777 results on '"Atzmon, Gil"'
Search Results
2. Correction to: Genome integrity as a potential index of longevity in Ashkenazi Centenarian’s families
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Andrawus, Mariana, David, Gil Ben, Terziyska, Ivana, Sharvit, Lital, Bergman, Aviv, Barzilai, Nir, Raj, Srilakshmi M., Govindaraju, Diddahally R., and Atzmon, Gil
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- 2024
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3. The d3GHR carrier epigenome in Druze clan longevity
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Falah, Ghadeer, Kurolap, Alina, Paperna, Tamar, Ekhilevitch, Nina, Moustafa, Nivin, Damouny-Naoum, Nadine, Amir, Yam, Sharvit, Lital, Moghrabi, Rihan, Hassoun, Gamal, Fares, Fuad, Baris Feldman, Hagit, and Atzmon, Gil
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- 2024
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4. Polygenic prediction of human longevity on the supposition of pervasive pleiotropy
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Jabalameli, M. Reza, Lin, Jhih-Rong, Zhang, Quanwei, Wang, Zhen, Mitra, Joydeep, Nguyen, Nha, Gao, Tina, Khusidman, Mark, Sathyan, Sanish, Atzmon, Gil, Milman, Sofiya, Vijg, Jan, Barzilai, Nir, and Zhang, Zhengdong D.
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- 2024
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5. Author Correction: Rare genetic coding variants associated with human longevity and protection against age-related diseases
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Lin, Jhih-Rong, Sin-Chan, Patrick, Napolioni, Valerio, Torres, Guillermo G., Mitra, Joydeep, Zhang, Quanwei, Jabalameli, M. Reza, Wang, Zhen, Nguyen, Nha, Gao, Tina, Laudes, Matthias, Görg, Siegfried, Franke, Andre, Nebel, Almut, Greicius, Michael D., Atzmon, Gil, Ye, Kenny, Gorbunova, Vera, Ladiges, Warren C., Shuldiner, Alan R., Niedernhofer, Laura J., Robbins, Paul D., Milman, Sofiya, Suh, Yousin, Vijg, Jan, Barzilai, Nir, and Zhang, Zhengdong D.
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- 2024
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6. CRISPR-Cas9 mediated d3GHR knockout in HEK293 cells: Revealing the longevity associated isoform stress resilience
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Falah, Ghadeer, Sharvit, Lital, and Atzmon, Gil
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- 2024
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7. High-throughput sequencing analysis of nuclear-encoded mitochondrial genes reveals a genetic signature of human longevity
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Gonzalez, Brenda, Tare, Archana, Ryu, Seungjin, Johnson, Simon C., Atzmon, Gil, Barzilai, Nir, Kaeberlein, Matt, and Suh, Yousin
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- 2023
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8. Genetic signature of human longevity in PKC and NF‐κB signaling
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Ryu, Seungjin, Han, Jeehae, Norden‐Krichmar, Trina M, Zhang, Quanwei, Lee, Seunggeun, Zhang, Zhengdong, Atzmon, Gil, Niedernhofer, Laura J, Robbins, Paul D, Barzilai, Nir, Schork, Nicholas J, and Suh, Yousin
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Brain Disorders ,Biotechnology ,Alzheimer's Disease ,Aging ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Acquired Cognitive Impairment ,Dementia ,Neurodegenerative ,Genetics ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Genetic Variation ,Humans ,Longevity ,NF-kappa B ,Peptide Fragments ,Protein Kinase C ,Signal Transduction ,centenarian ,genetic variant ,longevity ,PKC ,rare variant ,NF-κB ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Gene variants associated with longevity are also associated with protection against cognitive decline, dementia and Alzheimer's disease, suggesting that common physiologic pathways act at the interface of longevity and cognitive function. To test the hypothesis that variants in genes implicated in cognitive function may promote exceptional longevity, we performed a comprehensive 3-stage study to identify functional longevity-associated variants in ~700 candidate genes in up to 450 centenarians and 500 controls by target capture sequencing analysis. We found an enrichment of longevity-associated genes in the nPKC and NF-κB signaling pathways by gene-based association analyses. Functional analysis of the top three gene variants (NFKBIA, CLU, PRKCH) suggests that non-coding variants modulate the expression of cognate genes, thereby reducing signaling through the nPKC and NF-κB. This matches genetic studies in multiple model organisms, suggesting that the evolutionary conservation of reduced PKC and NF-κB signaling pathways in exceptional longevity may include humans.
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- 2021
9. Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.
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Goodrich, Julia K, Singer-Berk, Moriel, Son, Rachel, Sveden, Abigail, Wood, Jordan, England, Eleina, Cole, Joanne B, Weisburd, Ben, Watts, Nick, Caulkins, Lizz, Dornbos, Peter, Koesterer, Ryan, Zappala, Zachary, Zhang, Haichen, Maloney, Kristin A, Dahl, Andy, Aguilar-Salinas, Carlos A, Atzmon, Gil, Barajas-Olmos, Francisco, Barzilai, Nir, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Bowden, Donald W, Centeno-Cruz, Federico, Chambers, John C, Chami, Nathalie, Chan, Edmund, Chan, Juliana, Cheng, Ching-Yu, Cho, Yoon Shin, Contreras-Cubas, Cecilia, Córdova, Emilio, Correa, Adolfo, DeFronzo, Ralph A, Duggirala, Ravindranath, Dupuis, Josée, Garay-Sevilla, Ma Eugenia, García-Ortiz, Humberto, Gieger, Christian, Glaser, Benjamin, González-Villalpando, Clicerio, Gonzalez, Ma Elena, Grarup, Niels, Groop, Leif, Gross, Myron, Haiman, Christopher, Han, Sohee, Hanis, Craig L, Hansen, Torben, Heard-Costa, Nancy L, Henderson, Brian E, Hernandez, Juan Manuel Malacara, Hwang, Mi Yeong, Islas-Andrade, Sergio, Jørgensen, Marit E, Kang, Hyun Min, Kim, Bong-Jo, Kim, Young Jin, Koistinen, Heikki A, Kooner, Jaspal Singh, Kuusisto, Johanna, Kwak, Soo-Heon, Laakso, Markku, Lange, Leslie, Lee, Jong-Young, Lee, Juyoung, Lehman, Donna M, Linneberg, Allan, Liu, Jianjun, Loos, Ruth JF, Lyssenko, Valeriya, Ma, Ronald CW, Martínez-Hernández, Angélica, Meigs, James B, Meitinger, Thomas, Mendoza-Caamal, Elvia, Mohlke, Karen L, Morris, Andrew D, Morrison, Alanna C, Ng, Maggie CY, Nilsson, Peter M, O'Donnell, Christopher J, Orozco, Lorena, Palmer, Colin NA, Park, Kyong Soo, Post, Wendy S, Pedersen, Oluf, Preuss, Michael, Psaty, Bruce M, Reiner, Alexander P, Revilla-Monsalve, Cristina, Rich, Stephen S, Rotter, Jerome I, Saleheen, Danish, Schurmann, Claudia, Sim, Xueling, Sladek, Rob, and Small, Kerrin S
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AMP-T2D-GENES Consortia ,Humans ,Diabetes Mellitus ,Type 2 ,Genetic Predisposition to Disease ,Risk Assessment ,Genotype ,Multifactorial Inheritance ,Penetrance ,Adult ,Dyslipidemias ,Exome ,Biomarkers ,Biological Variation ,Population - Abstract
Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.
