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1. Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI

Author

Yang, Yunju, Knol, Maria J, Wang, Ruiqi, Mishra, Aniket, Liu, Dan, Luciano, Michelle, Teumer, Alexander, Armstrong, Nicola, Bis, Joshua C, Jhun, Min A, Li, Shuo, Adams, Hieab HH, Aziz, Nasir Ahmad, Bastin, Mark E, Bourgey, Mathieu, Brody, Jennifer A, Frenzel, Stefan, Gottesman, Rebecca F, Hosten, Norbert, Hou, Lifang, Kardia, Sharon LR, Lohner, Valerie, Marquis, Pascale, Maniega, Susana Muñoz, Satizabal, Claudia L, Sorond, Farzaneh A, Valdés Hernández, Maria C, van Duijn, Cornelia M, Vernooij, Meike W, Wittfeld, Katharina, Yang, Qiong, Zhao, Wei, Boerwinkle, Eric, Levy, Daniel, Deary, Ian J, Jiang, Jiyang, Mather, Karen A, Mosley, Thomas H, Psaty, Bruce M, Sachdev, Perminder S, Smith, Jennifer A, Sotoodehnia, Nona, DeCarli, Charles S, Breteler, Monique MB, Ikram, M Arfan, Grabe, Hans J, Wardlaw, Joanna, Longstreth, WT, Launer, Lenore J, Seshadri, Sudha, Debette, Stephanie, and Fornage, Myriam

Subjects
Health Sciences, Genetics, Aging, Brain Disorders, Neurosciences, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Middle Aged, Humans, Aged, White Matter, Genome-Wide Association Study, Brain, DNA Methylation, Magnetic Resonance Imaging, Epigenesis, Genetic, Protein-Arginine N-Methyltransferases, Repressor Proteins, epigenome-wide association study, white matter hyperintensities, cerebral small vessel disease, integrative cross-omics analysis, blood-brain barrier dysfunction, blood–brain barrier dysfunction, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA methylation has received little attention. We investigated the association between white matter hyperintensity burden and DNA methylation in blood at ∼450 000 cytosine-phosphate-guanine (CpG) sites in 9732 middle-aged to older adults from 14 community-based studies. Single CpG and region-based association analyses were carried out. Functional annotation and integrative cross-omics analyses were performed to identify novel genes underlying the relationship between DNA methylation and white matter hyperintensities. We identified 12 single CpG and 46 region-based DNA methylation associations with white matter hyperintensity burden. Our top discovery single CpG, cg24202936 (P = 7.6 × 10-8), was associated with F2 expression in blood (P = 6.4 × 10-5) and co-localized with FOLH1 expression in brain (posterior probability = 0.75). Our top differentially methylated regions were in PRMT1 and in CCDC144NL-AS1, which were also represented in single CpG associations (cg17417856 and cg06809326, respectively). Through Mendelian randomization analyses cg06809326 was putatively associated with white matter hyperintensity burden (P = 0.03) and expression of CCDC144NL-AS1 possibly mediated this association. Differentially methylated region analysis, joint epigenetic association analysis and multi-omics co-localization analysis consistently identified a role of DNA methylation near SH3PXD2A, a locus previously identified in genome-wide association studies of white matter hyperintensities. Gene set enrichment analyses revealed functions of the identified DNA methylation loci in the blood-brain barrier and in the immune response. Integrative cross-omics analysis identified 19 key regulatory genes in two networks related to extracellular matrix organization, and lipid and lipoprotein metabolism. A drug-repositioning analysis indicated antihyperlipidaemic agents, more specifically peroxisome proliferator-activated receptor-alpha, as possible target drugs for white matter hyperintensities. Our epigenome-wide association study and integrative cross-omics analyses implicate novel genes influencing white matter hyperintensity burden, which converged on pathways related to the immune response and to a compromised blood-brain barrier possibly due to disrupted cell-cell and cell-extracellular matrix interactions. The results also suggest that antihyperlipidaemic therapy may contribute to lowering risk for white matter hyperintensities possibly through protection against blood-brain barrier disruption.

