Medicine and Health Sciences Commons^™

Mosaic Chromosomal Alterations In Blood Across Ancestries Using Whole-Genome Sequencing, Yasminka A Jakubek, Ying Zhou, Adrienne Stilp, Jason Bacon, Justin W Wong, Zuhal Ozcan, Donna Arnett, Kathleen Barnes, Joshua C Bis, Eric Boerwinkle, Jennifer A Brody, April P Carson, Daniel I Chasman, Jiawen Chen, Michael Cho, Matthew P Conomos, Nancy Cox, Margaret F Doyle, Myriam Fornage, Xiuqing Guo, Sharon L R Kardia, Joshua P Lewis, Ruth J F Loos, Xiaolong Ma, Mitchell J Machiela, Taralynn M Mack, Rasika A Mathias, Braxton D Mitchell, Josyf C Mychaleckyj, Kari North, Nathan Pankratz, Patricia A Peyser, Michael H Preuss, Bruce Psaty, Laura M Raffield, Ramachandran S Vasan, Susan Redline, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Jennifer A Smith, Aaron P Smith, Margaret Taub, Kent D Taylor, Jeong Yun, Yun Li, Pinkal Desai, Alexander G Bick, Alexander P Reiner, Paul Scheet, Paul L Auer

Journal Articles

Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. …

Whole-Genome Sequencing Analysis Of Human Metabolome In Multi-Ethnic Populations, Elena V Feofanova, Michael R Brown, Taryn Alkis, Astrid M Manuel, Xihao Li, Usman A Tahir, Zilin Li, Kevin M Mendez, Rachel S Kelly, Qibin Qi, Han Chen, Martin G Larson, Rozenn N Lemaitre, Alanna C Morrison, Charles Grieser, Kari E Wong, Robert E Gerszten, Zhongming Zhao, Jessica Lasky-Su, Bing Yu