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- 2021
10. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan
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Yen, Kelvin, Mehta, Hemal H, Kim, Su-Jeong, Lue, YanHe, Hoang, James, Guerrero, Noel, Port, Jenna, Bi, Qiuli, Navarrete, Gerardo, Brandhorst, Sebastian, Lewis, Kaitlyn Noel, Wan, Junxiang, Swerdloff, Ronald, Mattison, Julie A, Buffenstein, Rochelle, Breton, Carrie V, Wang, Christina, Longo, Valter, Atzmon, Gil, Wallace, Douglas, Barzilai, Nir, and Cohen, Pinchas
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Biochemistry and Cell Biology ,Biological Sciences ,Genetics ,Brain Disorders ,Aging ,Adult ,Aged ,80 and over ,Alzheimer Disease ,Animals ,Animals ,Genetically Modified ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Case-Control Studies ,Child ,Cohort Studies ,DNA ,Mitochondrial ,Female ,Forkhead Transcription Factors ,Gene Dosage ,Humans ,Infant ,Newborn ,Intracellular Signaling Peptides and Proteins ,Longevity ,MELAS Syndrome ,Macaca mulatta ,Mice ,Middle Aged ,Mitochondria ,Models ,Animal ,Mole Rats ,Pregnancy ,Young Adult ,aging ,mitochondria ,peptides ,humanin ,Biochemistry and cell biology ,Clinical sciences - Abstract
Humanin is a member of a new family of peptides that are encoded by short open reading frames within the mitochondrial genome. It is conserved in animals and is both neuroprotective and cytoprotective. Here we report that in C. elegans the overexpression of humanin is sufficient to increase lifespan, dependent on daf-16/Foxo. Humanin transgenic mice have many phenotypes that overlap with the worm phenotypes and, similar to exogenous humanin treatment, have increased protection against toxic insults. Treating middle-aged mice twice weekly with the potent humanin analogue HNG, humanin improves metabolic healthspan parameters and reduces inflammatory markers. In multiple species, humanin levels generally decline with age, but here we show that levels are surprisingly stable in the naked mole-rat, a model of negligible senescence. Furthermore, in children of centenarians, who are more likely to become centenarians themselves, circulating humanin levels are much greater than age-matched control subjects. Further linking humanin to healthspan, we observe that humanin levels are decreased in human diseases such as Alzheimer's disease and MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes). Together, these studies are the first to demonstrate that humanin is linked to improved healthspan and increased lifespan.
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- 2020
11. Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility
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Sazonovs, Aleksejs, Stevens, Christine R., Venkataraman, Guhan R., Yuan, Kai, Avila, Brandon, Abreu, Maria T., Ahmad, Tariq, Allez, Matthieu, Ananthakrishnan, Ashwin N., Atzmon, Gil, Baras, Aris, Barrett, Jeffrey C., Barzilai, Nir, Beaugerie, Laurent, Beecham, Ashley, Bernstein, Charles N., Bitton, Alain, Bokemeyer, Bernd, Chan, Andrew, Chung, Daniel, Cleynen, Isabelle, Cosnes, Jacques, Cutler, David J., Daly, Allan, Damas, Oriana M., Datta, Lisa W., Dawany, Noor, Devoto, Marcella, Dodge, Sheila, Ellinghaus, Eva, Fachal, Laura, Farkkila, Martti, Faubion, William, Ferreira, Manuel, Franchimont, Denis, Gabriel, Stacey B., Ge, Tian, Georges, Michel, Gettler, Kyle, Giri, Mamta, Glaser, Benjamin, Goerg, Siegfried, Goyette, Philippe, Graham, Daniel, Hämäläinen, Eija, Haritunians, Talin, Heap, Graham A., Hiltunen, Mikko, Hoeppner, Marc, Horowitz, Julie E., Irving, Peter, Iyer, Vivek, Jalas, Chaim, Kelsen, Judith, Khalili, Hamed, Kirschner, Barbara S., Kontula, Kimmo, Koskela, Jukka T., Kugathasan, Subra, Kupcinskas, Juozas, Lamb, Christopher A., Laudes, Matthias, Lévesque, Chloé, Levine, Adam P., Lewis, James D., Liefferinckx, Claire, Loescher, Britt-Sabina, Louis, Edouard, Mansfield, John, May, Sandra, McCauley, Jacob L., Mengesha, Emebet, Mni, Myriam, Moayyedi, Paul, Moran, Christopher J., Newberry, Rodney D., O’Charoen, Sirimon, Okou, David T., Oldenburg, Bas, Ostrer, Harry, Palotie, Aarno, Paquette, Jean, Pekow, Joel, Peter, Inga, Pierik, Marieke J., Ponsioen, Cyriel Y., Pontikos, Nikolas, Prescott, Natalie, Pulver, Ann E., Rahmouni, Souad, Rice, Daniel L., Saavalainen, Päivi, Sands, Bruce, Sartor, R. Balfour, Schiff, Elena R., Schreiber, Stefan, Schumm, L. Philip, Segal, Anthony W., Seksik, Philippe, Shawky, Rasha, Sheikh, Shehzad Z., Silverberg, Mark S., Simmons, Alison, Skeiceviciene, Jurgita, Sokol, Harry, Solomonson, Matthew, Somineni, Hari, Sun, Dylan, Targan, Stephan, Turner, Dan, Uhlig, Holm H., van der Meulen, Andrea E., Vermeire, Séverine, Verstockt, Sare, Voskuil, Michiel D., Winter, Harland S., Young, Justine, Duerr, Richard H., Franke, Andre, Brant, Steven R., Cho, Judy, Weersma, Rinse K., Parkes, Miles, Xavier, Ramnik J., Rivas, Manuel A., Rioux, John D., McGovern, Dermot P. B., Huang, Hailiang, Anderson, Carl A., and Daly, Mark J.
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- 2022
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12. A meta-analysis of genome-wide association studies identifies multiple longevity genes.
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Deelen, Joris, Evans, Daniel S, Arking, Dan E, Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K, Biggs, Mary L, van der Spek, Ashley, Atzmon, Gil, Ware, Erin B, Sarnowski, Chloé, Smith, Albert V, Seppälä, Ilkka, Cordell, Heather J, Dose, Janina, Amin, Najaf, Arnold, Alice M, Ayers, Kristin L, Barzilai, Nir, Becker, Elizabeth J, Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C, Cubaynes, Sarah, Cummings, Steven R, Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D, Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B, Huisman, Martijn, Hurme, Mikko A, Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon LR, Kingston, Andrew, Kirkwood, Thomas BL, Launer, Lenore J, Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B, Nie, Chao, Nohr, Ellen A, Orwoll, Eric S, Perls, Thomas T, Province, Michael A, Psaty, Bruce M, Raitakari, Olli T, Reinders, Marcel JT, Robine, Jean-Marie, Rotter, Jerome I, Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild IA, Taylor, Kent D, Uitterlinden, André G, van der Flier, Wiesje, van der Lee, Sven J, van Duijn, Cornelia M, van Heemst, Diana, Vaupel, James W, Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P, Lunetta, Kathryn L, Slagboom, P Eline, and Murabito, Joanne M
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Humans ,Heat-Shock Proteins ,Longevity ,Apolipoprotein E2 ,Apolipoprotein E4 ,Genome-Wide Association Study - Abstract
Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
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- 2019
13. Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls
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Flannick, Jason, Mercader, Josep M, Fuchsberger, Christian, Udler, Miriam S, Mahajan, Anubha, Wessel, Jennifer, Teslovich, Tanya M, Caulkins, Lizz, Koesterer, Ryan, Barajas-Olmos, Francisco, Blackwell, Thomas W, Boerwinkle, Eric, Brody, Jennifer A, Centeno-Cruz, Federico, Chen, Ling, Chen, Siying, Contreras-Cubas, Cecilia, Córdova, Emilio, Correa, Adolfo, Cortes, Maria, DeFronzo, Ralph A, Dolan, Lawrence, Drews, Kimberly L, Elliott, Amanda, Floyd, James S, Gabriel, Stacey, Garay-Sevilla, Maria Eugenia, García-Ortiz, Humberto, Gross, Myron, Han, Sohee, Heard-Costa, Nancy L, Jackson, Anne U, Jørgensen, Marit E, Kang, Hyun Min, Kelsey, Megan, Kim, Bong-Jo, Koistinen, Heikki A, Kuusisto, Johanna, Leader, Joseph B, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Lyssenko, Valeriya, Manning, Alisa K, Marcketta, Anthony, Malacara-Hernandez, Juan Manuel, Martínez-Hernández, Angélica, Matsuo, Karen, Mayer-Davis, Elizabeth, Mendoza-Caamal, Elvia, Mohlke, Karen L, Morrison, Alanna C, Ndungu, Anne, Ng, Maggie CY, O’Dushlaine, Colm, Payne, Anthony J, Pihoker, Catherine, Post, Wendy S, Preuss, Michael, Psaty, Bruce M, Vasan, Ramachandran S, Rayner, N William, Reiner, Alexander P, Revilla-Monsalve, Cristina, Robertson, Neil R, Santoro, Nicola, Schurmann, Claudia, So, Wing Yee, Soberón, Xavier, Stringham, Heather M, Strom, Tim M, Tam, Claudia HT, Thameem, Farook, Tomlinson, Brian, Torres, Jason M, Tracy, Russell P, van Dam, Rob M, Vujkovic, Marijana, Wang, Shuai, Welch, Ryan P, Witte, Daniel R, Wong, Tien-Yin, Atzmon, Gil, Barzilai, Nir, Blangero, John, Bonnycastle, Lori L, Bowden, Donald W, Chambers, John C, Chan, Edmund, Cheng, Ching-Yu, Cho, Yoon Shin, Collins, Francis S, de Vries, Paul S, Duggirala, Ravindranath, Glaser, Benjamin, Gonzalez, Clicerio, Gonzalez, Ma Elena, Groop, Leif, Kooner, Jaspal Singh, and Kwak, Soo Heon
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Prevention ,Biotechnology ,Diabetes ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Animals ,Case-Control Studies ,Decision Support Techniques ,Diabetes Mellitus ,Type 2 ,Exome ,Female ,Gene Frequency ,Genome-Wide Association Study ,Humans ,Male ,Mice ,Mice ,Knockout ,Exome Sequencing ,Broad Genomics Platform ,DiscovEHR Collaboration ,CHARGE ,LuCamp ,ProDiGY ,GoT2D ,ESP ,SIGMA-T2D ,T2D-GENES ,AMP-T2D-GENES ,General Science & Technology - Abstract
Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10-3) and candidate genes from knockout mice (P = 5.2 × 10-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.
