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2. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Author

McCartney, Daniel L, Min, Josine L, Richmond, Rebecca C, Lu, Ake T, Sobczyk, Maria K, Davies, Gail, Broer, Linda, Guo, Xiuqing, Jeong, Ayoung, Jung, Jeesun, Kasela, Silva, Katrinli, Seyma, Kuo, Pei-Lun, Matias-Garcia, Pamela R, Mishra, Pashupati P, Nygaard, Marianne, Palviainen, Teemu, Patki, Amit, Raffield, Laura M, Ratliff, Scott M, Richardson, Tom G, Robinson, Oliver, Soerensen, Mette, Sun, Dianjianyi, Tsai, Pei-Chien, van der Zee, Matthijs D, Walker, Rosie M, Wang, Xiaochuan, Wang, Yunzhang, Xia, Rui, Xu, Zongli, Yao, Jie, Zhao, Wei, Correa, Adolfo, Boerwinkle, Eric, Dugué, Pierre-Antoine, Durda, Peter, Elliott, Hannah R, Gieger, Christian, de Geus, Eco JC, Harris, Sarah E, Hemani, Gibran, Imboden, Medea, Kähönen, Mika, Kardia, Sharon LR, Kresovich, Jacob K, Li, Shengxu, Lunetta, Kathryn L, Mangino, Massimo, Mason, Dan, McIntosh, Andrew M, Mengel-From, Jonas, Moore, Ann Zenobia, Murabito, Joanne M, Ollikainen, Miina, Pankow, James S, Pedersen, Nancy L, Peters, Annette, Polidoro, Silvia, Porteous, David J, Raitakari, Olli, Rich, Stephen S, Sandler, Dale P, Sillanpää, Elina, Smith, Alicia K, Southey, Melissa C, Strauch, Konstantin, Tiwari, Hemant, Tanaka, Toshiko, Tillin, Therese, Uitterlinden, Andre G, Van Den Berg, David J, van Dongen, Jenny, Wilson, James G, Wright, John, Yet, Idil, Arnett, Donna, Bandinelli, Stefania, Bell, Jordana T, Binder, Alexandra M, Boomsma, Dorret I, Chen, Wei, Christensen, Kaare, Conneely, Karen N, Elliott, Paul, Ferrucci, Luigi, Fornage, Myriam, Hägg, Sara, Hayward, Caroline, Irvin, Marguerite, Kaprio, Jaakko, Lawlor, Deborah A, Lehtimäki, Terho, Lohoff, Falk W, Milani, Lili, Milne, Roger L, Probst-Hensch, Nicole, Reiner, Alex P, Ritz, Beate, and Rotter, Jerome I

Subjects
Prevention, Nutrition, Aging, Human Genome, Genetics, Generic health relevance, Inflammatory and immune system, Good Health and Well Being, Adiposity, Biomarkers, C-Reactive Protein, CpG Islands, DNA Methylation, Educational Status, Epigenesis, Genetic, Genetic Loci, Genetic Markers, Genome, Human, Genome-Wide Association Study, Granulocytes, Humans, Immunity, Innate, Lipid Metabolism, Multifactorial Inheritance, Plasminogen Activator Inhibitor 1, DNA methylation, GWAS, Epigenetic clock, Genetics of DNA Methylation Consortium, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundBiological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.ResultsLeveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.ConclusionThis study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

Published
2021

5. Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

Author

van der Lee, Sven J, Conway, Olivia J, Jansen, Iris, Carrasquillo, Minerva M, Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R, Stringa, Najada, Chen, Jason A, Zettergren, Anna, Andlauer, Till FM, Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E, Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J, Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A, Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart NM, Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, DESGESCO (Dementia Genetics Spanish Consortium), EADB (Alzheimer Disease European DNA biobank), IFGC (International FTD-Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium), RiMod-FTD (Risk and Modifying factors in Fronto-Temporal Dementia), Netherlands Brain Bank (NBB), Boeve, Bradley F, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel JT, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande AL, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild IA, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, and Clarimón, Jordi

Subjects
DESGESCO, EADB, IFGC, IPDGC, RiMod-FTD, Netherlands Brain Bank, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Alzheimer's Disease, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Aging, Parkinson's Disease, Genetics, 2.1 Biological and endogenous factors, Neurological, Neurology & Neurosurgery, Clinical Sciences
Abstract

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.

Published
2020

6. Genome-Wide Epistatic Network Analyses of Semantic Fluency in Older Adults

Author

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
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7. A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

Author

van der Lee, Sven J, Conway, Olivia J, Jansen, Iris, Carrasquillo, Minerva M, Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R, Stringa, Najada, Chen, Jason A, Zettergren, Anna, Andlauer, Till FM, Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E, Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J, Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A, Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart NM, Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, DESGESCO (Dementia Genetics Spanish Consortium), EADB (Alzheimer Disease European DNA biobank), EADB (Alzheimer Disease European DNA biobank), IFGC (International FTD-Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium), RiMod-FTD (Risk and Modifying factors in Fronto-Temporal Dementia), Netherlands Brain Bank (NBB), Boeve, Bradley F, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel JT, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande AL, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild IA, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, and Clarimón, Jordi

Subjects
DESGESCO (Dementia Genetics Spanish Consortium), EADB, EADB, IFGC (International FTD-Genomics Consortium), IPDGC, IPDGC, RiMod-FTD, Netherlands Brain Bank, GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, Alzheimer’s disease, Amyotrophic lateral sclerosis, Dementia with Lewy bodies, Frontotemporal dementia, Longevity, Multiple sclerosis, Neurodegenerative disease, PLCG2, Parkinson’s disease, Phospholipase C Gamma 2, Progressive supranuclear palsy, Alzheimer's disease, Parkinson's disease, Alzheimer's Disease, frontotemporal dementia, dementia with Lewy-bodies, progressive suprauclear palsy, Parkinson's Disease, amyotrophic lateral sclerosis, multiple sclerosis, neurodegenerative disease, longevity, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.

Published
2019

8. Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Author

Metspalu, Andres, Nelis, Mari, Mägi, Reedik, Esko, Tõnu, Trpchevska, Natalia, Freidin, Maxim B., Broer, Linda, Oosterloo, Berthe C., Yao, Shuyang, Zhou, Yitian, Vona, Barbara, Bishop, Charles, Bizaki-Vallaskangas, Argyro, Canlon, Barbara, Castellana, Fabio, Chasman, Daniel I., Cherny, Stacey, Christensen, Kaare, Concas, Maria Pina, Correa, Adolfo, Elkon, Ran, Mengel-From, Jonas, Gao, Yan, Giersch, Anne B.S., Girotto, Giorgia, Gudjonsson, Alexander, Gudnason, Vilmundur, Heard-Costa, Nancy L., Hertzano, Ronna, Hjelmborg, Jacob v.B., Hjerling-Leffler, Jens, Hoffman, Howard J., Kaprio, Jaakko, Kettunen, Johannes, Krebs, Kristi, Kähler, Anna K., Lallemend, Francois, Launer, Lenore J., Lee, I-Min, Leonard, Hampton, Li, Chuan-Ming, Lowenheim, Hubert, Magnusson, Patrik K.E., van Meurs, Joyce, Milani, Lili, Morton, Cynthia C., Mäkitie, Antti, Nalls, Mike A., Nardone, Giuseppe Giovanni, Nygaard, Marianne, Palviainen, Teemu, Pratt, Sheila, Quaranta, Nicola, Rämö, Joel, Saarentaus, Elmo, Sardone, Rodolfo, Satizabal, Claudia L., Schweinfurth, John M., Seshadri, Sudha, Shiroma, Eric, Shulman, Eldad, Simonsick, Eleanor, Spankovich, Christopher, Tropitzsch, Anke, Lauschke, Volker M., Sullivan, Patrick F., Goedegebure, Andre, Cederroth, Christopher R., Williams, Frances M.K., and Nagtegaal, Andries Paul

Published
2022
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13. A Mass Spectrometry-Based Proteome Study of Twin Pairs Discordant for Incident Acute Myocardial Infarction within Three Years after Blood Sampling Suggests Novel Biomarkers.

Author

Beck, Hans Christian, Skovgaard, Asmus Cosmos, Mohammadnejad, Afsaneh, Palstrøm, Nicolai Bjødstrup, Nielsen, Palle Fruekilde, Mengel-From, Jonas, Hjelmborg, Jacob, Rasmussen, Lars Melholt, and Soerensen, Mette

Subjects
MYOCARDIAL infarction, TWIN studies, BLOOD sampling, INDUCTIVELY coupled plasma mass spectrometry, BIOMARKERS
Abstract

Acute myocardial infarction (AMI) is a major cause of mortality and morbidity worldwide, yet biomarkers for AMI in the short- or medium-term are lacking. We apply the discordant twin pair design, reducing genetic and environmental confounding, by linking nationwide registry data on AMI diagnoses to a survey of 12,349 twins, thereby identifying 39 twin pairs (48–79 years) discordant for their first-ever AMI within three years after blood sampling. Mass spectrometry of blood plasma identified 715 proteins. Among 363 proteins with a call rate > 50%, imputation and stratified Cox regression analysis revealed seven significant proteins (FDR < 0.05): FGD6, MCAM, and PIK3CB reflected an increased level in AMI twins relative to their non-AMI co-twins (HR > 1), while LBP, IGHV3-15, C1RL, and APOC4 reflected a decreased level in AMI twins relative to their non-AMI co-twins (HR < 1). Additional 50 proteins were nominally significant (p < 0.05), and bioinformatics analyses of all 57 proteins revealed biology within hemostasis, coagulation cascades, the immune system, and the extracellular matrix. A protein–protein-interaction network revealed Fibronectin 1 as a central hub. Finally, technical validation confirmed MCAM, LBP, C1RL, and APOC3. We put forward novel biomarkers for incident AMI, a part of the proteome field where markers are surprisingly rare and where additional studies are highly needed. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Contributors