Journal Articles

Circulating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven …

New Insights Into The Genetic Etiology Of Alzheimer's Disease And Related Dementias, Céline Bellenguez, Fahri Küçükali, Iris E Jansen, Luca Kleineidam, Sonia Moreno-Grau, Najaf Amin, Adam C Naj, Rafael Campos-Martin, Benjamin Grenier-Boley, Victor Andrade, Peter A Holmans, Anne Boland, Vincent Damotte, Sven J Van Der Lee, Marcos R Costa, Teemu Kuulasmaa, Qiong Yang, Itziar De Rojas, Joshua C Bis, Amber Yaqub, Ivana Prokic, Julien Chapuis, Shahzad Ahmad, Vilmantas Giedraitis, Dag Aarsland, Pablo Garcia-Gonzalez, Carla Abdelnour, Emilio Alarcón-Martín, Daniel Alcolea, Montserrat Alegret, Ignacio Alvarez, Victoria Álvarez, Nicola J Armstrong, Anthoula Tsolaki, Carmen Antúnez, Ildebrando Appollonio, Marina Arcaro, Silvana Archetti, Alfonso Arias Pastor, Beatrice Arosio, Lavinia Athanasiu, Henri Bailly, Nerisa Banaj, Miquel Baquero, Sandra Barral, Alexa Beiser, Ana Belén Pastor, Jennifer E Below, Penelope Benchek, Luisa Benussi, Claudine Berr, Céline Besse, Valentina Bessi, Giuliano Binetti, Alessandra Bizarro, Rafael Blesa, Mercè Boada, Eric Boerwinkle, Barbara Borroni, Silvia Boschi, Paola Bossù, Geir Bråthen, Jan Bressler, Catherine Bresner, Henry Brodaty, Keeley J Brookes, Luis Ignacio Brusco, Dolores Buiza-Rueda, Katharina Bûrger, Vanessa Burholt, William S Bush, Miguel Calero, Laura B Cantwell, Geneviève Chene, Jaeyoon Chung, Michael L Cuccaro, Ángel Carracedo, Roberta Cecchetti, Laura Cervera-Carles, Camille Charbonnier, Hung-Hsin Chen, Caterina Chillotti, Simona Ciccone, Jurgen A H R Claassen, Christopher Clark, Elisa Conti, Anaïs Corma-Gómez, Emanuele Costantini, Carlo Custodero, Delphine Daian, Maria Carolina Dalmasso, Antonio Daniele, Efthimios Dardiotis, Jean-François Dartigues, Peter Paul De Deyn, Katia De Paiva Lopes, Lot D De Witte, Stéphanie Debette, Jürgen Deckert, Teodoro Del Ser, Nicola Denning, Anita Destefano, Martin Dichgans, Janine Diehl-Schmid, Mónica Diez-Fairen, Paolo Dionigi Rossi, Srdjan Djurovic, Emmanuelle Duron, Emrah Düzel, Carole Dufouil, Gudny Eiriksdottir, Sebastiaan Engelborghs, Valentina Escott-Price, Ana Espinosa, Michael Ewers, Kelley M Faber, Tagliavini Fabrizio, Sune Fallgaard Nielsen, David W Fardo, Lucia Farotti, Chiara Fenoglio, Marta Fernández-Fuertes, Raffaele Ferrari, Catarina B Ferreira, Evelyn Ferri, Bertrand Fin, Peter Fischer, Tormod Fladby, Klaus Fließbach, Bernard Fongang, Myriam Fornage, Juan Fortea, Tatiana M Foroud, Silvia Fostinelli, Nick C Fox, Emlio Franco-Macías, María J Bullido, Ana Frank-García, Lutz Froelich, Brian Fulton-Howard, Daniela Galimberti, Jose Maria García-Alberca, Pablo García-González, Sebastian Garcia-Madrona, Guillermo Garcia-Ribas, Roberta Ghidoni, Ina Giegling, Giaccone Giorgio, Alison M Goate, Oliver Goldhardt, Duber Gomez-Fonseca, Antonio González-Pérez, Caroline Graff, Giulia Grande, Emma Green, Timo Grimmer, Edna Grünblatt, Michelle Grunin, Vilmundur Gudnason, Tamar Guetta-Baranes, Annakaisa Haapasalo, Georgios Hadjigeorgiou, Jonathan L Haines, Kara L Hamilton-Nelson, Harald Hampel, Olivier Hanon, John Hardy, Annette M Hartmann, Lucrezia Hausner, Janet Harwood, Stefanie Heilmann-Heimbach, Seppo Helisalmi, Michael T Heneka, Isabel Hernández, Martin J Herrmann, Per Hoffmann, Clive Holmes, Henne Holstege, Raquel Huerto Vilas, Marc Hulsman, Jack Humphrey, Geert Jan Biessels, Xueqiu Jian, Charlotte Johansson, Gyungah R Jun, Yuriko Kastumata, John Kauwe, Patrick G Kehoe, Lena Kilander, Anne Kinhult Ståhlbom, Miia Kivipelto, Anne Koivisto, Johannes Kornhuber, Mary H Kosmidis, Walter A Kukull, Pavel P Kuksa, Brian W Kunkle, Amanda B Kuzma, Carmen Lage, Erika J Laukka, Lenore Launer, Alessandra Lauria, Chien-Yueh Lee, Jenni Lehtisalo, Ondrej Lerch, Alberto Lleó, William Longstreth, Oscar Lopez, Adolfo Lopez De Munain, Seth Love, Malin Löwemark, Lauren Luckcuck, Kathryn L Lunetta, Yiyi Ma, Juan Macías, Catherine A Macleod, Wolfgang Maier, Francesca Mangialasche, Marco Spallazzi, Marta Marquié, Rachel Marshall, Eden R Martin, Angel Martín Montes, Carmen Martínez Rodríguez, Carlo Masullo, Richard Mayeux, Simon Mead, Patrizia Mecocci, Miguel Medina, Alun Meggy, Shima Mehrabian, Silvia Mendoza, Manuel Menéndez-González, Pablo Mir, Susanne Moebus, Merel Mol, Laura Molina-Porcel, Laura Montrreal, Laura Morelli, Fermin Moreno, Kevin Morgan, Thomas Mosley, Markus M Nöthen, Carolina Muchnik, Shubhabrata Mukherjee, Benedetta Nacmias, Tiia Ngandu, Gael Nicolas, Børge G Nordestgaard, Robert Olaso, Adelina Orellana, Michela Orsini, Gemma Ortega, Alessandro Padovani, Caffarra Paolo, Goran Papenberg, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Gina Peloso, Alba Pérez-Cordón, Jordi Pérez-Tur, Pierre Pericard, Oliver Peters, Yolande A L Pijnenburg, Juan A Pineda, Gerard Piñol-Ripoll, Claudia Pisanu, Thomas Polak, Julius Popp, Danielle Posthuma, Josef Priller, Raquel Puerta, Olivier Quenez, Inés Quintela, Jesper Qvist Thomassen, Alberto Rábano, Innocenzo Rainero, Farid Rajabli, Inez Ramakers, Luis M Real, Marcel J T Reinders, Christiane Reitz, Dolly Reyes-Dumeyer, Perry Ridge, Steffi Riedel-Heller, Peter Riederer, Natalia Roberto, Eloy Rodriguez-Rodriguez, Arvid Rongve, Irene Rosas Allende, Maitée Rosende-Roca, Jose Luis Royo, Elisa Rubino, Dan Rujescu, María Eugenia Sáez, Paraskevi Sakka, Ingvild Saltvedt, Ángela Sanabria, María Bernal Sánchez-Arjona, Florentino Sanchez-Garcia, Pascual Sánchez Juan, Raquel Sánchez-Valle, Sigrid B Sando, Chloé Sarnowski, Claudia L Satizabal, Michela Scamosci, Nikolaos Scarmeas, Elio Scarpini, Philip Scheltens, Norbert Scherbaum, Martin Scherer, Matthias Schmid, Anja Schneider, Jonathan M Schott, Geir Selbæk, Davide Seripa, Manuel Serrano, Jin Sha, Alexey A Shadrin, Olivia Skrobot, Susan Slifer, Gijsje J L Snijders, Hilkka Soininen, Vincenzo Solfrizzi, Alina Solomon, Yeunjoo Song, Sandro Sorbi, Oscar Sotolongo-Grau, Gianfranco Spalletta, Annika Spottke, Alessio Squassina, Eystein Stordal, Juan Pablo Tartan, Lluís Tárraga, Niccolo Tesí, Anbupalam Thalamuthu, Tegos Thomas, Giuseppe Tosto, Latchezar Traykov, Lucio Tremolizzo, Anne Tybjærg-Hansen, Andre Uitterlinden, Abbe Ullgren, Ingun Ulstein, Sergi Valero, Otto Valladares, Christine Van Broeckhoven, Jeffery Vance, Badri N Vardarajan, Aad Van Der Lugt, Jasper Van Dongen, Jeroen Van Rooij, John Van Swieten, Rik Vandenberghe, Frans Verhey, Jean-Sébastien Vidal, Jonathan Vogelgsang, Martin Vyhnalek, Michael Wagner, David Wallon, Li-San Wang, Ruiqi Wang, Leonie Weinhold, Jens Wiltfang, Gill Windle, Bob Woods, Mary Yannakoulia, Habil Zare, Yi Zhao, Xiaoling Zhang, Congcong Zhu, Miren Zulaica, Lindsay A Farrer, Bruce M Psaty, Mohsen Ghanbari, Towfique Raj, Perminder Sachdev, Karen Mather, Frank Jessen, M Arfan Ikram, Alexandre De Mendonça, Jakub Hort, Magda Tsolaki, Margaret A Pericak-Vance, Philippe Amouyel, Julie Williams, Ruth Frikke-Schmidt, Jordi Clarimon, Jean-François Deleuze, Giacomina Rossi, Sudha Seshadri, Ole A Andreassen, Martin Ingelsson, Mikko Hiltunen, Kristel Sleegers, Gerard D Schellenberg, Cornelia M Van Duijn, Rebecca Sims, Wiesje M Van Der Flier, Agustín Ruiz, Alfredo Ramirez, Jean-Charles Lambert