Published
2023

2. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Temprano‐Sagrera, Gerard, Sitlani, Colleen M, Bone, William P, Martin‐Bornez, Miguel, Voight, Benjamin F, Morrison, Alanna C, Damrauer, Scott M, de Vries, Paul S, Smith, Nicholas L, Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank WG, Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek PM, Pankratz, Nathan, Peyser, Patricia A, Elliot, Paul, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, and Braekkan, Sigrid K

Subjects
Genetics, Biotechnology, Human Genome, Atherosclerosis, Prevention, Cardiovascular, Hematology, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular Diseases, Factor XI, Genetic Predisposition to Disease, Genome-Wide Association Study, Hemostasis, Hemostatics, Humans, Phenotype, Polymorphism, Single Nucleotide, Tissue Plasminogen Activator, blood coagulation, cardiovascular diseases, genetic pleiotropy, genome-wide association study, hemostasis, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract

BackgroundMulti-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes.ObjectivesTo discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events.MethodsSummary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10-9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27).ResultsAcross the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes.ConclusionsThe discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.

Published
2022

3. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

Author

Dehghan, Abbas, Heath, Adam S., Morrison, Alanna C., Reiner, Alex P., Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M., Hayward, Caroline, Ward-Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P., Tregouet, David A., Mook-Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W., Leebeek, Frank W.G., Rosendaal, Frits R., Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A., Bressler, Jan, Huffman, Jennifer E., Rotter, Jerome I., Yao, Jie, Wilson, James F., Bis, Joshua C., Hahn, Julie M., Desch, Karl C., Wiggins, Kerri L., Díez-Ahijado, Laia, Raffield, Laura M., Bielak, Lawrence F., Yanek, Lisa R., Kleber, Marcus E., Sabater-Lleal, Maria, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Conomos, Matthew P., Liu, Melissa, Brown, Michael R., Jhun, Min-A, Chen, Ming-Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L., Peyser, Patricia A., Elliot, Paul, de Vries, Paul S., Wei, Peng, Wild, Philipp S., Morange, Pierre E., van der Harst, Pim, Yang, Qiong, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M., Cox, Simon R., Trompet, Stella, Felix, Stephan B., Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Gallego-Fabrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullell, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martin-Campos, Jesús M., Sobrino, Tomás, Castillo, José, Millán, Mònica, Muñoz-Narbona, Lucía, López-Cancio, Elena, Ribó, Marc, Alvarez-Sabin, Jose, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan F., Segura, Tomas, Serrano-Heras, Gemma, Marti-Fabregas, Joan, Freijo-Guerrero, Marimar, Moniche, Francisco, Castellanos, Maria del Mar, and Fernández-Cadenas, Israel

Published
2024
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4. An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

Author

Liu, Jun, Carnero-Montoro, Elena, van Dongen, Jenny, Lent, Samantha, Nedeljkovic, Ivana, Ligthart, Symen, Tsai, Pei-Chien, Martin, Tiphaine C, Mandaviya, Pooja R, Jansen, Rick, Peters, Marjolein J, Duijts, Liesbeth, Jaddoe, Vincent WV, Tiemeier, Henning, Felix, Janine F, Willemsen, Gonneke, de Geus, Eco JC, Chu, Audrey Y, Levy, Daniel, Hwang, Shih-Jen, Bressler, Jan, Gondalia, Rahul, Salfati, Elias L, Herder, Christian, Hidalgo, Bertha A, Tanaka, Toshiko, Moore, Ann Zenobia, Lemaitre, Rozenn N, Jhun, Min A, Smith, Jennifer A, Sotoodehnia, Nona, Bandinelli, Stefania, Ferrucci, Luigi, Arnett, Donna K, Grallert, Harald, Assimes, Themistocles L, Hou, Lifang, Baccarelli, Andrea, Whitsel, Eric A, van Dijk, Ko Willems, Amin, Najaf, Uitterlinden, André G, Sijbrands, Eric JG, Franco, Oscar H, Dehghan, Abbas, Spector, Tim D, Dupuis, Josée, Hivert, Marie-France, Rotter, Jerome I, Meigs, James B, Pankow, James S, van Meurs, Joyce BJ, Isaacs, Aaron, Boomsma, Dorret I, Bell, Jordana T, Demirkan, Ayşe, and van Duijn, Cornelia M