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- 2019
14. Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies
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Yu, Dongmei, Sul, Jae Hoon, Tsetsos, Fotis, Nawaz, Muhammad S, Huang, Alden Y, Zelaya, Ivette, Illmann, Cornelia, Osiecki, Lisa, Darrow, Sabrina M, Hirschtritt, Matthew E, Greenberg, Erica, Muller-Vahl, Kirsten R, Stuhrmann, Manfred, Dion, Yves, Rouleau, Guy, Aschauer, Harald, Stamenkovic, Mara, Schlögelhofer, Monika, Sandor, Paul, Barr, Cathy L, Grados, Marco, Singer, Harvey S, Nöthen, Markus M, Hebebrand, Johannes, Hinney, Anke, King, Robert A, Fernandez, Thomas V, Barta, Csaba, Tarnok, Zsanett, Nagy, Peter, Depienne, Christel, Worbe, Yulia, Hartmann, Andreas, Budman, Cathy L, Rizzo, Renata, Lyon, Gholson J, McMahon, William M, Batterson, James R, Cath, Danielle C, Malaty, Irene A, Okun, Michael S, Berlin, Cheston, Woods, Douglas W, Lee, Paul C, Jankovic, Joseph, Robertson, Mary M, Gilbert, Donald L, Brown, Lawrence W, Coffey, Barbara J, Dietrich, Andrea, Hoekstra, Pieter J, Kuperman, Samuel, Zinner, Samuel H, Luðvigsson, Pétur, Sæmundsen, Evald, Thorarensen, Ólafur, Atzmon, Gil, Barzilai, Nir, Wagner, Michael, Moessner, Rainald, Ophoff, Roel, Pato, Carlos N, Pato, Michele T, Knowles, James A, Roffman, Joshua L, Smoller, Jordan W, Buckner, Randy L, Willsey, A Jeremy, Tischfield, Jay A, Heiman, Gary A, Stefansson, Hreinn, Stefansson, Kári, Posthuma, Danielle, Cox, Nancy J, Pauls, David L, Freimer, Nelson B, Neale, Benjamin M, Davis, Lea K, Paschou, Peristera, Coppola, Giovanni, Mathews, Carol A, and Scharf, Jeremiah M
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Mental Health ,Prevention ,Brain Disorders ,Human Genome ,Neurosciences ,Neurodegenerative ,Serious Mental Illness ,Tourette Syndrome ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Case-Control Studies ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Multifactorial Inheritance ,Polymorphism ,Single Nucleotide ,Risk Factors ,Severity of Illness Index ,Tic Disorders ,fms-Like Tyrosine Kinase 3 ,Tourette Association of America International Consortium for Genetics ,the Gilles de la Tourette GWAS Replication Initiative ,the Tourette International Collaborative Genetics Study ,and the Psychiatric Genomics Consortium Tourette Syndrome Working Group ,Child Psychiatry ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
ObjectiveTourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity.MethodsGWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined.ResultsGWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects.ConclusionsModulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.
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- 2019
15. Genomics of Aging and Longevity
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Falah, Ghadeer, Gutman, Danielle, Atzmon, Gil, Govindaraju, Diddahally R., Section editor, Gu, Danan, editor, and Dupre, Matthew E., editor
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- 2021
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16. Insights into the genetic epidemiology of Crohns and rare diseases in the Ashkenazi Jewish population.
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Rivas, Manuel, Avila, Brandon, Koskela, Jukka, Huang, Hailiang, Stevens, Christine, Pirinen, Matti, Haritunians, Talin, Neale, Benjamin, Kurki, Mitja, Ganna, Andrea, Graham, Daniel, Glaser, Benjamin, Peter, Inga, Atzmon, Gil, Barzilai, Nir, Levine, Adam, Schiff, Elena, Pontikos, Nikolas, Weisburd, Ben, Lek, Monkol, Karczewski, Konrad, Bloom, Jonathan, Minikel, Eric, Petersen, Britt-Sabina, Beaugerie, Laurent, Seksik, Philippe, Cosnes, Jacques, Schreiber, Stefan, Bokemeyer, Bernd, Bethge, Johannes, Heap, Graham, Ahmad, Tariq, Plagnol, Vincent, Segal, Anthony, Targan, Stephan, Turner, Dan, Saavalainen, Paivi, Farkkila, Martti, Kontula, Kimmo, Palotie, Aarno, Brant, Steven, Duerr, Richard, Silverberg, Mark, Rioux, John, Weersma, Rinse, Franke, Andre, Jostins, Luke, Anderson, Carl, Barrett, Jeffrey, MacArthur, Daniel, Jalas, Chaim, Sokol, Harry, Xavier, Ramnik, Pulver, Ann, Cho, Judy, McGovern, Dermot, and Daly, Mark
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Algorithms ,Crohn Disease ,Genetic Predisposition to Disease ,Genetics ,Population ,Genome-Wide Association Study ,Haplotypes ,Humans ,Jews ,Models ,Genetic ,Molecular Epidemiology ,Polymorphism ,Single Nucleotide ,Rare Diseases - Abstract
As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at https://ibd.broadinstitute.org, also available in gnomAD at http://gnomad.broadinstitute.org). We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with pathogenic ClinVar alleles (table available at https://github.com/macarthur-lab/clinvar/blob/master/output/clinvar.tsv), including those that account for 10-100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p.Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohns disease, a common disease with an estimated two to four-fold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect-size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohns disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p < 0.005), including several novel contributing alleles, show evidence of association to CD. Independently, we find that genomewide common variant risk defined by GWAS shows a strong difference between AJ and non-AJ European control population samples (0.97 s.d. higher, p
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- 2018
17. Functional variants in the LRRK2 gene confer shared effects on risk for Crohns disease and Parkinsons disease.
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Hui, Ken, Fernandez-Hernandez, Heriberto, Hu, Jianzhong, Schaffner, Adam, Pankratz, Nathan, Hsu, Nai-Yun, Chuang, Ling-Shiang, Carmi, Shai, Villaverde, Nicole, Li, Xianting, Rivas, Manual, Levine, Adam, Bao, Xiuliang, Labrias, Philippe, Haritunians, Talin, Ruane, Darren, Gettler, Kyle, Chen, Ernie, Li, Dalin, Schiff, Elena, Pontikos, Nikolas, Barzilai, Nir, Brant, Steven, Bressman, Susan, Cheifetz, Adam, Clark, Lorraine, Daly, Mark, Desnick, Robert, Duerr, Richard, Katz, Seymour, Lencz, Todd, Myers, Richard, Ostrer, Harry, Ozelius, Laurie, Payami, Haydeh, Peter, Yakov, Rioux, John, Segal, Anthony, Scott, William, Silverberg, Mark, Vance, Jeffery, Ubarretxena-Belandia, Iban, Foroud, Tatiana, Atzmon, Gil, Peer, Itsik, Ioannou, Yiannis, McGovern, Dermot, Yue, Zhenyu, Schadt, Eric, Cho, Judy, and Peter, Inga
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Alleles ,Autophagy ,Crohn Disease ,Cytoskeleton ,Exome ,Gene Frequency ,Gene Regulatory Networks ,Genetic Loci ,Genetic Predisposition to Disease ,Genetic Variation ,Genome ,Human ,Humans ,Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ,Macrophages ,Odds Ratio ,Open Reading Frames ,Parkinson Disease ,Phenotype ,Reproducibility of Results ,Risk Factors ,Exome Sequencing - Abstract
Crohns disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10-10) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10-8). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinsons disease (PD), and healthy controls revealed extensive pleiotropy, with shared genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant was associated with increased kinase activity, whereas neither N551K nor R1398H variants on the protective haplotype altered kinase activity. We also confirmed that R1398H, but not N551K, increased guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.