Author

Adams, Michelle M., primary, Albinet, Cédric, additional, Alicioglu, Banu, additional, Amami, Paolo, additional, André, Nathalie, additional, Ardic-Avci, Narin Ilgim, additional, Arslanoglou, Elizabeth, additional, Artioli, Guilherme Giannini, additional, Audiffren, Michel, additional, Aydogan, Hande Ozge, additional, Belchí, Francisco Javier, additional, Berman, Marvin H., additional, Bezdicek, Ondrej, additional, Bianco, Cynthia, additional, Boban, Jasmina, additional, Bueno Júnior, Carlos Roberto, additional, Butler, Blake E., additional, Cartelli, Daniele, additional, Casani, Augusto Pietro, additional, Celebi-Birand, Dilan, additional, Chen, Zikuan, additional, Chen, Zeyuan, additional, Chen, Bihong T., additional, Cherry, Katie E., additional, Chicherio, Christian, additional, Chio, Jeshya A., additional, Clavé, Pere, additional, Cogger, Victoria C., additional, Cominetti, Márcia Regina, additional, de Guzman, Ma Fe P., additional, del Moral, Maria Clarissa O., additional, Dolan, Eimear, additional, Dominguez, Jacqueline C., additional, Dommaraju, Premchand, additional, Ebo, Theresa, additional, Edler, Melissa K., additional, Erbaba, Begun, additional, Eskandari-Sedighi, Ghazaleh, additional, Fagot, Delphine, additional, Farajdokht, Fereshteh, additional, Fariñas, Isabel, additional, Felício, Laís Francielle Francisca, additional, Figueiredo, Luiz Felipe da Silva, additional, Fortuna, Karen L., additional, Galindo, Máximo Ibo, additional, Georgousopoulou, Ekavi N., additional, Gokarn, Rahul, additional, Gold, Gabriel, additional, Groetz, Hayley, additional, Gualano, Bruno, additional, Halliday, G.M., additional, Harrington, Erin E., additional, Heidenreich, Claudia, additional, Henčić, Boris, additional, Hernández, Rafael, additional, Herrmann, Björn, additional, Jančić, Jasna, additional, Jeżewski, R.C., additional, Kafaligonul, Hulusi, additional, Karakas, Hakki Muammer, additional, Karoglu-Eravsar, Elif Tugce, additional, Kiosses, Dimitris, additional, Kozic, Dusko, additional, Kövari, Enikö, additional, Kuller, Lewis H., additional, LaRocca, Thomas J., additional, Le Couteur, David G., additional, Lee, Gary Jek Chong, additional, Lertxundi, Unax, additional, López del Amo, Víctor, additional, Luciano de Almeida, Mariana, additional, Mahmoudi, Javad, additional, Malva, João O., additional, Manzine, Patricia Regina, additional, Martins, Beatriz, additional, Matthews, Douglas B., additional, McCormack, Derval, additional, Medrano, Juan, additional, Mellor, Duane D., additional, Meléndez, Juan C., additional, Mengel-From, Jonas, additional, Milić, Jelena, additional, Monkovic, Jody, additional, Monteiro-Junior, Renato Sobral, additional, Moreira, Ricardo, additional, Munger, Emily L., additional, Navari, Elena, additional, Newland, M. Christopher, additional, Novo, João, additional, Oriá, Reinaldo B., additional, O’Keeffe, Fiadhnait, additional, Panagiotakos, Demosthenes B., additional, Pereira, Frederico C., additional, Perez-Villalba, Ana, additional, Peron, Rafaela, additional, Preedy, Victor R., additional, Raghanti, Mary Ann, additional, Raimo, Simona, additional, Rajendram, Rajkumar, additional, Ramírez, Ana López, additional, Raposo, Ramon, additional, Raubenheimer, David, additional, Rawal, Punam, additional, Reese-Melancon, Celinda, additional, Reich, Hannah, additional, Requena, Carmen, additional, Ribeiro, Carlos Fontes, additional, Rodrigues, Ana Carolina de Mello Alves, additional, Rondón García, Luis Miguel, additional, Ruiz Trascastro, Rosa Raquel, additional, Sadigh-Eteghad, Saeed, additional, Salehpour, Farzad, additional, Samardžić, Janko, additional, Santangelo, Gabriella, additional, Satorres, Encarnación, additional, Shen, Andrew N., additional, Shepherd, C.E., additional, Simpson, Stephen J., additional, Solis, Marina Yazigi, additional, Solon-Biet, Samantha M., additional, Stankić, Dunja, additional, Strandberg, Timo E., additional, Suchy-Dicey, Astrid M., additional, Tapia, Andrea, additional, Thurnher, Majda M., additional, Álvarez-Merino, Paula, additional, Tomsen, Noemí, additional, Trojano, Luigi, additional, Tuz-Sasik, Melek Umay, additional, Urbanski, Henryk F., additional, Ureshino, Rodrigo Portes, additional, van Beeck, Ed, additional, Van Skike, Candice E., additional, Vatanabe, Izabela Pereira, additional, Wahl, Devin, additional, Westaway, David, additional, Wong, Shawn, additional, Wu, Long, additional, Xavier-Rocha, Túlio Brandão, additional, Zeković, Janko, additional, Zhang, Xin, additional, and Zhao, Liqin, additional

Published
2021
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23. Identifying genetic variants regulating MGMT gene expression - A study in monozygotic Danish twins

Author

Mohammadnejad, Afsaneh, primary, Soerensen, Mette, additional, Mengel-From, Jonas, additional, Nygaard, Marianne, additional, Timofeeva, Maria, additional, He, Liang, additional, Clemmensen, Signe Bedsted, additional, Halekoh, Ulrich, additional, Dahlrot, Rikke Hedegaard, additional, Tan, Qihua, additional, and Hjelmborg, Jacob v.B., additional

Published
2023
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26. A Review of Major Danish Biobanks: Advantages and Possibilities of Health Research in Denmark

Author

Laugesen, Kristina, primary, Mengel-From, Jonas, additional, Christensen, Kaare, additional, Olsen, Jørn, additional, Hougaard, David M, additional, Boding, Lasse, additional, Olsen, Anja, additional, Erikstrup, Christian, additional, Hetland, Merete Lund, additional, Høgdall, Estrid, additional, Kjaergaard, Alisa D, additional, Sørensen, Erik, additional, Brügmann, Anja, additional, Petersen, Eva Rabing Brix, additional, Brandslund, Ivan, additional, Nordestgaard, Børge G, additional, Jensen, Gorm B, additional, Skajaa, Nils, additional, Troelsen, Frederikke Schønfeldt, additional, Fuglsang, Cecilia Hvitfeldt, additional, Svingel, Lise Skovgaard, additional, and Sørensen, Henrik T, additional

Published
2023
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27. A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants

Author

Bae, Harold, primary, Gurinovich, Anastasia, additional, Karagiannis, Tanya T., additional, Song, Zeyuan, additional, Leshchyk, Anastasia, additional, Li, Mengze, additional, Andersen, Stacy L., additional, Arbeev, Konstantin, additional, Yashin, Anatoliy, additional, Zmuda, Joseph, additional, An, Ping, additional, Feitosa, Mary, additional, Giuliani, Cristina, additional, Franceschi, Claudio, additional, Garagnani, Paolo, additional, Mengel-From, Jonas, additional, Atzmon, Gil, additional, Barzilai, Nir, additional, Puca, Annibale, additional, Schork, Nicholas J., additional, Perls, Thomas T., additional, and Sebastiani, Paola, additional

Published
2022
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28. Integrative analysis of clinical and epigenetic biomarkers of mortality

Author

Huan, Tianxiao, Nguyen, Steve, Colicino, Elena, Ochoa-Rosales, Carolina, Hill, W David, Brody, Jennifer A, Soerensen, Mette, Zhang, Yan, Baldassari, Antoine, Elhadad, Mohamed Ahmed, Toshiko, Tanaka, Zheng, Yinan, Domingo-Relloso, Arce, Lee, Dong Heon, Ma, Jiantao, Yao, Chen, Liu, Chunyu, Hwang, Shih-Jen, Joehanes, Roby, Fornage, Myriam, Bressler, Jan, van Meurs, Joyce B J, Debrabant, Birgit, Mengel-From, Jonas, Hjelmborg, Jacob, Christensen, Kaare, Vokonas, Pantel, Schwartz, Joel, Gahrib, Sina A, Sotoodehnia, Nona, Sitlani, Colleen M, Kunze, Sonja, Gieger, Christian, Peters, Annette, Waldenberger, Melanie, Deary, Ian J, Ferrucci, Luigi, Qu, Yishu, Greenland, Philip, Lloyd-Jones, Donald M, Hou, Lifang, Bandinelli, Stefania, Voortman, Trudy, Hermann, Brenner, Baccarelli, Andrea, Whitsel, Eric, Pankow, James S, Levy, Daniel, Ochoa‐Rosales, Carolina, Hill, W. David, Brody, Jennifer A., Domingo‐Relloso, Arce, Hwang, Shih‐Jen, van Meurs, Joyce B.J., Mengel‐From, Jonas, Gahrib, Sina A., Sitlani, Colleen M., Deary, Ian J., Lloyd‐Jones, Donald M., Pankow, James S., Meurs, Joyce B.J., National Institutes of Health (Estados Unidos), NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos), NIH - Center for Information Technology (Estados Unidos), NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos), NIH - National Institute on Aging (NIA) (Estados Unidos), Fundación Merck Salud, Laughlin Family, Alpha Phi Foundation, Locke Charitable Foundation, National Center for Advancing Translational Sciences (Estados Unidos), NIH - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (Estados Unidos), Danish Council for Independent Research, Unión Europea. Comisión Europea. 7 Programa Marco, United States of Department of Health & Human Services, NIH - National Institute of Environmental Health Sciences (NIEHS) (Estados Unidos), Biotechnology and Biological Sciences Research Council (Reino Unido), Royal Society (Reino Unido), Scottish Government, Age UK (Reino Unido), Centre for Cognitive Ageing and Cognitive Epidemiology (Reino Unido), Wellcome Trust, University of Edinburgh (Reino Unido), University of Queensland (Australia), Medical Research Council (Reino Unido), United States Department of Veterans Affairs, Massachusetts Veterans Education Research and Information Center (MAVERIC), Epidemiology, and Internal Medicine