Subjects
Biological Sciences, Genetics, Nutrition, Diabetes, Human Genome, Obesity, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Aged, Aged, 80 and over, Computer Simulation, CpG Islands, DNA Methylation, Diabetes Mellitus, Type 2, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Profiling, Gene Expression Regulation, Genome-Wide Association Study, Glucose, Homeostasis, Humans, Insulin, Male, Metabolic Networks and Pathways, Middle Aged, Polymorphism, Single Nucleotide, Young Adult
Abstract

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.

Published
2019

5. DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation

Author

Richard, Melissa A, Huan, Tianxiao, Ligthart, Symen, Gondalia, Rahul, Jhun, Min A, Brody, Jennifer A, Irvin, Marguerite R, Marioni, Riccardo, Shen, Jincheng, Tsai, Pei-Chien, Montasser, May E, Jia, Yucheng, Syme, Catriona, Salfati, Elias L, Boerwinkle, Eric, Guan, Weihua, Mosley, Thomas H, Bressler, Jan, Morrison, Alanna C, Liu, Chunyu, Mendelson, Michael M, Uitterlinden, André G, van Meurs, Joyce B, Consortium, BIOS, Heijmans, Bastiaan T, Hoen, Peter AC ’t, van Meurs, Joyce, Isaacs, Aaron, Jansen, Rick, Franke, Lude, Boomsma, Dorret I, Pool, René, van Dongen, Jenny, Hottenga, Jouke J, van Greevenbroek, Marleen MJ, Stehouwer, Coen DA, van der Kallen, Carla JH, Schalkwijk, Casper G, Wijmenga, Cisca, Zhernakova, Alexandra, Tigchelaar, Ettje F, Slagboom, P Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H, van den Berg, Leonard H, van Duijn, Cornelia M, Hofman, Albert, Jhamai, P Mila, Verbiest, Michael, Suchiman, H Eka D, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, van ’t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Zhernakova, Dasha V, Luijk, René, Bonder, Marc Jan, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M, Swertz, Morris A, van Zwet, Erik W, Franco, Oscar H, Zhang, Guosheng, Li, Yun, Stewart, James D, Bis, Joshua C, Psaty, Bruce M, Chen, Yii-Der Ida, Kardia, Sharon LR, Zhao, Wei, Turner, Stephen T, Absher, Devin, Aslibekyan, Stella, Starr, John M, McRae, Allan F, Hou, Lifang, Just, Allan C, Schwartz, Joel D, Vokonas, Pantel S, Menni, Cristina, Spector, Tim D, Shuldiner, Alan, Damcott, Coleen M, Rotter, Jerome I, Palmas, Walter, Liu, Yongmei, and Paus, Tomáš

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Aged, Blood Pressure, CpG Islands, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Genetic Variation, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Middle Aged, Nerve Tissue Proteins, Quantitative Trait Loci, Tetraspanins, BIOS Consortium, DNA methylation, Mendelian randomization, blood pressure, epigenome-wide association study, gene expression, sequence variation, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10-7; replication: N = 7,182, p  30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.

Published
2017

6. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

Author

Natarajan, Pradeep, Bis, Joshua C, Bielak, Lawrence F, Cox, Amanda J, Dörr, Marcus, Feitosa, Mary F, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, Isaacs, Aaron, Jhun, Min A, Kavousi, Maryam, Li-Gao, Ruifang, Lyytikäinen, Leo-Pekka, Marioni, Riccardo E, Schminke, Ulf, Stitziel, Nathan O, Tada, Hayato, van Setten, Jessica, Smith, Albert V, Vojinovic, Dina, Yanek, Lisa R, Yao, Jie, Yerges-Armstrong, Laura M, Amin, Najaf, Baber, Usman, Borecki, Ingrid B, Carr, J Jeffrey, Chen, Yii-Der Ida, Cupples, L Adrienne, de Jong, Pim A, de Koning, Harry, de Vos, Bob D, Demirkan, Ayse, Fuster, Valentin, Franco, Oscar H, Goodarzi, Mark O, Harris, Tamara B, Heckbert, Susan R, Heiss, Gerardo, Hoffmann, Udo, Hofman, Albert, Išgum, Ivana, Jukema, J Wouter, Kähönen, Mika, Kardia, Sharon LR, Kral, Brian G, Launer, Lenore J, Massaro, Joe, Mehran, Roxana, Mitchell, Braxton D, Mosley, Thomas H, de Mutsert, Renée, Newman, Anne B, Nguyen, Khanh-Dung, North, Kari E, O'Connell, Jeffrey R, Oudkerk, Matthijs, Pankow, James S, Peloso, Gina M, Post, Wendy, Province, Michael A, Raffield, Laura M, Raitakari, Olli T, Reilly, Dermot F, Rivadeneira, Fernando, Rosendaal, Frits, Sartori, Samantha, Taylor, Kent D, Teumer, Alexander, Trompet, Stella, Turner, Stephen T, Uitterlinden, Andre G, Vaidya, Dhananjay, van der Lugt, Aad, Völker, Uwe, Wardlaw, Joanna M, Wassel, Christina L, Weiss, Stefan, Wojczynski, Mary K, Becker, Diane M, Becker, Lewis C, Boerwinkle, Eric, Bowden, Donald W, Deary, Ian J, Dehghan, Abbas, Felix, Stephan B, Gudnason, Vilmundur, Lehtimäki, Terho, Mathias, Rasika, Mook-Kanamori, Dennis O, Psaty, Bruce M, Rader, Daniel J, Rotter, Jerome I, Wilson, James G, van Duijn, Cornelia M, Völzke, Henry, Kathiresan, Sekar, Peyser, Patricia A, and O'Donnell, Christopher J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease - Coronary Heart Disease, Aging, Human Genome, Atherosclerosis, Cardiovascular, Heart Disease, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Apolipoprotein B-100, Apolipoprotein E2, Asymptomatic Diseases, Black People, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cholesterol, LDL, Computed Tomography Angiography, Coronary Angiography, Coronary Artery Disease, Exome, Gene Frequency, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Odds Ratio, Oligonucleotide Array Sequence Analysis, Phenotype, Prognosis, Risk Assessment, Risk Factors, Vascular Calcification, White People, carotid intima-media thickness, coronary artery calcification, exome, genome-wide association study, genomics, CHARGE Consortium, carotid intima–media thickness, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundThe burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease.Methods and resultsWe studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima-media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology). Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and carotid intima-media thickness. APOB p.Arg3527Gln was associated with 4-fold excess CAC (P=3×10-10). The APOE ε2 allele (p.Arg176Cys) was associated with both 22.3% reduced CAC (P=1×10-12) and 1.4% reduced carotid intima-media thickness (P=4×10-14) in carriers compared with noncarriers. In secondary analyses conditioning on low-density lipoprotein cholesterol concentration, the ε2 protective association with CAC, although attenuated, remained strongly significant. Additionally, the presence of ε2 was associated with reduced risk for coronary heart disease (odds ratio 0.77; P=1×10-11).ConclusionsExome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE ε2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease.