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- 2018
18. Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees
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Jun, Goo, Manning, Alisa, Almeida, Marcio, Zawistowski, Matthew, Wood, Andrew R, Teslovich, Tanya M, Fuchsberger, Christian, Feng, Shuang, Cingolani, Pablo, Gaulton, Kyle J, Dyer, Thomas, Blackwell, Thomas W, Chen, Han, Chines, Peter S, Choi, Sungkyoung, Churchhouse, Claire, Fontanillas, Pierre, King, Ryan, Lee, SungYoung, Lincoln, Stephen E, Trubetskoy, Vasily, DePristo, Mark, Fingerlin, Tasha, Grossman, Robert, Grundstad, Jason, Heath, Alison, Kim, Jayoun, Kim, Young Jin, Laramie, Jason, Lee, Jaehoon, Li, Heng, Liu, Xuanyao, Livne, Oren, Locke, Adam E, Maller, Julian, Mazur, Alexander, Morris, Andrew P, Pollin, Toni I, Ragona, Derek, Reich, David, Rivas, Manuel A, Scott, Laura J, Sim, Xueling, Tearle, Rick G, Teo, Yik Ying, Williams, Amy L, Zöllner, Sebastian, Curran, Joanne E, Peralta, Juan, Akolkar, Beena, Bell, Graeme I, Burtt, Noël P, Cox, Nancy J, Florez, Jose C, Hanis, Craig L, McKeon, Catherine, Mohlke, Karen L, Seielstad, Mark, Wilson, James G, Atzmon, Gil, Below, Jennifer E, Dupuis, Josée, Nicolae, Dan L, Lehman, Donna, Park, Taesung, Won, Sungho, Sladek, Robert, Altshuler, David, McCarthy, Mark I, Duggirala, Ravindranath, Boehnke, Michael, Frayling, Timothy M, Abecasis, Gonçalo R, and Blangero, John
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Diabetes ,Genetics ,Human Genome ,Clinical Research ,Obesity ,Genetic Testing ,2.1 Biological and endogenous factors ,Aetiology ,Metabolic and endocrine ,Diabetes Mellitus ,Type 2 ,Family Health ,Female ,Gene Frequency ,Genetic Predisposition to Disease ,Genetic Variation ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Mexican Americans ,Pedigree ,Phenotype ,Quantitative Trait Loci ,Whole Genome Sequencing ,genetics ,sequencing ,type 2 diabetes ,eQTL ,rare variants - Abstract
A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant cis-expression quantitative trait loci that could not be detected in population studies, validating our approach. However, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants.
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- 2018
19. Rare genetic coding variants associated with human longevity and protection against age-related diseases
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Lin, Jhih-Rong, Sin-Chan, Patrick, Napolioni, Valerio, Torres, Guillermo G., Mitra, Joydeep, Zhang, Quanwei, Jabalameli, M. Reza, Wang, Zhen, Nguyen, Nha, Gao, Tina, Laudes, Matthias, Görg, Siegfried, Franke, Andre, Nebel, Almut, Greicius, Michael D., Atzmon, Gil, Ye, Kenny, Gorbunova, Vera, Ladiges, Warren C., Shuldiner, Alan R., Niedernhofer, Laura J., Robbins, Paul D., Milman, Sofiya, Suh, Yousin, Vijg, Jan, Barzilai, Nir, and Zhang, Zhengdong D.
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- 2021
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20. Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology.
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Miller, Brendan, Kim, Su‐Jeong, Cao, Kevin, Mehta, Hemal H., Thumaty, Neehar, Kumagai, Hiroshi, Iida, Tomomitsu, McGill, Cassandra, Pike, Christian J., Nurmakova, Kamila, Levine, Zachary A., Sullivan, Patrick M., Yen, Kelvin, Ertekin‐Taner, Nilüfer, Atzmon, Gil, Barzilai, Nir, and Cohen, Pinchas
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APOLIPOPROTEIN E4 ,APOLIPOPROTEIN E ,BRAIN diseases ,MOLECULAR pathology ,DISEASE risk factors ,PEPTIDES - Abstract
The APOE4 allele is recognized as a significant genetic risk factor to Alzheimer's disease (AD) and influences longevity. Nonetheless, some APOE4 carriers exhibit resistance to AD even in advanced age. Humanin, a mitochondrial‐derived peptide comprising 24 amino acids, has variants linked to cognitive resilience and longevity. Our research uncovered a unique humanin variant, P3S, specifically enriched in centenarians with the APOE4 allele. Through in silico analyses and subsequent experimental validation, we demonstrated a strong affinity between humanin P3S and APOE4. Utilizing an APOE4‐centric mouse model of amyloidosis (APP/PS1/APOE4), we observed that humanin P3S significantly attenuated brain amyloid‐beta accumulation compared to the wild‐type humanin. Transcriptomic assessments of mice treated with humanin P3S highlighted its potential mechanism involving the enhancement of amyloid beta phagocytosis. Additionally, in vitro studies corroborated humanin P3S's efficacy in promoting amyloid‐beta clearance. Notably, in the temporal cortex of APOE4 carriers, humanin expression is correlated with genes associated with phagocytosis. Our findings suggest a role of the rare humanin variant P3S, especially prevalent among individuals of Ashkenazi descent, in mitigating amyloid beta pathology and facilitating phagocytosis in APOE4‐linked amyloidosis, underscoring its significance in longevity and cognitive health among APOE4 carriers. [ABSTRACT FROM AUTHOR]
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- 2024
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21. A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF
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Chuang, Ling-Shiang, Villaverde, Nicole, Hui, Ken Y, Mortha, Arthur, Rahman, Adeeb, Levine, Adam P, Haritunians, Talin, Ng, Sok Meng Evelyn, Zhang, Wei, Hsu, Nai-Yun, Facey, Jody-Ann, Luong, Tramy, Fernandez-Hernandez, Heriberto, Li, Dalin, Rivas, Manuel, Schiff, Elena R, Gusev, Alexander, Schumm, L Phillip, Bowen, Beatrice M, Sharma, Yashoda, Ning, Kaida, Remark, Romain, Gnjatic, Sacha, Legnani, Peter, George, James, Sands, Bruce E, Stempak, Joanne M, Datta, Lisa W, Lipka, Seth, Katz, Seymour, Cheifetz, Adam S, Barzilai, Nir, Pontikos, Nikolas, Abraham, Clara, Dubinsky, Marla J, Targan, Stephan, Taylor, Kent, Rotter, Jerome I, Scherl, Ellen J, Desnick, Robert J, Abreu, Maria T, Zhao, Hongyu, Atzmon, Gil, Pe’er, Itsik, Kugathasan, Subra, Hakonarson, Hakon, McCauley, Jacob L, Lencz, Todd, Darvasi, Ariel, Plagnol, Vincent, Silverberg, Mark S, Muise, Aleixo M, Brant, Steven R, Daly, Mark J, Segal, Anthony W, Duerr, Richard H, Merad, Miriam, McGovern, Dermot PB, Peter, Inga, and Cho, Judy H
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Clinical Research ,Genetics ,Inflammatory Bowel Disease ,Digestive Diseases ,Crohn's Disease ,2.1 Biological and endogenous factors ,Aetiology ,Case-Control Studies ,Crohn Disease ,Cytokine Receptor Common beta Subunit ,Female ,Frameshift Mutation ,Granulocyte-Macrophage Colony-Stimulating Factor ,Humans ,Intestines ,Jews ,Male ,Monocytes ,Risk Factors ,Signal Transduction ,IBD ,Risk Factor ,Ethnic Variation ,Clinical Sciences ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology - Abstract
Background & aimsCrohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects.MethodsWe performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony-stimulating factor 2-receptor β common subunit gene (CSF2RB). Intestinal tissues and blood samples were collected from patients with CD; lamina propria leukocytes were isolated and expression of CSF2RB and granulocyte-macrophage colony-stimulating factor-responsive cells were defined by adenomatous polyposis coli (APC) time-of-flight mass cytometry (CyTOF analysis). Variants of CSF2RB were transfected into HEK293 cells and the expression and functions of gene products were compared.ResultsIn the discovery cohort, we associated CD with a frameshift mutation in CSF2RB (P = 8.52 × 10(-4)); the finding was validated in the replication cohort (combined P = 3.42 × 10(-6)). Incubation of intestinal lamina propria leukocytes with granulocyte-macrophage colony-stimulating factor resulted in high levels of phosphorylation of signal transducer and activator of transcription (STAT5) and lesser increases in phosphorylation of extracellular signal-regulated kinase and AK straining transforming (AKT). Cells co-transfected with full-length and mutant forms of CSF2RB had reduced pSTAT5 after stimulation with granulocyte-macrophage colony-stimulating factor, compared with cells transfected with control CSF2RB, indicating a dominant-negative effect of the mutant gene. Monocytes from patients with CD who were heterozygous for the frameshift mutation (6% of CD cases analyzed) had reduced responses to granulocyte-macrophage colony-stimulating factor and markedly decreased activity of aldehyde dehydrogenase; activity of this enzyme has been associated with immune tolerance.ConclusionsIn a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with CD.