Journal Articles

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly …

A Genome-Wide Association Study Discovers 46 Loci Of The Human Metabolome In The Hispanic Community Health Study/Study Of Latinos, Elena V Feofanova, Han Chen, Yulin Dai, Peilin Jia, Megan L Grove, Alanna C Morrison, Qibin Qi, Martha Daviglus, Jianwen Cai, Kari E North, Cathy C Laurie, Robert C Kaplan, Eric Boerwinkle, Bing Yu

Journal Articles

Variation in levels of the human metabolome reflect changes in homeostasis, providing a window into health and disease. The genetic impact on circulating metabolites in Hispanics, a population with high cardiometabolic disease burden, is largely unknown. We conducted genome-wide association analyses on 640 circulating metabolites in 3,926 Hispanic Community Health Study/Study of Latinos participants. The estimated heritability for 640 metabolites ranged between 0%-54% with a median at 2.5%. We discovered 46 variant-metabolite pairs (p value < 1.2 × 10

Gwas Of Qrs Duration Identifies New Loci Specific To Hispanic/Latino Populations, Brenton R Swenson, Tin Louie, Henry J Lin, Raúl Méndez-Giráldez, Jennifer E Below, Cathy C Laurie, Kathleen F Kerr, Heather Highland, Timothy A Thornton, Kelli K Ryckman, Charles Kooperberg, Elsayed Z Soliman, Amanda A Seyerle, Xiuqing Guo, Kent D Taylor, Jie Yao, Susan R Heckbert, Dawood Darbar, Lauren E Petty, Barbara Mcknight, Susan Cheng, Natalie A Bello, Eric A Whitsel, Craig L Hanis, Mike A Nalls, Daniel S Evans, Jerome I Rotter, Tamar Sofer, Christy L Avery, Nona Sotoodehnia

Journal Articles

BACKGROUND: The electrocardiographically quantified QRS duration measures ventricular depolarization and conduction. QRS prolongation has been associated with poor heart failure prognosis and cardiovascular mortality, including sudden death. While previous genome-wide association studies (GWAS) have identified 32 QRS SNPs across 26 loci among European, African, and Asian-descent populations, the genetics of QRS among Hispanics/Latinos has not been previously explored.

METHODS: We performed a GWAS of QRS duration among Hispanic/Latino ancestry populations (n = 15,124) from four studies using 1000 Genomes imputed genotype data (adjusted for age, sex, global ancestry, clinical and study-specific covariates). Study-specific results were combined using fixed-effects, inverse variance-weighted …

Multiple Independent Genetic Factors At Nos1ap Modulate The Qt Interval In A Multi-Ethnic Population, Dan E. Arking, Amit Khera, Chao Xing, W H Linda Kao, Wendy Post, Eric Boerwinkle, Aravinda Chakravarti

Journal Articles

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples …