stacy L., Sebastiani, Paola, Ukraintseva, Svetlana, Christensen, Kaare, Zmuda, Joseph, Thyagarajan, Bharat, and Gu, Yian
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- 2024
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11. Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol.
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Wu, Peitao, Moon, Jee-Young, Daghlas, Iyas, Franco, Giulianini, Porneala, Bianca, Ahmadizar, Fariba, Richardson, Tom, Isaksen, Jonas, Hindy, Georgy, Yao, Jie, Sitlani, Colleen, Raffield, Laura, Yanek, Lisa, Feitosa, Mary, Cuadrat, Rafael, Qi, Qibin, Arfan Ikram, M, Ellervik, Christina, Ericson, Ulrika, Goodarzi, Mark, Brody, Jennifer, Lange, Leslie, Mercader, Josep, Vaidya, Dhananjay, An, Ping, Schulze, Matthias, Masana, Lluis, Ghanbari, Mohsen, Olesen, Morten, Cai, Jianwen, Guo, Xiuqing, Floyd, James, Jäger, Susanne, Province, Michael, Kalyani, Rita, Psaty, Bruce, Orho-Melander, Marju, Ridker, Paul, Kanters, Jørgen, Uitterlinden, Andre, Davey Smith, George, Gill, Dipender, Kaplan, Robert, Kavousi, Maryam, Raghavan, Sridharan, Chasman, Daniel, Rotter, Jerome, Meigs, James, Florez, Jose, Dupuis, Josée, Liu, Ching-Ti, and Merino, Jordi
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Cholesterol ,LDL ,Diabetes Mellitus ,Type 2 ,Genome-Wide Association Study ,Humans ,Mendelian Randomization Analysis ,Obesity ,Risk Factors - Abstract
OBJECTIVE: LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown. RESEARCH DESIGN AND METHODS: We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses. RESULTS: A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95% CI 1.01, 1.24]) and BMI (β = 0.07 SD units [95% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95% CI 1.01, 1.08]) with a proportion mediated of 38% of the total effect (P = 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8% (P = 0.04). CONCLUSIONS: These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications.
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- 2022
12. Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes
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Lu, Yingchang, Dimitrov, Latchezar, Chen, Shyh-Huei, Bielak, Lawrence F, Bis, Joshua C, Feitosa, Mary F, Lu, Lingyi, Kavousi, Maryam, Raffield, Laura M, Smith, Albert V, Wang, Lihua, Weiss, Stefan, Yao, Jie, Zhu, Jiaxi, Gudmundsson, Elias F, Gudmundsdottir, Valborg, Bos, Daniel, Ghanbari, Mohsen, Ikram, M Arfan, Hwang, Shih-Jen, Taylor, Kent D, Budoff, Matthew J, Gíslason, Gauti K, O’Donnell, Christopher J, An, Ping, Franceschini, Nora, Freedman, Barry I, Fu, Yi-Ping, Guo, Xiuqing, Heiss, Gerardo, Kardia, Sharon LR, Wilson, James G, Langefeld, Carl D, Schminke, Ulf, Uitterlinden, André G, Lange, Leslie A, Peyser, Patricia A, Gudnason, Vilmundur G, Psaty, Bruce M, Rotter, Jerome I, Bowden, Donald W, and Ng, Maggie CY
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Genetics ,Diabetes ,Biotechnology ,Heart Disease ,Atherosclerosis ,Biomedical Imaging ,Aging ,Prevention ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Black People ,Diabetes Complications ,Diabetes Mellitus ,Type 2 ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,White People ,atherosclerosis ,carotid intima-media thickness ,coronary artery disease ,genetics ,genome-wide association study ,Medical Biotechnology ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundCoronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.MethodsWe performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.ResultsWe replicated 2 loci (rs9369640 and rs9349379 near PHACTR1 and rs10757278 near CDKN2B) for CAC and one locus for cIMT (rs7412 and rs445925 near APOE-APOC1) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near CSNK1A1L/LINC00547/POSTN at 13q13.3) at P=2.0×10-8 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints POSTN, encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (P
- Published
- 2021
13. Allele-specific variation at APOE increases nonalcoholic fatty liver disease and obesity but decreases risk of Alzheimer’s disease and myocardial infarction
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Palmer, Nicholette D, Kahali, Bratati, Kuppa, Annapurna, Chen, Yanhua, Du, Xiaomeng, Feitosa, Mary F, Bielak, Lawrence F, O’Connell, Jeffrey R, Musani, Solomon K, Guo, Xiuqing, Smith, Albert V, Ryan, Kathleen A, Eirksdottir, Gudny, Allison, Matthew A, Bowden, Donald W, Budoff, Matthew J, Carr, J Jeffrey, Chen, Yii-Der I, Taylor, Kent D, Correa, Adolfo, Crudup, Breland F, Halligan, Brian, Yang, Jian, Kardia, Sharon LR, Launer, Lenore J, Fu, Yi-Ping, Mosley, Thomas H, Norris, Jill M, Terry, James G, O’Donnell, Christopher J, Rotter, Jerome I, Wagenknecht, Lynne E, Gudnason, Vilmundur, Province, Michael A, Peyser, Patricia A, and Speliotes, Elizabeth K
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Biological Sciences ,Genetics ,Digestive Diseases ,Brain Disorders ,Prevention ,Aging ,Chronic Liver Disease and Cirrhosis ,Obesity ,Neurosciences ,Alzheimer's Disease ,Liver Disease ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Acquired Cognitive Impairment ,Neurodegenerative ,Human Genome ,Hepatitis ,Dementia ,2.1 Biological and endogenous factors ,Aetiology ,Oral and gastrointestinal ,Alanine Transaminase ,Alleles ,Alzheimer Disease ,Apolipoproteins E ,Databases ,Genetic ,Exome ,Gene Frequency ,Genome-Wide Association Study ,Humans ,Liver ,Liver Cirrhosis ,Myocardial Infarction ,Non-alcoholic Fatty Liver Disease ,Phenotype ,Polymorphism ,Single Nucleotide ,Prognosis ,Risk Factors ,Triglycerides ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is highly correlated with metabolic disease. NAFLD results from environmental exposures acting on a susceptible polygenic background. This study performed the largest multiethnic investigation of exonic variation associated with NAFLD and correlated metabolic traits and diseases. An exome array meta-analysis was carried out among eight multiethnic population-based cohorts (n = 16 492) with computed tomography (CT) measured hepatic steatosis. A fixed effects meta-analysis identified five exome-wide significant loci (P
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- 2021
14. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.
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de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, and Kavousi, Maryam
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Lifelines Cohort Study ,Psychiatry ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences - Abstract
Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P
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- 2021
15. Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry
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Graff, Mariaelisa, Justice, Anne E, Young, Kristin L, Marouli, Eirini, Zhang, Xinruo, Fine, Rebecca S, Lim, Elise, Buchanan, Victoria, Rand, Kristin, Feitosa, Mary F, Wojczynski, Mary K, Yanek, Lisa R, Shao, Yaming, Rohde, Rebecca, Adeyemo, Adebowale A, Aldrich, Melinda C, Allison, Matthew A, Ambrosone, Christine B, Ambs, Stefan, Amos, Christopher, Arnett, Donna K, Atwood, Larry, Bandera, Elisa V, Bartz, Traci, Becker, Diane M, Berndt, Sonja I, Bernstein, Leslie, Bielak, Lawrence F, Blot, William J, Bottinger, Erwin P, Bowden, Donald W, Bradfield, Jonathan P, Brody, Jennifer A, Broeckel, Ulrich, Burke, Gregory, Cade, Brian E, Cai, Qiuyin, Caporaso, Neil, Carlson, Chris, Carpten, John, Casey, Graham, Chanock, Stephen J, Chen, Guanjie, Chen, Minhui, Chen, Yii-Der I, Chen, Wei-Min, Chesi, Alessandra, Chiang, Charleston WK, Chu, Lisa, Coetzee, Gerry A, Conti, David V, Cooper, Richard S, Cushman, Mary, Demerath, Ellen, Deming, Sandra L, Dimitrov, Latchezar, Ding, Jingzhong, Diver, W Ryan, Duan, Qing, Evans, Michele K, Falusi, Adeyinka G, Faul, Jessica D, Fornage, Myriam, Fox, Caroline, Freedman, Barry I, Garcia, Melissa, Gillanders, Elizabeth M, Goodman, Phyllis, Gottesman, Omri, Grant, Struan FA, Guo, Xiuqing, Hakonarson, Hakon, Haritunians, Talin, Harris, Tamara B, Harris, Curtis C, Henderson, Brian E, Hennis, Anselm, Hernandez, Dena G, Hirschhorn, Joel N, McNeill, Lorna Haughton, Howard, Timothy D, Howard, Barbara, Hsing, Ann W, Hsu, Yu-Han H, Hu, Jennifer J, Huff, Chad D, Huo, Dezheng, Ingles, Sue A, Irvin, Marguerite R, John, Esther M, Johnson, Karen C, Jordan, Joanne M, Kabagambe, Edmond K, Kang, Sun J, Kardia, Sharon L, Keating, Brendan J, Kittles, Rick A, Klein, Eric A, Kolb, Suzanne, and Kolonel, Laurence N