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- 2016
22. GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.
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Matteini, Amy M, Tanaka, Toshiko, Karasik, David, Atzmon, Gil, Chou, Wen-Chi, Eicher, John D, Johnson, Andrew D, Arnold, Alice M, Callisaya, Michele L, Davies, Gail, Evans, Daniel S, Holtfreter, Birte, Lohman, Kurt, Lunetta, Kathryn L, Mangino, Massimo, Smith, Albert V, Smith, Jennifer A, Teumer, Alexander, Yu, Lei, Arking, Dan E, Buchman, Aron S, Chibinik, Lori B, De Jager, Philip L, Evans, Denis A, Faul, Jessica D, Garcia, Melissa E, Gillham-Nasenya, Irina, Gudnason, Vilmundur, Hofman, Albert, Hsu, Yi-Hsiang, Ittermann, Till, Lahousse, Lies, Liewald, David C, Liu, Yongmei, Lopez, Lorna, Rivadeneira, Fernando, Rotter, Jerome I, Siggeirsdottir, Kristin, Starr, John M, Thomson, Russell, Tranah, Gregory J, Uitterlinden, André G, Völker, Uwe, Völzke, Henry, Weir, David R, Yaffe, Kristine, Zhao, Wei, Zhuang, Wei Vivian, Zmuda, Joseph M, Bennett, David A, Cummings, Steven R, Deary, Ian J, Ferrucci, Luigi, Harris, Tamara B, Kardia, Sharon LR, Kocher, Thomas, Kritchevsky, Stephen B, Psaty, Bruce M, Seshadri, Sudha, Spector, Timothy D, Srikanth, Velandai K, Windham, B Gwen, Zillikens, M Carola, Newman, Anne B, Walston, Jeremy D, Kiel, Douglas P, and Murabito, Joanne M
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Humans ,Hand Strength ,Cohort Studies ,Reproducibility of Results ,Chromatin Immunoprecipitation ,Epigenesis ,Genetic ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Adult ,Aged ,Muscle Strength ,Genome-Wide Association Study ,Molecular Sequence Annotation ,SNP ,aging ,genomewide association ,meta-analysis ,muscle strength ,older adults ,Epigenesis ,Genetic ,Polymorphism ,Single Nucleotide ,Developmental Biology ,Medical and Health Sciences ,Biological Sciences - Abstract
Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10(-8) ) and 39 suggestive (P-value< 5 × 10(-5) ) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10(-10) ). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.
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- 2016
23. Polygenic prediction of human longevity on the supposition of pervasive pleiotropy
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Jabalameli, M.Reza, primary, Lin, Jhih-Rong, additional, Zhang, Quanwei, additional, Wang, Zhen, additional, Mitra, Joydeep, additional, Nguyen, Nha, additional, Gao, Tina, additional, Khusidman, Mark, additional, Atzmon, Gil, additional, Milman, Sofiya, additional, Vijg, Jan, additional, Barzilai, Nir, additional, and Zhang, Zhengdong D., additional
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- 2023
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24. Publisher Correction: A meta-analysis of genome-wide association studies identifies multiple longevity genes
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Deelen, Joris, Evans, Daniel S., Arking, Dan E., Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K., Biggs, Mary L., van der Spek, Ashley, Atzmon, Gil, Ware, Erin B., Sarnowski, Chloé, Smith, Albert V., Seppälä, Ilkka, Cordell, Heather J., Dose, Janina, Amin, Najaf, Arnold, Alice M., Ayers, Kristin L., Barzilai, Nir, Becker, Elizabeth J., Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C., Cubaynes, Sarah, Cummings, Steven R., Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D., Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B., Huisman, Martijn, Hurme, Mikko A., Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon L. R., Kingston, Andrew, Kirkwood, Thomas B. L., Launer, Lenore J., Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B., Nie, Chao, Nohr, Ellen A., Orwoll, Eric S., Perls, Thomas T., Province, Michael A., Psaty, Bruce M., Raitakari, Olli T., Reinders, Marcel J. T., Robine, Jean-Marie, Rotter, Jerome I., Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild I. A., Taylor, Kent D., Uitterlinden, André G., van der Flier, Wiesje, van der Lee, Sven J., van Duijn, Cornelia M., van Heemst, Diana, Vaupel, James W., Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P., Lunetta, Kathryn L., Slagboom, P. Eline, and Murabito, Joanne M.
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- 2021
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25. Identification of Genes Promoting Skin Youthfulness by Genome-Wide Association Study
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Chang, Anne LS, Atzmon, Gil, Bergman, Aviv, Brugmann, Samantha, Atwood, Scott X, Chang, Howard Y, and Barzilai, Nir
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Biomedical and Clinical Sciences ,Clinical Sciences ,Biotechnology ,Aging ,Genetics ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Aged ,Aged ,80 and over ,Animals ,Carrier Proteins ,Face ,Female ,Formins ,Genome-Wide Association Study ,Genotype ,Humans ,Jews ,Langerhans Cells ,Linear Models ,Linkage Disequilibrium ,Male ,Membrane Proteins ,Middle Aged ,Phenotype ,Polymorphism ,Single Nucleotide ,Shal Potassium Channels ,Skin Aging ,Oncology and Carcinogenesis ,Dermatology & Venereal Diseases ,Clinical sciences - Abstract
To identify genes that promote facial skin youthfulness (SY), a genome-wide association study on an Ashkenazi Jewish discovery group (n=428) was performed using Affymetrix 6.0 Single-Nucleotide Polymorphism (SNP) Array. After SNP quality controls, 901,470 SNPs remained for analysis. The eigenstrat method showed no stratification. Cases and controls were identified by global facial skin aging severity including intrinsic and extrinsic parameters. Linear regression adjusted for age and gender, with no significant differences in smoking history, body mass index, menopausal status, or personal or family history of centenarians. Six SNPs met the Bonferroni threshold with Pallele
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- 2014
26. The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function
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Falah, Ghadeer, primary, Sharvit, Lital, additional, and Atzmon, Gil, additional
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- 2023
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27. Copy number variation as a tool for implementing pregnancy as an aging model
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Andrawus, Mariana, primary, Sharvit, Lital, additional, Touitou, Noga, additional, Lerrer, Batia, additional, Cohen, Haim Y., additional, and Atzmon, Gil, additional
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- 2023
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28. Targeted sequencing of the 9p21.3 region reveals association with reduced disease risks in Ashkenazi Jewish centenarians
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Zhu, Yizhou, primary, Ryu, Seungjin, additional, Tare, Archana, additional, Barzilai, Nir, additional, Atzmon, Gil, additional, and Suh, Yousin, additional
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- 2023
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29. Effect of Exceptional Parental Longevity and Lifestyle Factors on Prevalence of Cardiovascular Disease in Offspring
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Gubbi, Sriram, Schwartz, Elianna, Crandall, Jill, Verghese, Joe, Holtzer, Roee, Atzmon, Gil, Braunstein, Rebecca, Barzilai, Nir, and Milman, Sofiya
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- 2017
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30. The history of African gene flow into Southern Europeans, Levantines, and Jews.