Published
2016

7. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Author

Liu, Ching-Ti, Raghavan, Sridharan, Maruthur, Nisa, Kabagambe, Edmond Kato, Hong, Jaeyoung, Ng, Maggie CY, Hivert, Marie-France, Lu, Yingchang, An, Ping, Bentley, Amy R, Drolet, Anne M, Gaulton, Kyle J, Guo, Xiuqing, Armstrong, Loren L, Irvin, Marguerite R, Li, Man, Lipovich, Leonard, Rybin, Denis V, Taylor, Kent D, Agyemang, Charles, Palmer, Nicholette D, Cade, Brian E, Chen, Wei-Min, Dauriz, Marco, Delaney, Joseph AC, Edwards, Todd L, Evans, Daniel S, Evans, Michele K, Lange, Leslie A, Leong, Aaron, Liu, Jingmin, Liu, Yongmei, Nayak, Uma, Patel, Sanjay R, Porneala, Bianca C, Rasmussen-Torvik, Laura J, Snijder, Marieke B, Stallings, Sarah C, Tanaka, Toshiko, Yanek, Lisa R, Zhao, Wei, Becker, Diane M, Bielak, Lawrence F, Biggs, Mary L, Bottinger, Erwin P, Bowden, Donald W, Chen, Guanjie, Correa, Adolfo, Couper, David J, Crawford, Dana C, Cushman, Mary, Eicher, John D, Fornage, Myriam, Franceschini, Nora, Fu, Yi-Ping, Goodarzi, Mark O, Gottesman, Omri, Hara, Kazuo, Harris, Tamara B, Jensen, Richard A, Johnson, Andrew D, Jhun, Min A, Karter, Andrew J, Keller, Margaux F, Kho, Abel N, Kizer, Jorge R, Krauss, Ronald M, Langefeld, Carl D, Li, Xiaohui, Liang, Jingling, Liu, Simin, Lowe, William L, Mosley, Thomas H, North, Kari E, Pacheco, Jennifer A, Peyser, Patricia A, Patrick, Alan L, Rice, Kenneth M, Selvin, Elizabeth, Sims, Mario, Smith, Jennifer A, Tajuddin, Salman M, Vaidya, Dhananjay, Wren, Mary P, Yao, Jie, Zhu, Xiaofeng, Ziegler, Julie T, Zmuda, Joseph M, Zonderman, Alan B, Zwinderman, Aeilko H, Consortium, AAAG, Consortium, CARe, Consortium, COGENT-BP, Consortium, eMERGE, Consortium, MEDIA, Adeyemo, Adebowale, Boerwinkle, Eric, Ferrucci, Luigi, Hayes, M Geoffrey, and Kardia, Sharon LR

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Health Disparities, Human Genome, Diabetes, Minority Health, Metabolic and endocrine, Asian People, Black People, Blood Glucose, Diabetes Mellitus, Type 2, Enhancer Elements, Genetic, Ethnicity, Fasting, Female, Gene Frequency, Genome-Wide Association Study, Humans, Insulin, Insulin Resistance, Introns, Islets of Langerhans, Male, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Racial Groups, Transcription Factors, White People, AAAG Consortium, CARe Consortium, COGENT-BP Consortium, eMERGE Consortium, MEDIA Consortium, MAGIC Consortium, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