Subjects
Epigenomics, Male, Aging, DNA methylation, Cell Biology, DNA Methylation, Cardiovascular disease, Epigenesis, Genetic, SDG 3 - Good Health and Well-being, Cardiovascular Diseases, Neoplasms, Machine learning, Humans, Mortality, Dna Methylation, Cancer, Cardiovascular Disease, Machine Learning, Biomarkers
Abstract

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p

Published
2022

33. Long-Lived Individuals Show a Lower Burden of Variants Predisposing to Age-Related Diseases and a Higher Polygenic Longevity Score

Author

Torres, Guillermo G., primary, Dose, Janina, additional, Hasenbein, Tim P., additional, Nygaard, Marianne, additional, Krause-Kyora, Ben, additional, Mengel-From, Jonas, additional, Christensen, Kaare, additional, Andersen-Ranberg, Karen, additional, Kolbe, Daniel, additional, Lieb, Wolfgang, additional, Laudes, Matthias, additional, Görg, Siegfried, additional, Schreiber, Stefan, additional, Franke, Andre, additional, Caliebe, Amke, additional, Kuhlenbäumer, Gregor, additional, and Nebel, Almut, additional

Published
2022
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36. Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Author

Trpchevska, Natalia, primary, Freidin, Maxim B., additional, Broer, Linda, additional, Oosterloo, Berthe C., additional, Yao, Shuyang, additional, Zhou, Yitian, additional, Vona, Barbara, additional, Bishop, Charles, additional, Bizaki-Vallaskangas, Argyro, additional, Canlon, Barbara, additional, Castellana, Fabio, additional, Chasman, Daniel I., additional, Cherny, Stacey, additional, Christensen, Kaare, additional, Concas, Maria Pina, additional, Correa, Adolfo, additional, Elkon, Ran, additional, Mengel-From, Jonas, additional, Gao, Yan, additional, Giersch, Anne B.S., additional, Girotto, Giorgia, additional, Gudjonsson, Alexander, additional, Gudnason, Vilmundur, additional, Heard-Costa, Nancy L., additional, Hertzano, Ronna, additional, Hjelmborg, Jacob v.B., additional, Hjerling-Leffler, Jens, additional, Hoffman, Howard J., additional, Kaprio, Jaakko, additional, Kettunen, Johannes, additional, Krebs, Kristi, additional, Kähler, Anna K., additional, Lallemend, Francois, additional, Launer, Lenore J., additional, Lee, I-Min, additional, Leonard, Hampton, additional, Li, Chuan-Ming, additional, Lowenheim, Hubert, additional, Magnusson, Patrik K.E., additional, van Meurs, Joyce, additional, Milani, Lili, additional, Morton, Cynthia C., additional, Mäkitie, Antti, additional, Nalls, Mike A., additional, Nardone, Giuseppe Giovanni, additional, Nygaard, Marianne, additional, Palviainen, Teemu, additional, Pratt, Sheila, additional, Quaranta, Nicola, additional, Rämö, Joel, additional, Saarentaus, Elmo, additional, Sardone, Rodolfo, additional, Satizabal, Claudia L., additional, Schweinfurth, John M., additional, Seshadri, Sudha, additional, Shiroma, Eric, additional, Shulman, Eldad, additional, Simonsick, Eleanor, additional, Spankovich, Christopher, additional, Tropitzsch, Anke, additional, Lauschke, Volker M., additional, Sullivan, Patrick F., additional, Goedegebure, Andre, additional, Cederroth, Christopher R., additional, Williams, Frances M.K., additional, Nagtegaal, Andries Paul, additional, Metspalu, Andres, additional, Nelis, Mari, additional, Mägi, Reedik, additional, and Esko, Tõnu, additional

Published
2022
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38. A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants.