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Moorjani, Priya, Patterson, Nick, Hirschhorn, Joel, Keinan, Alon, Hao, Li, Atzmon, Gil, Burns, Edward, Ostrer, Harry, Price, Alkes, and Reich, David
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African Continental Ancestry Group ,Asian Continental Ancestry Group ,Chromosomes ,Emigration and Immigration ,Ethnic Groups ,European Continental Ancestry Group ,Gene Flow ,Gene Pool ,Genetic Variation ,Genetics ,Population ,Genome ,Human ,Haplotypes ,Humans ,Jews ,Polymorphism ,Single Nucleotide - Abstract
Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%-3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%-15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%-5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas.
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- 2011
31. Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults.
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Walston, Jeremy D, Matteini, Amy M, Nievergelt, Caroline, Lange, Leslie A, Fallin, Dani M, Barzilai, Nir, Ziv, Elad, Pawlikowska, Ludmila, Kwok, Pui, Cummings, Steve R, Kooperberg, Charles, LaCroix, Andrea, Tracy, Russell P, Atzmon, Gil, Lange, Ethan M, and Reiner, Alex P
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Humans ,Cardiovascular Diseases ,Inflammation ,Poly(ADP-ribose) Polymerases ,Interleukin-6 ,Risk Factors ,Case-Control Studies ,Aging ,Longevity ,Genotype ,Phenotype ,Aged ,Aged ,80 and over ,Female ,Male ,Genetic Variation ,Poly (ADP-Ribose) Polymerase-1 ,IL-6 ,PARP1 ,Genetic epidemiology ,Clinical Research ,Genetics ,2.1 Biological and endogenous factors ,Cardiovascular ,Inflammatory and immune system ,Gerontology ,Medical and Health Sciences - Abstract
Interleukin-6 (IL-6) is an inflammatory cytokine that influences the development of inflammatory and aging-related disorders and ultimately longevity. In order to study the influence of variants in genes that regulate inflammatory response on IL-6 levels and longevity, we screened a panel of 477 tag SNPs across 87 candidate genes in >5000 older participants from the population-based Cardiovascular Health Study (CHS). Baseline plasma IL-6 concentration was first confirmed as a strong predictor of all-cause mortality. Functional alleles of the IL6R and PARP1 genes were significantly associated with 15%-20% higher baseline IL-6 concentration per copy among CHS European-American (EA) participants (all p
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- 2009
32. The regulation of Insulin/IGF-1 signaling by miR-142-3p associated with human longevity
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Wang, Xifan, primary, Jung, Hwa Jin, additional, Milholland, Brandon, additional, Cui, Jinhua, additional, Tazearslan, Cagdas, additional, Atzmon, Gil, additional, Wang, Xizhe, additional, Yang, Jiping, additional, Guo, Qinghua, additional, Barzilai, Nir, additional, Robbins, Paul D, additional, and Suh, Yousin, additional
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- 2023
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33. Longevity-associated SMAD3 non-coding centenarian variant impairs a cell-type specific enhancer to reduce inflammation
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Yang, Jiping, primary, Tare, Archana, additional, Zhang, Lei, additional, Kim, Seungsoo, additional, Ryu, Seungjin, additional, Guo, Qinghua, additional, Zhu, Yizhou, additional, Wang, Xizhe, additional, Wang, Xifan, additional, Hudgins, Adam D, additional, Guan, Di, additional, Jin, Chen, additional, Chang, Hyun-Kyung, additional, Atzmon, Gil, additional, Milman, Sofiya, additional, Barzilai, Nir, additional, Vijg, Jan, additional, Niedernhofer, Laura, additional, Robbins, Paul D, additional, and Suh, Yousin, additional
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- 2023
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34. Empirical design of a variant quality control pipeline for whole genome sequencing data using replicate discordance
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Adelson, Robert P., Renton, Alan E., Li, Wentian, Barzilai, Nir, Atzmon, Gil, Goate, Alison M., Davies, Peter, and Freudenberg-Hua, Yun
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- 2019
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35. Genomics of Aging and Longevity
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Falah, Ghadeer, primary, Gutman, Danielle, additional, and Atzmon, Gil, additional
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- 2019
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36. Genomic and Epigenomic Potential With Age: Genome, Epigenome, and the Epigenetic Clock
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Gutman, Danielle, primary and Atzmon, Gil, additional
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- 2019
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37. Contributors
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Ait-Si-Ali, Slimane, primary, Albini, Sonia, additional, Atzmon, Gil, additional, Badylak, Stephen F., additional, Barnstable, C.J., additional, Biferali, Beatrice, additional, Caporale, Nicolò, additional, Chen, Zhaoyi, additional, Chiacchiera, Fulvio, additional, Coffman, James A., additional, D’Angelo, William, additional, Dean, Wendy, additional, Eriksson, Jonas, additional, Fernández, Agustín F., additional, Fraga, Mario F., additional, Guil, Sònia, additional, Gutman, Danielle, additional, Hadi, Nur Annies Abd, additional, Hanna, Courtney W., additional, Josipović, Nataša, additional, Julian, Lisa M., additional, Mai, Antonello, additional, Marelli, Luca, additional, McCarthy, Ryan L., additional, McLaughlin, Katy A., additional, Meehan, Richard R., additional, Mozzetta, Chiara, additional, Nicetto, Dario, additional, Oliveira-Mateos, Cristina, additional, Ottaviano, Raffaele, additional, Pagiatakis, Christina, additional, Palacios, Daniela, additional, Papait, Roberto, additional, Papantonis, Argyris, additional, Pennings, Sari, additional, Pérez, Raúl F., additional, Petchreing, Petchroi, additional, Pietrobon, Adam, additional, Popova, E.Y., additional, Revuelta, Ailsa, additional, Sánchez-Castillo, Anaís, additional, Santamarina, Pablo, additional, Serio, Simone, additional, Stanford, William L., additional, Stazi, Giulia, additional, Testa, Giuseppe, additional, Valente, Sergio, additional, Viscomi, Maria Teresa, additional, Zakharova, Vlada, additional, Zaret, Kenneth S., additional, and Zwergel, Clemens, additional
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- 2019
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38. High-depth whole genome sequencing of an Ashkenazi Jewish reference panel: enhancing sensitivity, accuracy, and imputation
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Lencz, Todd, Yu, Jin, Palmer, Cameron, Carmi, Shai, Ben-Avraham, Danny, Barzilai, Nir, Bressman, Susan, Darvasi, Ariel, Cho, Judy H., Clark, Lorraine N., Gümüş, Zeynep H., Joseph, Vijai, Klein, Robert, Lipkin, Steven, Offit, Kenneth, Ostrer, Harry, Ozelius, Laurie J., Peter, Inga, Atzmon, Gil, and Pe’er, Itsik
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- 2018
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39. Greater effect of polygenic risk score for Alzheimer's disease among younger cases who are apolipoprotein E-ε4 carriers
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Fulton-Howard, Brian, Goate, Alison M., Adelson, Robert P., Koppel, Jeremy, Gordon, Marc L., Barzilai, Nir, Atzmon, Gil, Davies, Peter, and Freudenberg-Hua, Yun
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- 2021
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40. Can Epigenetics Predict Drug Efficiency in Mental Disorders?