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Human Genome ,Genetics ,Africa ,Black or African American ,Black People ,Body Height ,Europe ,Female ,Genome-Wide Association Study ,Humans ,Male ,Polymorphism ,Single Nucleotide ,African ancestry ,fine-mapping ,genome-wide ,height ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
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- 2021
16. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
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Gorski, Mathias, Jung, Bettina, Li, Yong, Matias-Garcia, Pamela R, Wuttke, Matthias, Coassin, Stefan, Thio, Chris HL, Kleber, Marcus E, Winkler, Thomas W, Wanner, Veronika, Chai, Jin-Fang, Chu, Audrey Y, Cocca, Massimiliano, Feitosa, Mary F, Ghasemi, Sahar, Hoppmann, Anselm, Horn, Katrin, Li, Man, Nutile, Teresa, Scholz, Markus, Sieber, Karsten B, Teumer, Alexander, Tin, Adrienne, Wang, Judy, Tayo, Bamidele O, Ahluwalia, Tarunveer S, Almgren, Peter, Bakker, Stephan JL, Banas, Bernhard, Bansal, Nisha, Biggs, Mary L, Boerwinkle, Eric, Bottinger, Erwin P, Brenner, Hermann, Carroll, Robert J, Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Coresh, Josef, de Borst, Martin H, Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Franke, Andre, Freitag-Wolf, Sandra, Gampawar, Piyush, Gansevoort, Ron T, Ghanbari, Mohsen, Gieger, Christian, Hamet, Pavel, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Foo, Valencia Hui Xian, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Ikram, M Arfan, Josyula, Navya Shilpa, Kähönen, Mika, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K, Kühnel, Brigitte, Lange, Leslie A, Lehtimäki, Terho, Lieb, Wolfgang, Loos, Ruth JF, Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P, Mononen, Nina, Mychaleckyj, Josyf C, Nadkarni, Girish N, Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M, O’Donoghue, Michelle L, Orho-Melander, Marju, Pendergrass, Sarah A, Penninx, Brenda WJH, Preuss, Michael H, Psaty, Bruce M, Raffield, Laura M, Raitakari, Olli T, Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M, Rosenkranz, Alexander R, Rossing, Peter, Rotter, Jerome I, Sabanayagam, Charumathi, Schmidt, Helena, and Schmidt, Reinhold
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Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Human Genome ,Kidney Disease ,Rare Diseases ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Renal and urogenital ,AMP-Activated Protein Kinases ,Creatinine ,Genome-Wide Association Study ,Glomerular Filtration Rate ,Humans ,Kidney ,Protein Disulfide-Isomerases ,United Kingdom ,acute kidney injury ,end-stage kidney disease ,genome-wide association study ,rapid eGFRcrea decline ,Lifelines Cohort Study ,Regeneron Genetics Center ,Urology & Nephrology ,Clinical sciences - Abstract
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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- 2021
17. Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity
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Yaghootkar, Hanieh, Zhang, Yiying, Spracklen, Cassandra N, Karaderi, Tugce, Huang, Lam Opal, Bradfield, Jonathan, Schurmann, Claudia, Fine, Rebecca S, Preuss, Michael H, Kutalik, Zoltan, Wittemans, Laura BL, Lu, Yingchang, Metz, Sophia, Willems, Sara M, Li-Gao, Ruifang, Grarup, Niels, Wang, Shuai, Molnos, Sophie, Sandoval-Zárate, América A, Nalls, Mike A, Lange, Leslie A, Haesser, Jeffrey, Guo, Xiuqing, Lyytikäinen, Leo-Pekka, Feitosa, Mary F, Sitlani, Colleen M, Venturini, Cristina, Mahajan, Anubha, Kacprowski, Tim, Wang, Carol A, Chasman, Daniel I, Amin, Najaf, Broer, Linda, Robertson, Neil, Young, Kristin L, Allison, Matthew, Auer, Paul L, Blüher, Matthias, Borja, Judith B, Bork-Jensen, Jette, Carrasquilla, Germán D, Christofidou, Paraskevi, Demirkan, Ayse, Doege, Claudia A, Garcia, Melissa E, Graff, Mariaelisa, Guo, Kaiying, Hakonarson, Hakon, Hong, Jaeyoung, Ida Chen, Yii-Der, Jackson, Rebecca, Jakupović, Hermina, Jousilahti, Pekka, Justice, Anne E, Kähönen, Mika, Kizer, Jorge R, Kriebel, Jennifer, LeDuc, Charles A, Li, Jin, Lind, Lars, Luan, Jian'an, Mackey, David A, Mangino, Massimo, Männistö, Satu, Martin Carli, Jayne F, Medina-Gomez, Carolina, Mook-Kanamori, Dennis O, Morris, Andrew P, de Mutsert, Renée, Nauck, Matthias, Prokic, Ivana, Pennell, Craig E, Pradhan, Arund D, Psaty, Bruce M, Raitakari, Olli T, Scott, Robert A, Skaaby, Tea, Strauch, Konstantin, Taylor, Kent D, Teumer, Alexander, Uitterlinden, Andre G, Wu, Ying, Yao, Jie, Walker, Mark, North, Kari E, Kovacs, Peter, Ikram, M Arfan, van Duijn, Cornelia M, Ridker, Paul M, Lye, Stephen, Homuth, Georg, Ingelsson, Erik, Spector, Tim D, McKnight, Barbara, Province, Michael A, Lehtimäki, Terho, Adair, Linda S, Rotter, Jerome I, Reiner, Alexander P, and Wilson, James G
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Genetics ,Nutrition ,Prevention ,Obesity ,Aetiology ,2.1 Biological and endogenous factors ,Oral and gastrointestinal ,Metabolic and endocrine ,Cardiovascular ,Stroke ,Cancer ,Adiposity ,Gene Expression Regulation ,Developmental ,Genetic Variation ,Genotype ,Humans ,Leptin ,Models ,Molecular ,Protein Conformation ,Racial Groups ,Medical and Health Sciences ,Endocrinology & Metabolism - Abstract
Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
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- 2020
18. Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels
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Wang, Zhe, Chen, Han, Bartz, Traci M, Bielak, Lawrence F, Chasman, Daniel I, Feitosa, Mary F, Franceschini, Nora, Guo, Xiuqing, Lim, Elise, Noordam, Raymond, Richard, Melissa A, Wang, Heming, Cade, Brian, Cupples, L Adrienne, de Vries, Paul S, Giulanini, Franco, Lee, Jiwon, Lemaitre, Rozenn N, Martin, Lisa W, Reiner, Alex P, Rich, Stephen S, Schreiner, Pamela J, Sidney, Stephen, Sitlani, Colleen M, Smith, Jennifer A, van Dijk, Ko Willems, Yao, Jie, Zhao, Wei, Fornage, Myriam, Kardia, Sharon LR, Kooperberg, Charles, Liu, Ching-Ti, Mook-Kanamori, Dennis O, Province, Michael A, Psaty, Bruce M, Redline, Susan, Ridker, Paul M, Rotter, Jerome I, Boerwinkle, Eric, Morrison, Alanna C, and Group, on behalf of the CHARGE Gene-Lifestyle Interactions Working
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Substance Misuse ,Human Genome ,Genetics ,Cardiovascular ,Heart Disease ,Alcoholism ,Alcohol Use and Health ,Aetiology ,2.1 Biological and endogenous factors ,Stroke ,Cancer ,Oral and gastrointestinal ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Alcohol Drinking ,Apolipoproteins E ,Cholesterol ,HDL ,Female ,Gene Frequency ,Genetic Loci ,Genome-Wide Association Study ,Humans ,Lipids ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Proprotein Convertase 9 ,Triglycerides ,White People ,Young Adult ,exome ,gene-environment interaction ,genome-wide association study ,lipids ,self-report ,CHARGE Gene-Lifestyle Interactions Working Group ,Medical Biotechnology ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundAlcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels.MethodsIn the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered.ResultsWe discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (PCSK9, LPA, LPL, LIPG, ANGPTL4, APOB, APOC3, and CD300LG) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered (P=6.65×10-6 for the interaction test) and replicated at nominal significance level (P=0.013) in SMC5.ConclusionsIn conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.