Author

Bae, Harold, Gurinovich, Anastasia, Karagiannis, Tanya T., Song, Zeyuan, Leshchyk, Anastasia, Li, Mengze, Andersen, Stacy L., Arbeev, Konstantin, Yashin, Anatoliy, Zmuda, Joseph, An, Ping, Feitosa, Mary, Giuliani, Cristina, Franceschi, Claudio, Garagnani, Paolo, Mengel-From, Jonas, Atzmon, Gil, Barzilai, Nir, Puca, Annibale, and Schork, Nicholas J.

Subjects
LONGEVITY, GENOME-wide association studies, GENETIC variation, ALZHEIMER'S disease, BLOOD proteins, GENE frequency, EXOMES
Abstract

We performed a genome-wide association study (GWAS) of human extreme longevity (EL), defined as surviving past the 99th survival percentile, by aggregating data from four centenarian studies. The combined data included 2304 EL cases and 5879 controls. The analysis identified a locus in CDKN2B-AS1 (rs6475609, p = 7.13 × 10−8) that almost reached genome-wide significance and four additional loci that were suggestively significant. Among these, a novel rare variant (rs145265196) on chromosome 11 had much higher longevity allele frequencies in cases of Ashkenazi Jewish and Southern Italian ancestry compared to cases of other European ancestries. We also correlated EL-associated SNPs with serum proteins to link our findings to potential biological mechanisms that may be related to EL and are under genetic regulation. The findings from the proteomic analyses suggested that longevity-promoting alleles of significant genetic variants either provided EL cases with more youthful molecular profiles compared to controls or provided some form of protection from other illnesses, such as Alzheimer's disease, and disease progressions. [ABSTRACT FROM AUTHOR]

Published
2023
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39. An integrative analysis of clinical and epigenetic biomarkers of mortality

Author

Huan, Tianxiao, primary, Nguyen, Steve, additional, Colicino, Elena, additional, Ochoa-Rosales, Carolina, additional, Hill, William David, additional, Brody, Jennifer A, additional, Soerensen, Mette, additional, Zhang, Yan, additional, Baldassari, Antoine, additional, Elhadad, Mohamed Ahmed, additional, Toshiko, Tanaka, additional, Zheng, Yinan, additional, Domingo-Relloso, Arce, additional, Lee, Dong Heon, additional, Ma, Jiantao, additional, Yao, Chen, additional, Liu, Chunyu, additional, Hwang, Shih-Jen, additional, Joehanes, Roby, additional, Fornage, Myriam, additional, Bressler, Jan, additional, van Meurs, Joyce BJ, additional, Debrabant, Birgit, additional, Mengel-From, Jonas, additional, Hjelmborg, Jacob, additional, Christensen, Kaare, additional, Vokonas, Pantel, additional, Schwartz, Joel, additional, Gahrib, Sina A, additional, Sotoodehnia, Nona, additional, Sitlani, Colleen, additional, Kunze, Sonja, additional, Gieger, Christian, additional, Peters, Annette, additional, Waldenberger, Melanie, additional, Deary, Ian J, additional, Ferrucci, Luigi, additional, Qu, Yishu, additional, Greenland, Philip, additional, Lloyd-Jones, Donald M, additional, Hou, Lifang, additional, Bandinelli, Stefania, additional, Voortman, Trudy, additional, Hermann, Brenner, additional, Baccarelli, Andrea, additional, Whitsel, Eric, additional, Pankow, James S, additional, and Levy, Daniel, additional

Published
2022
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40. Rare Genetic Variants Correlate with Better Processing Speed

Author

Song, Zeyuan, primary, Gurinovich, Anastasia, additional, Nygaard, Marianne, additional, Mengel-From, Jonas, additional, Andersen, Stacy, additional, Cosentino, Stephanie, additional, Schupfs, Nicole, additional, Lee, Joseph, additional, Zmuda, Joseph, additional, Ukraintseva, Svetlana, additional, Arbeev, Konstantin, additional, Christensen, Kaare, additional, Perls, Thomas, additional, and Sebastiani, Paola, additional

Published
2022
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49. Global Gene Expression Profiling and Transcription Factor Network Analysis of Cognitive Aging in Monozygotic Twins

Author

Mohammadnejad, Afsaneh, primary, Li, Weilong, additional, Lund, Jesper Beltoft, additional, Li, Shuxia, additional, Larsen, Martin J., additional, Mengel-From, Jonas, additional, Michel, Tanja Maria, additional, Christiansen, Lene, additional, Christensen, Kaare, additional, Hjelmborg, Jacob, additional, Baumbach, Jan, additional, and Tan, Qihua, additional

Published
2021
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50. Additional file 1 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Author

McCartney, Daniel L., Min, Josine L., Richmond, Rebecca C., Lu, Ake T., Sobczyk, Maria K., Davies, Gail, Broer, Linda, Guo, Xiuqing, Jeong, Ayoung, Jung, Jeesun, Kasela, Silva, Katrinli, Seyma, Kuo, Pei-Lun, Matias-Garcia, Pamela R., Mishra, Pashupati P., Nygaard, Marianne, Palviainen, Teemu, Patki, Amit, Raffield, Laura M., Ratliff, Scott M., Richardson, Tom G., Robinson, Oliver, Soerensen, Mette, Sun, Dianjianyi, Tsai, Pei-Chien, van der Zee, Matthijs D., Walker, Rosie M., Wang, Xiaochuan, Wang, Yunzhang, Xia, Rui, Xu, Zongli, Yao, Jie, Zhao, Wei, Correa, Adolfo, Boerwinkle, Eric, Dugué, Pierre-Antoine, Durda, Peter, Elliott, Hannah R., Gieger, Christian, de Geus, Eco J. C., Harris, Sarah E., Hemani, Gibran, Imboden, Medea, Kähönen, Mika, Kardia, Sharon L. R., Kresovich, Jacob K., Li, Shengxu, Lunetta, Kathryn L., Mangino, Massimo, Mason, Dan, McIntosh, Andrew M., Mengel-From, Jonas, Moore, Ann Zenobia, Murabito, Joanne M., Ollikainen, Miina, Pankow, James S., Pedersen, Nancy L., Peters, Annette, Polidoro, Silvia, Porteous, David J., Raitakari, Olli, Rich, Stephen S., Sandler, Dale P., Sillanpää, Elina, Smith, Alicia K., Southey, Melissa C., Strauch, Konstantin, Tiwari, Hemant, Tanaka, Toshiko, Tillin, Therese, Uitterlinden, Andre G., Van Den Berg, David J., van Dongen, Jenny, Wilson, James G., Wright, John, Yet, Idil, Arnett, Donna, Bandinelli, Stefania, Bell, Jordana T., Binder, Alexandra M., Boomsma, Dorret I., Chen, Wei, Christensen, Kaare, Conneely, Karen N., Elliott, Paul, Ferrucci, Luigi, Fornage, Myriam, Hägg, Sara, Hayward, Caroline, Irvin, Marguerite, Kaprio, Jaakko, Lawlor, Deborah A., Lehtimäki, Terho, Lohoff, Falk W., Milani, Lili, Milne, Roger L., Probst-Hensch, Nicole, Reiner, Alex P., Ritz, Beate, Rotter, Jerome I., Smith, Jennifer A., Taylor, Jack A., van Meurs, Joyce B. J., Vineis, Paolo, Waldenberger, Melanie, Deary, Ian J., Relton, Caroline L., Horvath, Steve, and Marioni, Riccardo E.

Abstract

Additional file 1. Individual cohort descriptions and acknowledgements.

Published
2021
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