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Ben David, Gil, primary, Amir, Yam, additional, Salalha, Randa, additional, Sharvit, Lital, additional, Richter-Levin, Gal, additional, and Atzmon, Gil, additional
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- 2023
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41. Perspective on This Article from Abdominal Obesity, Independent from Caloric Intake, Accounts for the Development of Intestinal Tumors in Apc1638N/+ Female Mice
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Huffman, Derek M., primary, Augenlicht, Leonard H., primary, Zhang, Xueying, primary, Lofrese, John J., primary, Atzmon, Gil, primary, Chamberland, John P., primary, and Mantzoros, Christos S., primary
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- 2023
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42. Data from Abdominal Obesity, Independent from Caloric Intake, Accounts for the Development of Intestinal Tumors in Apc1638N/+ Female Mice
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Huffman, Derek M., primary, Augenlicht, Leonard H., primary, Zhang, Xueying, primary, Lofrese, John J., primary, Atzmon, Gil, primary, Chamberland, John P., primary, and Mantzoros, Christos S., primary
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- 2023
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43. Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity
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Adwan Shekhidem, Huda, primary, Sharvit, Lital, additional, Huffman, Derek M., additional, Manov, Irena, additional, Atzmon, Gil, additional, and Shams, Imad, additional
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- 2023
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44. Exposure to Juvenile Stress Induces Epigenetic Alterations in the GABAergic System in Rats
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Ben David, Gil, primary, Amir, Yam, additional, Tripathi, Kuldeep, additional, Sharvit, Lital, additional, Benhos, Amir, additional, Anunu, Rachel, additional, Richter-Levin, Gal, additional, and Atzmon, Gil, additional
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- 2023
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45. A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A
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Simon, Matthew, primary, Yang, Jiping, additional, Gigas, Jonathan, additional, Earley, Eric J, additional, Hillpot, Eric, additional, Zhang, Lei, additional, Zagorulya, Maria, additional, Tombline, Greg, additional, Gilbert, Michael, additional, Yuen, Samantha L, additional, Pope, Alexis, additional, Van Meter, Michael, additional, Emmrich, Stephan, additional, Firsanov, Denis, additional, Athreya, Advait, additional, Biashad, Seyed Ali, additional, Han, Jeehae, additional, Ryu, Seungjin, additional, Tare, Archana, additional, Zhu, Yizhou, additional, Hudgins, Adam, additional, Atzmon, Gil, additional, Barzilai, Nir, additional, Wolfe, Aaron, additional, Moody, Kelsey, additional, Garcia, Benjamin A, additional, Robbins, Paul D, additional, Vijg, Jan, additional, Seluanov, Andrei, additional, Suh, Yousin, additional, and Gorbunova, Vera, additional
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- 2023
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46. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome
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Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle C., Boomsma, Dorret I., Roessner, Veit, Wolanczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya-Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Munchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, Dietrich, Andrea, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., Paschou, Peristera, Als, Thomas D., Aschauer, Harald, Atzmon, Gil, Bækvad-Hansen, Matie, Barr, Cathy L., Barzilai, Nir, Batterson, James R., Batterson, Robert, Benarroch, Fortu, Berlin, Cheston, Boberg, Julia, Bodmer, Benjamin, Bohnenpoll, Julia, Børglum, Anders D., Brown, Lawrence W., Bruun, Ruth, Budman, Cathy L., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cheon, Keun-Ah, Chouinard, Sylvain, Coffey, Barbara J., Coppola, Giovanni, Crowley, James J., Dahl, Niklas, Darrow, Sabrina M., Daly, Mark J., De Rubeis, Silvia, Dion, Yves, Djurfeldt, Diana R., Domenech-Salgado, Laura, Eapen, Valsamma, Elzerman, Lonneke, Fernandez, Thomas V., Freimer Carolin Fremer, Nelson B., Garcia-Delgar, Blanca, Garrido, Marcos, Gilbert, Donald L., Giusti-Rodriguez, Paola, Grados, Marco, Greenberg, Erica, Grove, Jakob, Hagstrom, Julie, Halvorsen, Matt, Hansen, Bjarne, Haavik, Jan, Hebebrand, Johannes, Heiman, Gary A., Herrera, Luis, Hinney, Anke, Hirschtritt, Matthew E., Sul, Jae Hoon, Hong, Hyun Ju, Hougaard, David M., Huang, Alden Y., Ibanez-Gomez, Laura, Ivankovic, Franjo, Jankovic, Joseph, Karlsson, Elinor K., Kaprio, Jakko A., Kim, Young Key, Kim, Young-Shin, King, Robert A., Knowles, James A., Koh, Yun-Joo, Kook, Sodham, Khalifa, Najah, Konstantinidis, Anastasios, Kuperman, Samuel, Kurlan, Roger, Kvale, Gerd, Leckman, James, Lee, Paul C., Leventhal, Bennett, Lichtenstein, Paul, Lindbald-Toh, Kerstin, Lowe, Thomas, Ludolph, Andrea, da Silva, Claudia Luhrs, Luðvigsson, Pétur, Luykx, Jurjen, Lyon, Gholson J., Mahjani, Behrang, Maras, Athanasios, Mataix-Cols, David, Mattheisen, Manuel, Malaty, Irene A., McMahon, William M., McQuillin, Andrew, Meier, Sandra M., Moessner, Rainald, Mortensen, Preben B., Mors, Ole, Mudgal, Poorva, Nagy, Peter, Naarden, Allan, Neale, Benjamin M., Nawaz, Muhammad S., Nissen, Judith Becker, Nöthen Merete Nordentoft, Markus M., Nordsletten, Ashley E., Okun, Michael S., Ophoff, Roel, Osiecki, Lisa, Palotie, Aarno, Palviainen, Teemu P., Pato Michele T. Pato, Carlos N., Pittenger, Christopher, Pollak, Yehuda, Posthuma, Danielle, Ramos, Eliana, Reichert, Jennifer, Robertson, Mary M., Roffman, Joshua L., Rouleau, Guy, Rück, Christian, Sæmundsen, Evald, Samuels, Jack, Sandin, Sven, Sandor, Paul, Schlögelhofer, Monika, Shin, Eun-Young, Singer, Harvey S., Smit, Jan, Smoller, Jordan W., State, Matthew, Solem, Stian, Song, Dong-Ho, Song, Jungeun, Stamenkovic, Mara, Stefansson, Kári, Strom, Nora, Stuhrmann, Manfred, Szatkiewicz, Jin, Szymanska, Urszula, Tischfield, Jay A., Tsetsos, Fotis, Thorarensen, Ólafur, Tubing, Jennifer, Visscher, Frank, Wagner, Michael, Wanderer, Sina, Wang, Sheng, Werge, Thomas, Willsey, Jeremy A., Wolancyk, Tomasz, Woods, Douglas W., Woods, Martin, Zelaya, Ivette, Zinner, Samuel H., Apter, Alan, Ball, Juliane, Bognar, Emese, Buse, Judith, Vela, Marta Correa, Fremer, Carolin, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Madruga-Garrido, Marcos, Pellico, Alessandra, Ruhrman, Daphna, Schnell, Jaana, Silvestri, Paola Rosaria, Skov, Liselotte, Steinberg, Tamar, Gloor, Friederike Tagwerker, Turner, Victoria L., Weidinger, Elif, Alexander, John, Aranyi, Tamas, Buisman, Wim R., Buitelaar, Jan K., Driessen, Nicole, Fan, Siyan, Forde, Natalie J., Gerasch, Sarah, van den Heuvel, Odile A., Jespersgaard, Cathrine, Kanaan, Ahmad S., Möller, Harald E., Nespoli, Ester, Pagliaroli, Luca, Poelmans, Geert, Pouwels, Petra J. W., Rizzo, Francesca, Veltman, Dick J., van der Werf, Ysbrand D., Widomska, Joanna, Zilhäo, Nuno R., Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Dynamic Earth and Resources, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
- Subjects
Male ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Medizin ,Autism Spectrum Disorder/genetics ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Diabetes Mellitus, Type 2 ,Risk Factors ,Diabetes Mellitus ,Tourette Syndrome/genetics ,Humans ,Female ,Attention Deficit Disorder with Hyperactivity/genetics ,Type 2 ,Biological Psychiatry - Abstract
Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders. Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.