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- 2020
19. Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose
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Wu, Peitao, Rybin, Denis, Bielak, Lawrence F, Feitosa, Mary F, Franceschini, Nora, Li, Yize, Lu, Yingchang, Marten, Jonathan, Musani, Solomon K, Noordam, Raymond, Raghavan, Sridharan, Rose, Lynda M, Schwander, Karen, Smith, Albert V, Tajuddin, Salman M, Vojinovic, Dina, Amin, Najaf, Arnett, Donna K, Bottinger, Erwin P, Demirkan, Ayse, Florez, Jose C, Ghanbari, Mohsen, Harris, Tamara B, Launer, Lenore J, Liu, Jingmin, Liu, Jun, Mook-Kanamori, Dennis O, Murray, Alison D, Nalls, Mike A, Peyser, Patricia A, Uitterlinden, André G, Voortman, Trudy, Bouchard, Claude, Chasman, Daniel, Correa, Adolfo, de Mutsert, Renée, Evans, Michele K, Gudnason, Vilmundur, Hayward, Caroline, Kao, Linda, Kardia, Sharon LR, Kooperberg, Charles, Loos, Ruth JF, Province, Michael M, Rankinen, Tuomo, Redline, Susan, Ridker, Paul M, Rotter, Jerome I, Siscovick, David, Smith, Blair H, van Duijn, Cornelia, Zonderman, Alan B, Rao, DC, Wilson, James G, Dupuis, Josée, Meigs, James B, Liu, Ching-Ti, and Vassy, Jason L
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Epidemiology ,Health Sciences ,Pharmacology and Pharmaceutical Sciences ,Tobacco ,Aging ,Tobacco Smoke and Health ,Human Genome ,Nutrition ,Diabetes ,Clinical Research ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Adult ,Aged ,Black People ,Blood Glucose ,Cigarette Smoking ,Cohort Studies ,Diabetes Mellitus ,Type 2 ,Fasting ,Feasibility Studies ,Female ,Genetic Loci ,Genome-Wide Association Study ,Genotype ,Humans ,Incidence ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Risk ,White People ,General Science & Technology - Abstract
Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p
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- 2020
20. Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
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Hahn, Julie, Fu, Yi-Ping, Brown, Michael R, Bis, Joshua C, de Vries, Paul S, Feitosa, Mary F, Yanek, Lisa R, Weiss, Stefan, Giulianini, Franco, Smith, Albert Vernon, Guo, Xiuqing, Bartz, Traci M, Becker, Diane M, Becker, Lewis C, Boerwinkle, Eric, Brody, Jennifer A, Chen, Yii-Der Ida, Franco, Oscar H, Grove, Megan, Harris, Tamara B, Hofman, Albert, Hwang, Shih-Jen, Kral, Brian G, Launer, Lenore J, Markus, Marcello RP, Rice, Kenneth M, Rich, Stephen S, Ridker, Paul M, Rivadeneira, Fernando, Rotter, Jerome I, Sotoodehnia, Nona, Taylor, Kent D, Uitterlinden, André G, Völker, Uwe, Völzke, Henry, Yao, Jie, Chasman, Daniel I, Dörr, Marcus, Gudnason, Vilmundur, Mathias, Rasika A, Post, Wendy, Psaty, Bruce M, Dehghan, Abbas, O’Donnell, Christopher J, and Morrison, Alanna C
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Human Genome ,Aging ,Clinical Research ,Cardiovascular ,2.4 Surveillance and distribution ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Coronary Artery Disease ,Cross-Sectional Studies ,Europe ,Genetic Loci ,Genome-Wide Association Study ,Humans ,Myocardial Infarction ,Polymorphism ,Single Nucleotide ,Prospective Studies ,White People ,General Science & Technology - Abstract
BackgroundGenome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome.Methods and resultsUsing samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event.ConclusionThis study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.
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- 2020
21. Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium
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Merino, Jordi, Dashti, Hassan S, Li, Sherly X, Sarnowski, Chloé, Justice, Anne E, Graff, Misa, Papoutsakis, Constantina, Smith, Caren E, Dedoussis, George V, Lemaitre, Rozenn N, Wojczynski, Mary K, Männistö, Satu, Ngwa, Julius S, Kho, Minjung, Ahluwalia, Tarunveer S, Pervjakova, Natalia, Houston, Denise K, Bouchard, Claude, Huang, Tao, Orho-Melander, Marju, Frazier-Wood, Alexis C, Mook-Kanamori, Dennis O, Pérusse, Louis, Pennell, Craig E, de Vries, Paul S, Voortman, Trudy, Li, Olivia, Kanoni, Stavroula, Rose, Lynda M, Lehtimäki, Terho, Zhao, Jing Hua, Feitosa, Mary F, Luan, Jian’an, McKeown, Nicola M, Smith, Jennifer A, Hansen, Torben, Eklund, Niina, Nalls, Mike A, Rankinen, Tuomo, Huang, Jinyan, Hernandez, Dena G, Schulz, Christina-Alexandra, Manichaikul, Ani, Li-Gao, Ruifang, Vohl, Marie-Claude, Wang, Carol A, van Rooij, Frank JA, Shin, Jean, Kalafati, Ioanna P, Day, Felix, Ridker, Paul M, Kähönen, Mika, Siscovick, David S, Langenberg, Claudia, Zhao, Wei, Astrup, Arne, Knekt, Paul, Garcia, Melissa, Rao, DC, Qi, Qibin, Ferrucci, Luigi, Ericson, Ulrika, Blangero, John, Hofman, Albert, Pausova, Zdenka, Mikkilä, Vera, Wareham, Nick J, Kardia, Sharon LR, Pedersen, Oluf, Jula, Antti, Curran, Joanne E, Zillikens, M Carola, Viikari, Jorma S, Forouhi, Nita G, Ordovás, José M, Lieske, John C, Rissanen, Harri, Uitterlinden, André G, Raitakari, Olli T, Kiefte-de Jong, Jessica C, Dupuis, Josée, Rotter, Jerome I, North, Kari E, Scott, Robert A, Province, Michael A, Perola, Markus, Cupples, L Adrienne, Turner, Stephen T, Sørensen, Thorkild IA, Salomaa, Veikko, Liu, Yongmei, Sung, Yun J, Qi, Lu, Bandinelli, Stefania, Rich, Stephen S, de Mutsert, Renée, Tremblay, Angelo, Oddy, Wendy H, Franco, Oscar H, and Paus, Tomas
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Biomedical and Clinical Sciences ,Clinical Sciences ,Obesity ,Human Genome ,Genetics ,Prevention ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Cardiovascular ,Metabolic and endocrine ,Aged ,Aging ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Cohort Studies ,Energy Intake ,Female ,Fibroblast Growth Factors ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genomics ,Genotype ,Heart Diseases ,Humans ,Male ,Membrane Proteins ,Middle Aged ,Nutrients ,Polymorphism ,Single Nucleotide ,Receptors ,Retinoic Acid ,White People ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Clinical sciences ,Biological psychology ,Clinical and health psychology - Abstract
Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P
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- 2019
22. 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, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, 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, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., 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 J. F., 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., and Hirschhorn, Joel N.
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- 2022
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23. Physical resilience after a diagnosis of cardiovascular disease among offspring of long-lived siblings
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Galvin, Angéline, Feitosa, Mary, Arbeev, Konstantin, Kuipers, Allison L., Wojczynski, Mary, Ukrainsteva, Svetlana, and Christensen, Kaare
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- 2022
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24. Gene-lifestyle interactions in the genomics of human complex traits
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Laville, Vincent, Majarian, Timothy, Sung, Yun J., Schwander, Karen, Feitosa, Mary F., Chasman, Daniel I., Bentley, Amy R., Rotimi, Charles N., Cupples, L. Adrienne, de Vries, Paul S., Brown, Michael R., Morrison, Alanna C., Kraja, Aldi T., Province, Mike, Gu, C. Charles, Gauderman, W. James, Rao, D. C., Manning, Alisa K., and Aschard, Hugues
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- 2022
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25. Association of leukocyte telomere length with perceived physical fatigability
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Katz, Rain, Gay, Emma L., Kuipers, Allison L., Lee, Joseph H., Honig, Lawrence S., Christensen, Kaare, Feitosa, Mary F., Wojczynski, Mary K., and Glynn, Nancy W.
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- 2022
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26. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.
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Noordam, Raymond, Bos, Maxime M, Wang, Heming, Winkler, Thomas W, Bentley, Amy R, Kilpeläinen, Tuomas O, de Vries, Paul S, Sung, Yun Ju, Schwander, Karen, Cade, Brian E, Manning, Alisa, Aschard, Hugues, Brown, Michael R, Chen, Han, Franceschini, Nora, Musani, Solomon K, Richard, Melissa, Vojinovic, Dina, Aslibekyan, Stella, Bartz, Traci M, de Las Fuentes, Lisa, Feitosa, Mary, Horimoto, Andrea R, Ilkov, Marjan, Kho, Minjung, Kraja, Aldi, Li, Changwei, Lim, Elise, Liu, Yongmei, Mook-Kanamori, Dennis O, Rankinen, Tuomo, Tajuddin, Salman M, van der Spek, Ashley, Wang, Zhe, Marten, Jonathan, Laville, Vincent, Alver, Maris, Evangelou, Evangelos, Graff, Maria E, He, Meian, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Marques-Vidal, Pedro, Nolte, Ilja M, Palmer, Nicholette D, Rauramaa, Rainer, Shu, Xiao-Ou, Snieder, Harold, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Adolfo, Correa, Ballantyne, Christie, Bielak, Larry, Biermasz, Nienke R, Boerwinkle, Eric, Dimou, Niki, Eiriksdottir, Gudny, Gao, Chuan, Gharib, Sina A, Gottlieb, Daniel J, Haba-Rubio, José, Harris, Tamara B, Heikkinen, Sami, Heinzer, Raphaël, Hixson, James E, Homuth, Georg, Ikram, M Arfan, Komulainen, Pirjo, Krieger, Jose E, Lee, Jiwon, Liu, Jingmin, Lohman, Kurt K, Luik, Annemarie I, Mägi, Reedik, Martin, Lisa W, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Nalls, Mike A, O'Connell, Jeff, Peters, Annette, Peyser, Patricia, Raitakari, Olli T, Reiner, Alex P, Rensen, Patrick CN, Rice, Treva K, Rich, Stephen S, Roenneberg, Till, Rotter, Jerome I, Schreiner, Pamela J, Shikany, James, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Sofer, Tamar, Strauch, Konstantin, Swertz, Morris A, Taylor, Kent D, and Uitterlinden, André G
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Humans ,Lipids ,Chromosome Mapping ,Sleep ,Phylogeny ,Polymorphism ,Single Nucleotide ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Young Adult ,Genetic Loci ,Polymorphism ,Single Nucleotide ,and over - Abstract
Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
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- 2019
27. HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype
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Malhotra, Rajeev, Mauer, Andreas C, Lino Cardenas, Christian L, Guo, Xiuqing, Yao, Jie, Zhang, Xiaoling, Wunderer, Florian, Smith, Albert V, Wong, Quenna, Pechlivanis, Sonali, Hwang, Shih-Jen, Wang, Judy, Lu, Lingyi, Nicholson, Christopher J, Shelton, Georgia, Buswell, Mary D, Barnes, Hanna J, Sigurslid, Haakon H, Slocum, Charles, Rourke, Caitlin O’, Rhee, David K, Bagchi, Aranya, Nigwekar, Sagar U, Buys, Emmanuel S, Campbell, Catherine Y, Harris, Tamara, Budoff, Matthew, Criqui, Michael H, Rotter, Jerome I, Johnson, Andrew D, Song, Ci, Franceschini, Nora, Debette, Stephanie, Hoffmann, Udo, Kälsch, Hagen, Nöthen, Markus M, Sigurdsson, Sigurdur, Freedman, Barry I, Bowden, Donald W, Jöckel, Karl-Heinz, Moebus, Susanne, Erbel, Raimund, Feitosa, Mary F, Gudnason, Vilmundur, Thanassoulis, George, Zapol, Warren M, Lindsay, Mark E, Bloch, Donald B, Post, Wendy S, and O’Donnell, Christopher J
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Biological Sciences ,Genetics ,Human Genome ,Heart Disease - Coronary Heart Disease ,Heart Disease ,Cardiovascular ,Aetiology ,2.1 Biological and endogenous factors ,Aged ,Animals ,Aorta ,Atherosclerosis ,Cohort Studies ,Female ,GTPase-Activating Proteins ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Histone Deacetylases ,Humans ,Male ,Mice ,Mice ,Inbred C57BL ,Mice ,Knockout ,Middle Aged ,Muscle Contraction ,Muscle ,Smooth ,Vascular ,Phenotype ,Polymorphism ,Single Nucleotide ,Repressor Proteins ,Vascular Calcification ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P
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- 2019
28. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria.