Published
2016

8. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

Author

de Vries, Paul S, Chasman, Daniel I, Sabater-Lleal, Maria, Chen, Ming-Huei, Huffman, Jennifer E, Steri, Maristella, Tang, Weihong, Teumer, Alexander, Marioni, Riccardo E, Grossmann, Vera, Hottenga, Jouke J, Trompet, Stella, Müller-Nurasyid, Martina, Zhao, Jing Hua, Brody, Jennifer A, Kleber, Marcus E, Guo, Xiuqing, Wang, Jie Jin, Auer, Paul L, Attia, John R, Yanek, Lisa R, Ahluwalia, Tarunveer S, Lahti, Jari, Venturini, Cristina, Tanaka, Toshiko, Bielak, Lawrence F, Joshi, Peter K, Rocanin-Arjo, Ares, Kolcic, Ivana, Navarro, Pau, Rose, Lynda M, Oldmeadow, Christopher, Riess, Helene, Mazur, Johanna, Basu, Saonli, Goel, Anuj, Yang, Qiong, Ghanbari, Mohsen, Willemsen, Gonneke, Rumley, Ann, Fiorillo, Edoardo, de Craen, Anton JM, Grotevendt, Anne, Scott, Robert, Taylor, Kent D, Delgado, Graciela E, Yao, Jie, Kifley, Annette, Kooperberg, Charles, Qayyum, Rehan, Lopez, Lorna M, Berentzen, Tina L, Räikkönen, Katri, Mangino, Massimo, Bandinelli, Stefania, Peyser, Patricia A, Wild, Sarah, Trégouët, David-Alexandre, Wright, Alan F, Marten, Jonathan, Zemunik, Tatijana, Morrison, Alanna C, Sennblad, Bengt, Tofler, Geoffrey, de Maat, Moniek PM, de Geus, Eco JC, Lowe, Gordon D, Zoledziewska, Magdalena, Sattar, Naveed, Binder, Harald, Völker, Uwe, Waldenberger, Melanie, Khaw, Kay-Tee, Mcknight, Barbara, Huang, Jie, Jenny, Nancy S, Holliday, Elizabeth G, Qi, Lihong, Mcevoy, Mark G, Becker, Diane M, Starr, John M, Sarin, Antti-Pekka, Hysi, Pirro G, Hernandez, Dena G, Jhun, Min A, Campbell, Harry, Hamsten, Anders, Rivadeneira, Fernando, Mcardle, Wendy L, Slagboom, P Eline, Zeller, Tanja, Koenig, Wolfgang, Psaty, Bruce M, Haritunians, Talin, Liu, Jingmin, Palotie, Aarno, Uitterlinden, André G, Stott, David J, Hofman, Albert, and Franco, Oscar H

Subjects
Biological Sciences, Genetics, Human Genome, Adult, Aged, Aged, 80 and over, Female, Fibrinogen, Genetic Loci, Genome-Wide Association Study, Humans, INDEL Mutation, Male, Middle Aged, Polymorphism, Single Nucleotide, White People, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

Published
2016

9. A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

Author

Jhun, Min-A, Mendelson, Michael, Wilson, Rory, Gondalia, Rahul, Joehanes, Roby, Salfati, Elias, Zhao, Xiaoping, Braun, Kim Valeska Emilie, Do, Anh Nguyet, Hedman, Åsa K., Zhang, Tao, Carnero-Montoro, Elena, Shen, Jincheng, Bartz, Traci M., Brody, Jennifer A., Montasser, May E., O’Connell, Jeff R., Yao, Chen, Xia, Rui, Boerwinkle, Eric, Grove, Megan, Guan, Weihua, Liliane, Pfeiffer, Singmann, Paula, Müller-Nurasyid, Martina, Meitinger, Thomas, Gieger, Christian, Peters, Annette, Zhao, Wei, Ware, Erin B., Smith, Jennifer A., Dhana, Klodian, van Meurs, Joyce, Uitterlinden, Andre, Ikram, Mohammad Arfan, Ghanbari, Mohsen, Zhi, Deugi, Gustafsson, Stefan, Lind, Lars, Li, Shengxu, Sun, Dianjianyi, Spector, Tim D., Chen, Yii-der Ida, Damcott, Coleen, Shuldiner, Alan R., Absher, Devin M., Horvath, Steve, Tsao, Philip S., Kardia, Sharon, Psaty, Bruce M., Sotoodehnia, Nona, Bell, Jordana T., Ingelsson, Erik, Chen, Wei, Dehghan, Abbas, Arnett, Donna K., Waldenberger, Melanie, Hou, Lifang, Whitsel, Eric A., Baccarelli, Andrea, Levy, Daniel, Fornage, Myriam, Irvin, Marguerite R., and Assimes, Themistocles L.