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- 2023
47. The Epigenetic Regulation of Telomere Maintenance in Aging
- Author
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Adwan-Shekhidem, Huda, primary and Atzmon, Gil, additional
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- 2018
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48. List of Contributors
- Author
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Abdel-Rahman, Emaad M., primary, Ackerman, Hayley D., additional, Akintola, Abimbola, additional, Amdam, Gro V., additional, Atzmon, Gil, additional, Austad, Steve, additional, Awate, Sanket, additional, Balaskó, Márta, additional, Banerjee, Taraswi, additional, Bárcena, Clea, additional, Bartke, Andrzej, additional, Bassi, Ivan, additional, Berendt, Mette, additional, Bijlsma, Maarten F., additional, Bitto, Alessandro, additional, Bizon, Jennifer L., additional, Bollaerts, Ilse, additional, Bonomi, Marco, additional, Borras, Consuelo, additional, Bowman, Brendan T., additional, Brioche, Thomas, additional, Brosh, Robert M., additional, Brown, Richard E., additional, Buck, Kerstin, additional, Burke, Sara N., additional, Buzgariu, Wanda, additional, Cacabelos, Ramón, additional, Camina Martín, M.A., additional, Chaffee, Beth K., additional, Chan, Anthony W.S., additional, Chen, Haolin, additional, Chen, Zhiguo, additional, Cho, In K., additional, Chopard, Angèle, additional, Cogger, Victoria C., additional, Cohen, Alan A., additional, Confino, Rafael, additional, Coppedè, Fabio, additional, Costa, Anthony J., additional, Crouch, Jack D., additional, Darcy, Justin, additional, De Groef, Lies, additional, de Mateo Silleras, B., additional, Deepa, Sathyaseelan S., additional, Devau, Gina, additional, Dhenain, Marc, additional, Dills, Chantelle, additional, Duffy, Megan F., additional, Duncan, Francesca E., additional, Dupuis, Gilles, additional, Eaton, Benjamin A., additional, Egan, Josephine M., additional, Ekundayo, Kazadi, additional, Emborg, Marina E., additional, Fischer, D. Luke, additional, Fontes, Pascaline, additional, Fortepiani, Maria Lourdes Alarcon, additional, Fortin, Carl, additional, Franzke, Bernhard, additional, Fülöp, Tamas, additional, Gabriel, Camelia, additional, Galliot, Brigitte, additional, Gambini, Juan, additional, Garneau, Hugo, additional, Gasparini, Laura, additional, Gerhard, Glenn S., additional, Gibson, David C., additional, Gimeno-Mallench, Lucia, additional, Girard, Victor, additional, Greer, Kimberly A., additional, Gribble, Kristin E., additional, Gubbels Bupp, Melanie R., additional, Gudmundsson, Adalsteinn, additional, Hamann, Andrea, additional, Hamblin, Michael R., additional, Harper, James M., additional, Hart, Ronald, additional, Head, Elizabeth, additional, Herd, Heather R., additional, Herrera, Guadalupe, additional, Hisama, Fuki M., additional, Hogan, David B., additional, Holmes, Donna J., additional, Hornsby, Peter J., additional, Howlett, Susan E., additional, Hui, Ka Yi, additional, Jahn, Thomas R., additional, Jávega, Beatriz, additional, Jeffery, William R., additional, Johnson, Sarah A., additional, Jones, Audrey, additional, Jones, Corinne A., additional, Jónsson, Pálmi V., additional, Kane, Alice E., additional, Karasik, David, additional, Kean, Samuel, additional, Keller, Evan T., additional, Keller, Jill M., additional, Kemp, Christopher J., additional, Wong, Ken S.K., additional, Krøll, Jens, additional, Kumar Bharti, Sanjay, additional, Kurkinen, Markku, additional, Larbi, Anis, additional, Lasbleiz, Christelle, additional, Lautier, Corinne, additional, Le Couteur, David G., additional, Le Page, Aurelie, additional, Lin, Hang, additional, López-Otín, Carlos, additional, Lottonen-Raikaslehto, Line, additional, Magden, Elizabeth R., additional, Makrantonaki, Evgenia, additional, Manfredsson, Fredric P., additional, Mark Welch, David B., additional, Marques-Lopes, Jose, additional, Martínez-Romero, Alicia, additional, Mas-Bargues, Cristina, additional, Mayoral, Pablo, additional, Mc Auley, Mark, additional, McQuail, Joseph A., additional, Merentie, Mari, additional, Mestre-Frances, Nadine, additional, Metzger, Jeanette M., additional, Meyer, Keith C., additional, Milner, Teresa A., additional, Mizutani, Claudia M., additional, Monnat, Raymond J., additional, Mooney, Kathleen, additional, Moons, Lieve, additional, Muck, Joscha, additional, Muniyappa, Ranganath, additional, Nehlin, Jan O., additional, Neubauer, Oliver, additional, Nikolakis, Georgios, additional, Nyman, Jeffry S., additional, O’Connor, José-Enrique, additional, Oshima, Junko, additional, Osiewacz, Heinz D., additional, Papadopoulos, Vassilios, additional, Pavone, Mary Ellen, additional, Pawelec, Graham, additional, Pedersen, Jan T., additional, Perez-Lopez, Gonzalo, additional, Persani, Luca, additional, Pétervári, Erika, additional, Peyman, Azadeh, additional, Plate, Johannes F., additional, Polinski, Nicole K., additional, Py, Guillaume, additional, Quigley, Tyler P., additional, Rae, Eric A., additional, Ram, Jeffrey L., additional, Raubenheimer, David, additional, Reckelhoff, Jane F., additional, Redondo del Río, M.P., additional, Rex-Al Panem Orbon, Jovy, additional, Richardson, Arlan, additional, Ripperger, Jürgen A., additional, Rostás, Ildikó, additional, Rouse, Michael, additional, Rueppell, Olav, additional, Runge, Kurt W., additional, Safdar, Maryam, additional, Sankaran-Walters, Sumathi, additional, Santago, Anthony C., additional, Sarvimäki, Anneli, additional, Saul, Katherine R., additional, Schenkelaars, Quentin, additional, Schneider, Brandt L., additional, Schütt, Trine, additional, Shen, He, additional, Shin, Sooyoun, additional, Simpson, Stephen J., additional, Smith, Jessica, additional, Snell, Terry W., additional, Snyder, Jessica M., additional, Solon-Biet, Samantha M., additional, Soós, Szilvia, additional, Sortwell, Caryl E., additional, Sousa-Neves, Rui, additional, Steece-Collier, Kathy, additional, Steins, Anne, additional, Sujkowski, Alyson, additional, Swanberg, Susan E., additional, Teijido, Oscar, additional, Tella, Sri Harsha, additional, Tenk, Judit, additional, Tomczyk, Szymon, additional, Treuting, Piper M., additional, Trouche, Stéphanie G., additional, Tuan, Rocky S., additional, Unnikrishnan, Archana, additional, Valenzano, Dario Riccardo, additional, van Heemst, Diana, additional, Van houcke, Jessie, additional, Van Kempen, Tracey A., additional, van Laarhoven, Hanneke W.M., additional, Verdier, Jean-Michel, additional, Viña, Jose, additional, Wagner, Karl-Heinz, additional, Wahl, Devin, additional, Wenger, Yvan, additional, Wessells, Robert J., additional, Wilcock, Donna M., additional, Witkowski, Jacek M., additional, Wong, Esther, additional, Woodland, Nicole, additional, Yanes Cardozo, Licy L., additional, Ylä-Herttuala, Seppo, additional, Youssef, Sameh A., additional, Yuan, Rong, additional, Zhang, Haitao, additional, Zhou, Zhongjun, additional, Zirkin, Barry R., additional, and Zouboulis, Christos C., additional
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- 2018
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49. Genetics of Human Aging
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Atzmon, Gil, primary and Karasik, David, additional
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- 2018
- Full Text
- View/download PDF
50. List of Contributors
- Author
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Adwan-Shekhidem, Huda, primary, Atzmon, Gil, additional, Benayoun, Bérénice A., additional, Bowman, John D., additional, Braun, Kim V.E., additional, Cacabelos, Ramón, additional, Caiafa, Paola, additional, Cao, Xiaohua, additional, Choudhury, Mahua, additional, Chowdhury, Rajiv, additional, Ciccarone, Fabio, additional, Cunliffe, Vincent T., additional, Dang, Weiwei, additional, Dong, Xiao, additional, Eachus, Helen, additional, Franco, Oscar H., additional, Gravina, Silvia, additional, Koliada, Alexander K., additional, Kovalchuk, Igor, additional, Kranjc, Tilen, additional, Kudryavtseva, Anna, additional, Kumar, Vineet, additional, Langley-Evans, Simon C., additional, Loenen, Wil A.M., additional, Lovšin, Nika, additional, Lushchak, Oleh V., additional, Marc, Janja, additional, Meruvu, Sunitha, additional, Mills, Ken I., additional, Mitnitski, Arnold B., additional, Moskalev, Alexey, additional, Muhlhausler, Beverly S., additional, Muka, Taulant, additional, Nano, Jana, additional, O’Sullivan, Justin M., additional, Ostanek, Barbara, additional, Portilla, Eliana, additional, Raj, Ken, additional, Rea, Irene M., additional, Reynolds, Clare M., additional, Schumacher, Axel, additional, Seaborne, Robert A., additional, Segovia, Stephanie A., additional, Shaposhnikov, Mikhail, additional, Sharples, Adam P., additional, Solovev, Ilya, additional, Stewart, Claire E., additional, Teijido, Oscar, additional, Troup, Jenna, additional, Ucar, Duygu, additional, Vaiserman, Alexander M., additional, Verma, Mukesh, additional, Vickers, Mark H., additional, Vijg, Jan, additional, Voortman, Trudy, additional, Xu, Xiangru, additional, Zampieri, Michele, additional, and Zupan, Janja, additional
- Published
- 2018
- Full Text
- View/download PDF
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