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Teumer, Alexander, Li, Yong, Ghasemi, Sahar, Prins, Bram P, Wuttke, Matthias, Hermle, Tobias, Giri, Ayush, Sieber, Karsten B, Qiu, Chengxiang, Kirsten, Holger, Tin, Adrienne, Chu, Audrey Y, Bansal, Nisha, Feitosa, Mary F, Wang, Lihua, Chai, Jin-Fang, Cocca, Massimiliano, Fuchsberger, Christian, Gorski, Mathias, Hoppmann, Anselm, Horn, Katrin, Li, Man, Marten, Jonathan, Noce, Damia, Nutile, Teresa, Sedaghat, Sanaz, Sveinbjornsson, Gardar, Tayo, Bamidele O, van der Most, Peter J, Xu, Yizhe, Yu, Zhi, Gerstner, Lea, Ärnlöv, Johan, Bakker, Stephan JL, Baptista, Daniela, Biggs, Mary L, Boerwinkle, Eric, Brenner, Hermann, Burkhardt, Ralph, Carroll, Robert J, Chee, Miao-Li, Chee, Miao-Ling, Chen, Mengmeng, Cheng, Ching-Yu, Cook, James P, Coresh, Josef, Corre, Tanguy, Danesh, John, de Borst, Martin H, De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko PJ, Degenhardt, Frauke, Dittrich, Katalin, Divers, Jasmin, Eckardt, Kai-Uwe, Ehret, Georg, Endlich, Karlhans, Felix, Janine F, Franco, Oscar H, Franke, Andre, Freedman, Barry I, Freitag-Wolf, Sandra, Gansevoort, Ron T, Giedraitis, Vilmantas, Gögele, Martin, Grundner-Culemann, Franziska, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hamet, Pavel, Harris, Tamara B, Hicks, Andrew A, Holm, Hilma, Foo, Valencia Hui Xian, Hwang, Shih-Jen, Ikram, M Arfan, Ingelsson, Erik, Jaddoe, Vincent WV, Jakobsdottir, Johanna, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Khor, Chiea-Chuen, Kiess, Wieland, Koenig, Wolfgang, Körner, Antje, Kovacs, Peter, Kramer, Holly, Krämer, Bernhard K, Kronenberg, Florian, Lange, Leslie A, Langefeld, Carl D, Lee, Jeannette Jen-Mai, Lehtimäki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M, Liu, Jianjun, and Loeffler, Markus
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Animals ,Humans ,Drosophila melanogaster ,Albuminuria ,Diabetes Mellitus ,Genetic Predisposition to Disease ,Creatinine ,Risk Factors ,Chromosome Mapping ,Gene Expression Regulation ,Meta-Analysis as Topic ,Genome-Wide Association Study ,Genetic Loci ,Phenomics - Abstract
Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
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- 2019
29. Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology
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Spracklen, Cassandra N, Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S, Kutalik, Zoltan, Preuss, Michael H, Lu, Yingchang, Wittemans, Laura BL, Adair, Linda S, Allison, Matthew, Amin, Najaf, Auer, Paul L, Bartz, Traci M, Blüher, Matthias, Boehnke, Michael, Borja, Judith B, Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I, Chen, Yii-Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M, Feitosa, Mary F, Garcia, Melissa E, Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B, Highland, Heather M, Hong, Jaeyoung, Ikram, M Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kähönen, Mika, Kizer, Jorge R, Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A, Lehtimäki, Terho, Li, Jin, Li-Gao, Ruifang, Lind, Lars, Luan, Jian'an, Lyytikäinen, Leo-Pekka, MacGregor, Stuart, Mackey, David A, Mahajan, Anubha, Mangino, Massimo, Männistö, Satu, McCarthy, Mark I, McKnight, Barbara, Medina-Gomez, Carolina, Meigs, James B, Molnos, Sophie, Mook-Kanamori, Dennis, Morris, Andrew P, de Mutsert, Renee, Nalls, Mike A, Nedeljkovic, Ivana, North, Kari E, Pennell, Craig E, Pradhan, Aruna D, Province, Michael A, Raitakari, Olli T, Raulerson, Chelsea K, Reiner, Alex P, Ridker, Paul M, Ripatti, Samuli, Roberston, Neil, Rotter, Jerome I, Salomaa, Veikko, Sandoval-Zárate, America A, Sitlani, Colleen M, Spector, Tim D, Strauch, Konstantin, Stumvoll, Michael, Taylor, Kent D, Thuesen, Betina, Tönjes, Anke, Uitterlinden, Andre G, Venturini, Cristina, Walker, Mark, Wang, Carol A, Wang, Shuai, Wareham, Nicholas J, Willems, Sara M, Willems van Dijk, Ko, Wilson, James G, Wu, Ying, Yao, Jie, Young, Kristin L, Langenberg, Claudia, and Frayling, Timothy M
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Nutrition ,Obesity ,2.1 Biological and endogenous factors ,Aetiology ,Metabolic and endocrine ,Cardiovascular ,Adiponectin ,Adipose Tissue ,Adolescent ,Adult ,Black or African American ,Aged ,Aged ,80 and over ,Exome ,Female ,Genetic Predisposition to Disease ,Hispanic or Latino ,Humans ,Lipids ,Male ,Middle Aged ,Phenotype ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,White People ,Young Adult ,adiponectin ,cardio metabolic traits ,exome ,genetics ,genome-wide association study ,lipids ,obesity ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.
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- 2019
30. Insulin Resistance Exacerbates Genetic Predisposition to Nonalcoholic Fatty Liver Disease in Individuals Without Diabetes
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Barata, Llilda, Feitosa, Mary F, Bielak, Lawrence F, Halligan, Brian, Baldridge, Abigail S, Guo, Xiuqing, Yerges‐Armstrong, Laura M, Smith, Albert V, Yao, Jie, Palmer, Nicholette D, VanWagner, Lisa B, Carr, J Jeffrey, Chen, Yii‐Der I, Allison, Matthew, Budoff, Matthew J, Handelman, Samuel K, Kardia, Sharon LR, Mosley, Thomas H, Ryan, Kathleen, Harris, Tamara B, Launer, Lenore J, Gudnason, Vilmundur, Rotter, Jerome I, Fornage, Myriam, Rasmussen‐Torvik, Laura J, Borecki, Ingrid B, O’Connell, Jeffrey R, Peyser, Patricia A, Speliotes, Elizabeth K, and Province, Michael A
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Biomedical and Clinical Sciences ,Clinical Sciences ,Nutrition ,Diabetes ,Prevention ,Genetics ,Chronic Liver Disease and Cirrhosis ,Digestive Diseases ,Liver Disease ,Obesity ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Oral and gastrointestinal ,Clinical sciences - Abstract
The accumulation of excess fat in the liver (hepatic steatosis) in the absence of heavy alcohol consumption causes nonalcoholic fatty liver disease (NAFLD), which has become a global epidemic. Identifying metabolic risk factors that interact with the genetic risk of NAFLD is important for reducing disease burden. We tested whether serum glucose, insulin, insulin resistance, triglyceride (TG), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, body mass index (BMI), and waist-to-hip ratio adjusted for BMI interact with genetic variants in or near the patatin-like phospholipase domain containing 3 (PNPLA3) gene, the glucokinase regulatory protein (GCKR) gene, the neurocan/transmembrane 6 superfamily member 2 (NCAN/TM6SF2) gene, and the lysophospholipase-like 1 (LYPLAL1) gene to exacerbate hepatic steatosis, estimated by liver attenuation. We performed association analyses in 10 population-based cohorts separately and then meta-analyzed results in up to 14,751 individuals (11,870 of European ancestry and 2,881 of African ancestry). We found that PNPLA3-rs738409 significantly interacted with insulin, insulin resistance, BMI, glucose, and TG to increase hepatic steatosis in nondiabetic individuals carrying the G allele. Additionally, GCKR-rs780094 significantly interacted with insulin, insulin resistance, and TG. Conditional analyses using the two largest European ancestry cohorts in the study showed that insulin levels accounted for most of the interaction of PNPLA3-rs738409 with BMI, glucose, and TG in nondiabetic individuals. Insulin, PNPLA3-rs738409, and their interaction accounted for at least 8% of the variance in hepatic steatosis in these two cohorts. Conclusion: Insulin resistance, either directly or through the resultant elevated insulin levels, more than other metabolic traits, appears to amplify the PNPLA3-rs738409-G genetic risk for hepatic steatosis. Improving insulin resistance in nondiabetic individuals carrying PNPLA3-rs738409-G may preferentially decrease hepatic steatosis.
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- 2019
31. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
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de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, and Giulianini, Franco
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Epidemiology ,Health Sciences ,Substance Misuse ,Alcoholism ,Alcohol Use and Health ,Human Genome ,Prevention ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Cardiovascular ,Adolescent ,Adult ,Aged ,Alcohol Drinking ,Cholesterol ,HDL ,Cholesterol ,LDL ,Female ,Genome-Wide Association Study ,Genotype ,Humans ,Life Style ,Lipids ,Male ,Middle Aged ,Phenotype ,Racial Groups ,Triglycerides ,Vascular Endothelial Growth Factor B ,Young Adult ,alcohol consumption ,cholesterol ,gene-environment interactions ,gene-lifestyle interactions ,genome-wide association studies ,lipids ,triglycerides ,InterAct Consortium ,Lifelines Cohort ,Groningen ,The Netherlands ,Mathematical Sciences ,Medical and Health Sciences - Abstract
A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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- 2019
32. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
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Justice, Anne E, Karaderi, Tugce, Highland, Heather M, Young, Kristin L, Graff, Mariaelisa, Lu, Yingchang, Turcot, Valérie, Auer, Paul L, Fine, Rebecca S, Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W, Locke, Adam E, Medina-Gomez, Carolina, Esko, Tõnu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie CY, Heard-Costa, Nancy L, Feitosa, Mary F, Manning, Alisa K, Willems, Sara M, Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S, Allison, Matthew, Amouyel, Philippe, Arzumanyan, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Caulfield, Mark J, Cesana, Giancarlo, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Collins, Francis S, Cook, James P, Cox, Amanda J, Crosslin, David S, Danesh, John, de Bakker, Paul IW, Denus, Simon de, Mutsert, Renée de, Dedoussis, George, Demerath, Ellen W, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Dörr, Marcus, Drenos, Fotios, Dubé, Marie-Pierre, Dunning, Alison M, Easton, Douglas F, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C, Fornage, Myriam, Fox, Caroline S, Franks, Paul W, Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Grove, Megan L, Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, and Hattersley, Andrew T
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Clinical Research ,Obesity ,Genetics ,Nutrition ,Prevention ,Biotechnology ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Cardiovascular ,Animals ,Body Fat Distribution ,Body Mass Index ,Case-Control Studies ,Drosophila ,Exome ,Female ,Gene Frequency ,Genetic Predisposition to Disease ,Genetic Variation ,Genome-Wide Association Study ,Homeostasis ,Humans ,Lipids ,Male ,Proteins ,Risk Factors ,Waist-Hip Ratio ,CHD Exome+ Consortium ,Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium ,EPIC-CVD Consortium ,ExomeBP Consortium ,Global Lipids Genetic Consortium ,GoT2D Genes Consortium ,InterAct ,ReproGen Consortium ,T2D-Genes Consortium ,MAGIC Investigators ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF
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- 2019
33. Disentangling the genetics of lean mass.
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Karasik, David, Zillikens, M, Hsu, Yi-Hsiang, Aghdassi, Ali, Akesson, Kristina, Amin, Najaf, Barroso, Inês, Bennett, David, Bertram, Lars, Bochud, Murielle, Borecki, Ingrid, Broer, Linda, Buchman, Aron, Byberg, Liisa, Campbell, Harry, Campos-Obando, Natalia, Cauley, Jane, Cawthon, Peggy, Chambers, John, Chen, Zhao, Cho, Nam, Choi, Hyung, Chou, Wen-Chi, Cummings, Steven, de Groot, Lisette, De Jager, Phillip, Demuth, Ilja, Diatchenko, Luda, Econs, Michael, Eiriksdottir, Gudny, Enneman, Anke, Eriksson, Joel, Eriksson, Johan, Estrada, Karol, Evans, Daniel, Feitosa, Mary, Fu, Mao, Gieger, Christian, Grallert, Harald, Gudnason, Vilmundur, Lenore, Launer, Hayward, Caroline, Hofman, Albert, Homuth, Georg, Huffman, Kim, Husted, Lise, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Johnson, Toby, Biffar, Reiner, Jordan, Joanne, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas, Klopp, Norman, Kloth, Jacqueline, Koller, Daniel, Kooner, Jaspal, Kraus, William, Kritchevsky, Stephen, Kutalik, Zoltán, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Langdahl, Bente, Lerch, Markus, Lewis, Joshua, Lill, Christina, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Livshits, Gregory, Ljunggren, Östen, Loos, Ruth, Lorentzon, Mattias, Luan, Jianan, Luben, Robert, Malkin, Ida, McGuigan, Fiona, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Michaëlsson, Karl, Mitchell, Braxton, Morris, Andrew, Mosekilde, Leif, Nethander, Maria, Newman, Anne, OConnell, Jeffery, Oostra, Ben, Orwoll, Eric, Palotie, Aarno, Peacock, Munro, Perola, Markus, and Peters, Annette
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ADAMTS Proteins ,Absorptiometry ,Photon ,Adipose Tissue ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Body Composition ,Body Fluid Compartments ,Electric Impedance ,Extracellular Matrix Proteins ,Female ,Genome-Wide Association Study ,Humans ,Male ,Middle Aged ,Muscle ,Skeletal ,Phenotype ,Polymorphism ,Single Nucleotide ,RNA-Binding Proteins ,Receptor ,Melanocortin ,Type 4 ,Versicans ,White People ,Young Adult - Abstract
BACKGROUND: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. OBJECTIVES: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. METHODS: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). RESULTS: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as sumo wrestler loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed body builder loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in body builder loci were associated with metabolic protection. CONCLUSIONS: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
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- 2019
34. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.
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Kilpeläinen, Tuomas O, Bentley, Amy R, Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W, Jakupović, Hermina, Chasman, Daniel I, Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R, de Las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F, Kho, Minjung, Musani, Solomon K, Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Li, Changwei, Lohman, Kurt K, Marten, Jonathan, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Zhao, Jing Hua, Kraja, Aldi T, Kühnel, Brigitte, Laguzzi, Federica, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M, Takeuchi, Fumihiko, van der Most, Peter J, Varga, Tibor V, Verweij, Niek, Ware, Erin B, Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R, Amin, Najaf, Arnett, Donna K, Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickaël, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renée, de Silva, H Janaka, de Vries, Paul S, Demirkan, Ayşe, Ding, Jingzhong, Eaton, Charles B, Faul, Jessica D, Friedlander, Yechiel, Gabriel, Kelley P, Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C, Ikram, M Arfan, Jonas, Jost B, Koh, Woon-Puay, Komulainen, Pirjo, and Krieger, Jose E
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Lifelines Cohort Study ,Humans ,Cholesterol ,Lipids ,Triglycerides ,Calcium-Binding Proteins ,Muscle Proteins ,Microtubule-Associated Proteins ,Membrane Proteins ,Nerve Tissue Proteins ,Transcription Factors ,Exercise ,Genotype ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,African Continental Ancestry Group ,Asian Continental Ancestry Group ,European Continental Ancestry Group ,Hispanic Americans ,Brazil ,Female ,Male ,Lipid Metabolism ,Cholesterol ,LDL ,Cholesterol ,HDL ,Genome-Wide Association Study ,Young Adult ,Genetic Loci ,LIM-Homeodomain Proteins ,and over ,HDL ,LDL - Abstract
Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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- 2019
35. Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- Author
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Gorski, Mathias, Rasheed, Humaira, Teumer, Alexander, Thomas, Laurent F., Graham, Sarah E., Sveinbjornsson, Gardar, Winkler, Thomas W., Günther, Felix, Stark, Klaus J., Chai, Jin-Fang, Tayo, Bamidele O., Wuttke, Matthias, Li, Yong, Tin, Adrienne, Ahluwalia, Tarunveer S., Ärnlöv, Johan, Åsvold, Bjørn Olav, Bakker, Stephan J.L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Biino, Ginevra, Böhnke, Michael, Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Brumpton, Ben, Carroll, Robert J., Chaker, Layal, Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Chu, Audrey Y., Ciullo, Marina, Cocca, Massimiliano, Cook, James P., Coresh, Josef, Cusi, Daniele, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Evans, Michele K., Feitosa, Mary F., Franke, Andre, Freitag-Wolf, Sandra, Fuchsberger, Christian, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Gieger, Christian, Gudbjartsson, Daniel F., Hallan, Stein, Hamet, Pavel, Hishida, Asahi, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Holm, Hilma, Hoppmann, Anselm, Horn, Katrin, Hutri-Kähönen, Nina, Hveem, Kristian, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Karabegović, Irma, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Kuusisto, Johanna, Laakso, Markku, Lange, Leslie A., Lehtimäki, Terho, Li, Man, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M., Loos, Ruth J.F., Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Matias-Garcia, Pamela R., Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Morris, Andrew P., Mychaleckyj, Josyf C., Nadkarni, Girish N., Naito, Mariko, Nakatochi, Masahiro, Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., Nutile, Teresa, O’Donoghue, Michelle L., O'Connell, Jeffrey, Olafsson, Isleifur, Orho-Melander, Marju, Parsa, Afshin, Pendergrass, Sarah A., Penninx, Brenda W.J.H., Pirastu, Mario, Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rheinberger, Myriam, Rice, Kenneth M., Rizzi, Federica, Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Ruggiero, Daniela, Ryan, Kathleen A., Sabanayagam, Charumathi, Salvi, Erika, Schmidt, Helena, Schmidt, Reinhold, Scholz, Markus, Schöttker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Sieber, Karsten B., Sim, Xueling, Sims, Mario, Snieder, Harold, Stanzick, Kira J., Thorsteinsdottir, Unnur, Stocker, Hannah, Strauch, Konstantin, Stringham, Heather M., Sulem, Patrick, Szymczak, Silke, Taylor, Kent D., Thio, Chris H.L., Tremblay, Johanne, Vaccargiu, Simona, van der Harst, Pim, van der Most, Peter J., Verweij, Niek, Völker, Uwe, Wakai, Kenji, Waldenberger, Melanie, Wallentin, Lars, Wallner, Stefan, Wang, Judy, Waterworth, Dawn M., White, Harvey D., Willer, Cristen J., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yerges-Armstrong, Laura M., Zimmermann, Martina, Zonderman, Alan B., Bergler, Tobias, Stefansson, Kari, Böger, Carsten A., Pattaro, Cristian, Köttgen, Anna, Kronenberg, Florian, and Heid, Iris M.
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- 2022
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36. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
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Ramdas, Shweta, Judd, Jonathan, Graham, Sarah E., Kanoni, Stavroula, Wang, Yuxuan, Surakka, Ida, Wenz, Brandon, Clarke, Shoa L., Chesi, Alessandra, Wells, Andrew, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J.M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Lee, Wen-Jane, Hsiung, Chao Agnes, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Schönherr, Sebastian, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Le, Phuong, Feitosa, Mary F., Wojczynski, Mary K., Hemerich, Daiane, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Noah, Tsao L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Emmel, Carina, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Sankareswaran, Alagu, Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R.H.J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Morgan, Anna, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R.B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, He, Karen Y., Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H.H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W.J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Ida Chen, Yii-Der, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D.C., Arnett, Donna K., Walker, Mark, Scott, Laura J., Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N.A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Lu, Fan, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, t Hart, Leen M., Elders, Petra J.M., Rader, Daniel J., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J.F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F.A., Kiemeney, Lambertus, de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., Willems van Dijk, Ko, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Huey-Herng Sheu, Wayne, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K.E., Boomsma, Dorret I., de Geus, Eco J.C., Cupples, L. Adrienne, van Meurs, Joyce B.J., Ikram, Arfan, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Tuomilehto, Jaakko, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, Y. Eugene, Ho, Yuk-Lam, Lynch, Julie A., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Struan Grant, Natarajan, Pradeep, Sun, Yan V., Morris, Andrew P., Deloukas, Panos, Peloso, Gina, Assimes, Themistocles L., Willer, Cristen J., Zhu, Xiang, and Brown, Christopher D.
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- 2022
- Full Text
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37. Distribution of 54 polygenic risk scores for common diseases in long lived individuals and their offspring
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Gunn, Sophia, Wainberg, Michael, Song, Zeyuan, Andersen, Stacy, Boudreau, Robert, Feitosa, Mary F., Tan, Qihua, Montasser, May E., O’Connell, Jeffrey R., Stitziel, Nathan, Price, Nathan, Perls, Thomas, Schork, Nicholas J., and Sebastiani, Paola
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- 2022
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38. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
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Winkler, Thomas W., Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X., Stanzick, Kira J., Thomas, Laurent F., Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y., Tayo, Bamidele, Thio, Chris H. L., Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B., Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J., Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P. J., Zonderman, Alan B., Smith, Albert V., Oldehinkel, Albertine J., De Grandi, Alessandro, Rosenkranz, Alexander R., Franke, Andre, Teren, Andrej, Metspalu, Andres, Hicks, Andrew A., Morris, Andrew P., Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I., Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I., Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K., Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H., Ning, Boting, Penninx, Brenda W. J. H., Vanderwerff, Brett R., Psaty, Bruce M., Kammerer, Candace M., Langefeld, Carl D., Hayward, Caroline, Spracklen, Cassandra N., Robinson-Cohen, Cassianne, Hartman, Catharina A., Lindgren, Cecilia M., Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M., Schulz, Christina-Alexandra, Willer, Cristen J., Chasman, Daniel I., Gudbjartsson, Daniel F., Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J., Waterworth, Dawn M., Mascalzoni, Deborah, Mook-Kanamori, Dennis O., Reilly, Dermot F., Daw, E. Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N., Delgado, Graciela E., Montgomery, Grant W., Snieder, Harold, Campbell, Harry, White, Harvey D., Gao, He, Stringham, Heather M., Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holgen, Kramer, Holly, Rudan, Igor, Nolte, Ilja M., Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P., Wilson, James F., Halbritter, Jan, Felix, Janine F., Divers, Jasmin, Kooner, Jaspal S., Lee, Jeannette Jen-Mai, O’Connell, Jeffrey, Rotter, Jerome I., Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C., Whitfield, John B., Gaziano, John M., Marten, Jonathan, Coresh, Josef, Jonas, Jost B., Mychaleckyj, Josyf C., Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L., Endlich, Karlhans, Dittrich, Katalin, Ryan, Kathleen A., Rice, Kenneth M., Taylor, Kent D., Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lars, Wallentin, Lars, Yerges-Armstrong, Laura M., Raffield, Laura M., Phillips, Lawrence S., Launer, Lenore J., Lyytikäinen, Leo-Pekka, Lange, Leslie A., Citterio, Lorena, Klaric, Lucija, Ikram, M. Arfan, Ising, Marcus, Kleber, Marcus E., Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Markus, Perola, Markus, de Borst, Martin H., Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F., Biggs, Mary L., Wojczynski, Mary K., Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthias, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H., Stumvoll, Michael, Province, Michael A., Evans, Michele K., O’Donoghue, Michelle L., Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A., Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G., Tan, Nicholas Y. Q., Palmer, Nicholette D., Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T., Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P., Sulem, Patrick, Magnusson, Patrik K. E., Elliott, Paul, Ridker, Paul M., Hamet, Pavel, Svensson, Per O., Joshi, Peter K., Kovacs, Peter, Pramstaller, Peter P., Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z. H., Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M., Carroll, Robert J., Gansevoort, Ron T., Loos, Ruth J. F., Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A., Graham, Sarah E., Gordon, Scott D., Hwang, Shih-Jen, Kerr, Shona M., Vaccargiu, Simona, Patil, Snehal B., Hallan, Stein, Bakker, Stephan J. L., Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S., Lehtimäki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tõnu, Haller, Toomas, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmantas, Gudnason, Vilmundur, Jaddoe, Vincent W. V., Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Stark, Klaus J., Stefansson, Kari, Böger, Carsten A., Hung, Adriana M., Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, and Heid, Iris M.
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- 2022
- Full Text
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39. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
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Kanoni, Stavroula, Graham, Sarah E., Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L., Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J. M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Yousri, Noha A., Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Hwu, Chii-Min, Hung, Yi-Jen, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, EWarwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Vazquez-Moreno, Miguel, Feitosa, Mary F., Wojczynski, Mary K., Wang, Zhe, Preuss, Michael H., Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Tsao, Noah L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Frank, Mirjam, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Bayyana, Swati, Stringham, Heather M., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Nardone, Giuseppe Giovanni, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R. B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Liang, Jingjing, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, Hollander, Anneke Iden, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Costanzo, Maria C., Jang, Dongkeun, Burtt, Noël P., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, EShyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M.‘t, Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Chuang, Lee-Ming, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., Willemsen, Allegonda H. M., Cupples, LAdrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, YEugene, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter W. F., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Mohlke, Karen L., Sun, Yan V., Morris, Andrew P., Boehnke, Michael, Brown, Christopher D., Natarajan, Pradeep, Deloukas, Panos, Willer, Cristen J., Assimes, Themistocles L., and Peloso, Gina M.
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- 2022
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40. Discovery of genomic and transcriptomic pleiotropy between kidney function and soluble receptor for advanced glycation end products using correlated meta‐analyses: The Long Life Family Study.
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Feitosa, Mary F., Lin, Shiow J., Acharya, Sandeep, Thyagarajan, Bharat, Wojczynski, Mary K., Kuipers, Allison L., Kulminski, Alexander, Christensen, Kaare, Zmuda, Joseph M., Brent, Michael R., and Province, Michael A.
- Subjects
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ADVANCED glycation end-products , *KIDNEY tubules , *CHRONIC kidney failure , *CYSTATIN C , *GENE expression - Abstract
Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end‐products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole‐genome sequencing and correlated meta‐analyses on combined genome‐wide association study (GWAS) p‐values in 4182 individuals (age range: 24–110) from the Long Life Family Study (LLFS). We also conducted transcriptome‐wide association studies (TWAS) on whole blood in a subset of 1209 individuals. We identified 59 pleiotropic GWAS loci (p < 5 × 10−8) and 17 TWAS genes (Bonferroni‐p < 2.73 × 10−6) for eGFR traits and sRAGE. TWAS genes, LSP1 and MIR23AHG, were associated with eGFR and sRAGE located within GWAS loci, lncRNA‐KCNQ1OT1 and CACNA1A/CCDC130, respectively. GWAS variants were eQTLs in the kidney glomeruli and tubules, and GWAS genes predicted kidney carcinoma. TWAS genes harbored eQTLs in the kidney, predicted kidney carcinoma, and connected enhancer‐promoter variants with kidney function‐related phenotypes at p < 5 × 10−8. Additionally, higher allele frequencies of protective variants for eGFR traits were detected in LLFS than in ALFA‐Europeans and TOPMed, suggesting better kidney function in healthy‐aging LLFS than in general populations. Integrating genomic annotation and transcriptional gene activity revealed the enrichment of genetic elements in kidney function and aging‐related processes. The identified pleiotropic loci and gene expressions for eGFR and sRAGE suggest their underlying shared genetic effects and highlight their roles in kidney‐ and aging‐related signaling pathways. [ABSTRACT FROM AUTHOR]
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- 2024
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41. The power of genetic diversity in genome-wide association studies of lipids
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Graham, Sarah E., Clarke, Shoa L., Wu, Kuan-Han H., Kanoni, Stavroula, Zajac, Greg J. M., Ramdas, Shweta, Surakka, Ida, Ntalla, Ioanna, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Hwang, Mi Yeong, Han, Sohee, Narita, Akira, Choudhury, Ananyo, Bentley, Amy R., Ekoru, Kenneth, Verma, Anurag, Trivedi, Bhavi, Martin, Hilary C., Hunt, Karen A., Hui, Qin, Klarin, Derek, Zhu, Xiang, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Ruotsalainen, Sanni E., Havulinna, Aki S., Veturi, Yogasudha, Feng, QiPing, Rosenthal, Elisabeth A., Lingren, Todd, Pacheco, Jennifer Allen, Pendergrass, Sarah A., Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Hindy, George, Rasheed, Asif, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Willemsen, Gonneke, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Yao, Jie, Manichaikul, Ani, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Sidore, Carlo, Fiorillo, Edoardo, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Thuesen, Betina H., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Feitosa, Mary F., Wojczynski, Mary K., Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Kember, Rachel L., Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L., Marten, Jonathan, Schmidt, Börge, Arendt, Marina, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U., Yousri, Noha A., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Chai, Xiaoran, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Hung, Yi-Jen, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Gorski, Mathias, Brumat, Marco, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Xue, Chao, Zhang, Jifeng, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., Lee, Jiwon, van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Zimmermann, Martina E., Lee, Jong Young, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hildalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Schwander, Karen, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Highland, Heather M., Young, Kristin L., Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Nadkarni, Girish N., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, Konain Fatima, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Chen, Y. Eugene, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Jung, Bettina, Böger, Carsten A., Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Yajnik, Chittaranjan S., Mercader, Josep M., Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Lu, Fan, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Parra, Esteban J., Cruz, Miguel, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, ’t Hart, Leen M., Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Cucca, Francesco, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., de Geus, Eco J. C., Cupples, L. Adrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Justice, Anne E., Baras, Aris, Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Thorsteinsdottir, Unnur, Stefansson, Kari, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Rotimi, Charles N., Hazelhurst, Scott, Ramsay, Michèle, Trembath, Richard C., van Heel, David A., Tamiya, Gen, Yamamoto, Masayuki, Kim, Bong-Jo, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Natarajan, Pradeep, Peloso, Gina M., Brown, Christopher D., Morris, Andrew P., Assimes, Themistocles L., Deloukas, Panos, Sun, Yan V., and Willer, Cristen J.
- Published
- 2021
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42. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
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Ligthart, Symen, Vaez, Ahmad, Võsa, Urmo, Stathopoulou, Maria G, de Vries, Paul S, Prins, Bram P, Van der Most, Peter J, Tanaka, Toshiko, Naderi, Elnaz, Rose, Lynda M, Wu, Ying, Karlsson, Robert, Barbalic, Maja, Lin, Honghuang, Pool, René, Zhu, Gu, Macé, Aurélien, Sidore, Carlo, Trompet, Stella, Mangino, Massimo, Sabater-Lleal, Maria, Kemp, John P, Abbasi, Ali, Kacprowski, Tim, Verweij, Niek, Smith, Albert V, Huang, Tao, Marzi, Carola, Feitosa, Mary F, Lohman, Kurt K, Kleber, Marcus E, Milaneschi, Yuri, Mueller, Christian, Huq, Mahmudul, Vlachopoulou, Efthymia, Lyytikäinen, Leo-Pekka, Oldmeadow, Christopher, Deelen, Joris, Perola, Markus, Zhao, Jing Hua, Feenstra, Bjarke, Amini, Marzyeh, Lahti, Jari, Schraut, Katharina E, Fornage, Myriam, Suktitipat, Bhoom, Chen, Wei-Min, Li, Xiaohui, Nutile, Teresa, Malerba, Giovanni, Luan, Jian’an, Bak, Tom, Schork, Nicholas, Del Greco M., Fabiola, Thiering, Elisabeth, Mahajan, Anubha, Marioni, Riccardo E, Mihailov, Evelin, Eriksson, Johan, Ozel, Ayse Bilge, Zhang, Weihua, Nethander, Maria, Cheng, Yu-Ching, Aslibekyan, Stella, Ang, Wei, Gandin, Ilaria, Yengo, Loïc, Portas, Laura, Kooperberg, Charles, Hofer, Edith, Rajan, Kumar B, Schurmann, Claudia, Hollander, Wouter den, Ahluwalia, Tarunveer Singh, Zhao, Jing, Draisma, Harmen HM, Ford, Ian, Timpson, Nicholas, Teumer, Alexander, Huang, Hongyan, Wahl, Simone, Liu, YongMei, Huang, Jie, Uh, Hae-Won, Geller, Frank, Joshi, Peter K, Yanek, Lisa R, Trabetti, Elisabetta, Lehne, Benjamin, Vozzi, Diego, Verbanck, Marie, Biino, Ginevra, Saba, Yasaman, Meulenbelt, Ingrid, O’Connell, Jeff R, Laakso, Markku, Giulianini, Franco, Magnusson, Patrik KE, Ballantyne, Christie M, and Hottenga, Jouke Jan
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Biomarkers ,Bipolar Disorder ,Body Mass Index ,C-Reactive Protein ,Child ,Female ,Genetic Loci ,Genome-Wide Association Study ,Humans ,Inflammation ,Liver ,Male ,Mendelian Randomization Analysis ,Metabolic Networks and Pathways ,Middle Aged ,Schizophrenia ,Young Adult ,LifeLines Cohort Study ,CHARGE Inflammation Working Group ,C-reactive protein ,DEPICT ,Mendelian randomization ,coronary artery disease ,genome-wide association study ,inflammation ,inflammatory disorders ,schizophrenia ,system biology ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.
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- 2018
43. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.
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Wyss, Annah B, Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N, Lahousse, Lies, Latourelle, Jeanne C, Smith, Albert Vernon, Bartz, Traci M, Feitosa, Mary F, Gao, Wei, Ahluwalia, Tarunveer S, Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K, Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E, Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D, Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M, Hu, Donglei, Mogil, Lauren S, Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B, Kalhan, Ravi, Heckbert, Susan R, Paternoster, Lavinia, Burkart, Kristin M, Liu, Yongmei, Holliday, Elizabeth G, Wilson, James G, Vonk, Judith M, Sanders, Jason L, Barr, R Graham, de Mutsert, Renée, Menezes, Ana Maria Baptista, Adams, Hieab HH, van den Berge, Maarten, Joehanes, Roby, Levin, Albert M, Liberto, Jennifer, Launer, Lenore J, Morrison, Alanna C, Sitlani, Colleen M, Celedón, Juan C, Kritchevsky, Stephen B, Scott, Rodney J, Christensen, Kaare, Rotter, Jerome I, Bonten, Tobias N, Wehrmeister, Fernando César, Bossé, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A, Kaplan, Robert C, Lohman, Kurt, McEvoy, Mark, Province, Michael A, Rosendaal, Frits R, Taylor, Kent D, Nickle, David C, Williams, L Keoki, Burchard, Esteban G, Wheeler, Heather E, Sin, Don D, Gudnason, Vilmundur, North, Kari E, Fornage, Myriam, Psaty, Bruce M, Myers, Richard H, O'Connor, George, Hansen, Torben, Laurie, Cathy C, Cassano, Patricia A, Sung, Joohon, Kim, Woo Jin, Attia, John R, Lange, Leslie, Boezen, H Marike, Thyagarajan, Bharat, Rich, Stephen S, Mook-Kanamori, Dennis O, Horta, Bernardo Lessa, Uitterlinden, André G, Im, Hae Kyung, Cho, Michael H, Brusselle, Guy G, and Gharib, Sina A
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Lung ,Humans ,Lung Diseases ,Pulmonary Disease ,Chronic Obstructive ,Genetic Predisposition to Disease ,Vital Capacity ,Forced Expiratory Volume ,Regression Analysis ,Sample Size ,Smoking ,Genomics ,Linkage Disequilibrium ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,African Continental Ancestry Group ,Asian Americans ,European Continental Ancestry Group ,Hispanic Americans ,Female ,Male ,Genome-Wide Association Study ,Polymorphism ,Single Nucleotide ,Pulmonary Disease ,Chronic Obstructive - Abstract
Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.
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- 2018
44. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.
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Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas GD, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie CY, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Gonçalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der I, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul IW, Groot, Mark CH, Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, Heijer, Martin, Hollander, Anneke I, Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, and Easton, Douglas F
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CHD Exome+ Consortium ,EPIC-CVD Consortium ,ExomeBP Consortium ,Global Lipids Genetic Consortium ,GoT2D Genes Consortium ,EPIC InterAct Consortium ,INTERVAL Study ,ReproGen Consortium ,T2D-Genes Consortium ,MAGIC Investigators ,Understanding Society Scientific Group ,Nutrition ,Obesity ,Developmental Biology ,Medical and Health Sciences ,Biological Sciences - Abstract
In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.
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- 2018
45. Genome‐Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent
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Smith, Caren E, Follis, Jack L, Dashti, Hassan S, Tanaka, Toshiko, Graff, Mariaelisa, Fretts, Amanda M, Kilpeläinen, Tuomas O, Wojczynski, Mary K, Richardson, Kris, Nalls, Mike A, Schulz, Christina‐Alexandra, Liu, Yongmei, Frazier‐Wood, Alexis C, van Eekelen, Esther, Wang, Carol, de Vries, Paul S, Mikkilä, Vera, Rohde, Rebecca, Psaty, Bruce M, Hansen, Torben, Feitosa, Mary F, Lai, Chao‐Qiang, Houston, Denise K, Ferruci, Luigi, Ericson, Ulrika, Wang, Zhe, de Mutsert, Renée, Oddy, Wendy H, de Jonge, Ester AL, Seppälä, Ilkka, Justice, Anne E, Lemaitre, Rozenn N, Sørensen, Thorkild IA, Province, Michael A, Parnell, Laurence D, Garcia, Melissa E, Bandinelli, Stefania, Orho‐Melander, Marju, Rich, Stephen S, Rosendaal, Frits R, Pennell, Craig E, Jong, Jessica C Kiefte‐de, Kähönen, Mika, Young, Kristin L, Pedersen, Oluf, Aslibekyan, Stella, Rotter, Jerome I, Mook‐Kanamori, Dennis O, Zillikens, M Carola, Raitakari, Olli T, North, Kari E, Overvad, Kim, Arnett, Donna K, Hofman, Albert, Lehtimäki, Terho, Tjønneland, Anne, Uitterlinden, André G, Rivadeneira, Fernando, Franco, Oscar H, German, J Bruce, Siscovick, David S, Cupples, L Adrienne, and Ordovás, José M
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Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Genetics ,Prevention ,Nutrition ,Obesity ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Cancer ,Metabolic and endocrine ,Actins ,Adult ,Aged ,Body Mass Index ,Cohort Studies ,Cross-Sectional Studies ,Dairy Products ,Female ,Gene Frequency ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Middle Aged ,Myosin-Light-Chain Phosphatase ,Polymorphism ,Single Nucleotide ,White People ,body mass index ,CHARGE consortium ,dairy intake ,genome-wide interaction study ,meta-analysis ,Food Sciences ,Public Health and Health Services ,Food Science ,Nutrition & Dietetics ,Food sciences ,Nutrition and dietetics - Abstract
ScopeBody weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.Methods and resultsA genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction
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- 2018
46. Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization Analysis of 184802 Individuals from 25 Studies
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Huang, Tao, Ding, Ming, Bergholdt Helle, KM, Wang, Tiange, Heianza, Yoriko, Sun, Dianjianyi, Frazier-Wood Alexis, C, Aslibekyan, Stella, North Kari, E, Voortman, Trudy, Graff, Mariaelisa, Smith Caren, E, Lai, Chao-Qiang, Varbo, Anette, Lemaitre, Rozenn N, de Jonge, M Ester AL, Fumeron, Frédéric, Corella, Dolores, Wang, Carol A, Tjønneland, Anne, Overvad, Kim, Sørensen, Thorkild IA, Feitosa, Mary F, Wojczynski, Mary K, Kähönen, Mika, Renström, Frida, Psaty, Bruce M, Siscovick, David S, Barroso, Inês, Johansson, Ingegerd, Hernandez, Dena, Ferrucci, Luigi, Bandinelli, Stefania, Linneberg, Allan, Zillikens, M Carola, Sandholt, Camilla Helene, Pedersen, Oluf, Hansen, Torben, Schulz, Christina-Alexandra, Sonestedt, Emily, Orho-Melander, Marju, Chen, Tzu-An, Rotter, Jerome I, Allison, Mathew A, Rich, Stephen S, Sorlí, Jose V, Coltell, Oscar, Pennell, Craig E, Eastwood, Peter, Hofman, Albert, Uitterlinden, Andre G, van Rooij, Frank JA, Chu, Audrey Y, Rose, Lynda M, Ridker, Paul M, Viikari, Jorma, Raitakari, Olli, Lehtimäki, Terho, Mikkilä, Vera, Willett, Walter C, Wang, Yujie, Tucker, Katherine L, Ordovas, Jose M, Kilpeläinen, Tuomas O, Province, Michael A, Franks, Paul W, Arnett, Donna K, Tanaka, Toshiko, Toft, Ulla, Ericson, Ulrika, Franco, Oscar H, Mozaffarian, Dariush, Hu, Frank B, Chasman, Daniel I, Nordestgaard, Børge G, Ellervik, Christina, and Qi, Lu
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Biomedical and Clinical Sciences ,Nutrition and Dietetics ,Prevention ,Genetics ,Adult ,Body Mass Index ,Body Weight ,Cross-Sectional Studies ,Dairy Products ,Genotype ,Humans ,Mendelian Randomization Analysis ,Polymorphism ,Genetic ,Polymorphism ,Single Nucleotide ,Prospective Studies ,Mendelian Randomization of Dairy Consumption Working Group ,Medical Biotechnology ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,General Clinical Medicine ,Clinical sciences ,Medical biochemistry and metabolomics - Abstract
BackgroundAssociations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.MethodsWe performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.ResultsHigher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00-0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14-0.25) serving/day higher dairy intake (P = 3.15 × 10-12) and 0.12 (95% CI, 0.06-0.17) kg/m2 higher BMI (P = 2.11 × 10-5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27-0.92; P = 3.0 × 10-4).ConclusionsThe present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.
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- 2018
47. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
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Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M, Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Vitart, Veronique, Wang, Yajuan, Ware, Erin B, Warren, Helen R, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L, Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Ida Chen, Yii-Der, Connell, John M, Correa, Adolfo, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B, and Ehret, Georg
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InterAct Consortium ,Humans ,Hypertension ,Genetic Predisposition to Disease ,Cohort Studies ,Pedigree ,Alcohol Drinking ,Blood Pressure ,Polymorphism ,Single Nucleotide ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Continental Population Groups ,Female ,Male ,Genome-Wide Association Study ,Young Adult ,Gene-Environment Interaction ,General Science & Technology - Abstract
Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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- 2018
48. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- Author
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Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas GD, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie CY, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Gonçalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der I, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D’Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul IW, Groot, Mark CH, Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, Heijer, Martin, Hollander, Anneke I, Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, and Easton, Douglas F
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Genetics ,Biotechnology ,Nutrition ,Obesity ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Cancer ,Stroke ,Metabolic and endocrine ,Cardiovascular ,Oral and gastrointestinal ,Adult ,Animals ,Body Mass Index ,Drosophila ,Energy Intake ,Energy Metabolism ,Female ,Gene Frequency ,Genetic Variation ,Humans ,Male ,Proteins ,Syndrome ,CHD Exome+ Consortium ,EPIC-CVD Consortium ,ExomeBP Consortium ,Global Lipids Genetic Consortium ,GoT2D Genes Consortium ,EPIC InterAct Consortium ,INTERVAL Study ,ReproGen Consortium ,T2D-Genes Consortium ,MAGIC Investigators ,Understanding Society Scientific Group ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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- 2018
49. End of Life Events and Causes of Death in Danish Long-Lived Siblings: Reduced Dementia Risk Compared to Sporadic Long-Livers
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Galvin, Angéline, primary, Pedersen, Jacob Krabbe, additional, Arbeev, Konstantin G., additional, Feitosa, Mary F., additional, Ukraintseva, Svetlana, additional, Yao, Shanshan, additional, Newman, Anne B., additional, and Christensen, Kaare, additional
- Published
- 2024
- Full Text
- View/download PDF
50. Genome-Wide Epistatic Network Analyses of Semantic Fluency in Older Adults
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Tan, Qihua, primary, Li, Weilong, additional, Nygaard, Marianne, additional, An, Ping, additional, Feitosa, Mary, additional, Wojczynski, Mary K., additional, Zmuda, Joseph, additional, Arbeev, Konstantin, additional, Ukraintseva, Svetlana, additional, Yashin, Anatoliy, additional, Christensen, Kaare, additional, and Mengel-From, Jonas, additional
- Published
- 2024
- Full Text
- View/download PDF
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