Published
2021
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10. Publisher Correction: A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

Author

Jhun, Min-A, Mendelson, Michael, Wilson, Rory, Gondalia, Rahul, Joehanes, Roby, Salfati, Elias, Zhao, Xiaoping, Braun, Kim Valeska Emilie, Do, Anh Nguyet, Hedman, Åsa K., Zhang, Tao, Carnero-Montoro, Elena, Shen, Jincheng, Bartz, Traci M., Brody, Jennifer A., Montasser, May E., O’Connell, Jeff R., Yao, Chen, Xia, Rui, Boerwinkle, Eric, Grove, Megan, Guan, Weihua, Liliane, Pfeiffer, Singmann, Paula, Müller-Nurasyid, Martina, Meitinger, Thomas, Gieger, Christian, Peters, Annette, Zhao, Wei, Ware, Erin B., Smith, Jennifer A., Dhana, Klodian, van Meurs, Joyce, Uitterlinden, Andre, Ikram, Mohammad Arfan, Ghanbari, Mohsen, Zhi, Deugi, Gustafsson, Stefan, Lind, Lars, Li, Shengxu, Sun, Dianjianyi, Spector, Tim D., Chen, Yii-der Ida, Damcott, Coleen, Shuldiner, Alan R., Absher, Devin M., Horvath, Steve, Tsao, Philip S., Kardia, Sharon, Psaty, Bruce M., Sotoodehnia, Nona, Bell, Jordana T., Ingelsson, Erik, Chen, Wei, Dehghan, Abbas, Arnett, Donna K., Waldenberger, Melanie, Hou, Lifang, Whitsel, Eric A., Baccarelli, Andrea, Levy, Daniel, Fornage, Myriam, Irvin, Marguerite R., and Assimes, Themistocles L.

Published
2021
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11. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Palmer Allred, Nicholette (Nichole), Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Cho, Michael H., Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Holly, Kramer, Hong, Elliott, Hoth, Karin, (Agnes) Hsiung, Chao, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A., Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kachroo, Priyadarshini, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun Shawn, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lubitz, Steven, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah A., Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton, Montasser, May E., Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Su-Lasky, Jessica, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Wang, Fei Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zekavat, Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, Zoellner, Sebastian, Hecker, Julian, Chawes, Bo L., Ahluwalia, Tarunveer S., Kelly, Rachel S., Chu, Su H., Virkud, Yamini V., Huang, Mengna, Barnes, Kathleen C., Burchard, Esteban G., Eng, Celeste, Hu, Donglei, Celedón, Juan C., Levin, Albert M., Gui, Hongsheng, Forno, Erick, Mak, Angel C.Y., Avila, Lydiana, Soto-Quiros, Manuel E., Cloutier, Michelle M., Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A., Weiss, Scott T., and Lasky-Su, Jessica A.

Published
2019
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12. DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis

Author

Ward-Caviness, Cavin K., Huffman, Jennifer E., Everett, Karl, Germain, Marine, van Dongen, Jenny, Hill, W. David, Jhun, Min A., Brody, Jennifer A., Ghanbari, Mohsen, Du, Lei, Roetker, Nicholas S., de Vries, Paul S., Waldenberger, Melanie, Gieger, Christian, Wolf, Petra, Prokisch, Holger, Koenig, Wolfgang, O'Donnell, Christopher J., Levy, Daniel, Liu, Chunyu, Truong, Vinh, Wells, Philip S., Trégouët, David-Alexandre, Tang, Weihong, Morrison, Alanna C., Boerwinkle, Eric, Wiggins, Kerri L., McKnight, Barbara, Guo, Xiuqing, Psaty, Bruce M., Sotoodenia, Nona, Boomsma, Dorret I., Willemsen, Gonneke, Ligthart, Lannie, Deary, Ian J., Zhao, Wei, Ware, Erin B., Kardia, Sharon L.R., Van Meurs, Joyce B.J., Uitterlinden, Andre G., Franco, Oscar H., Eriksson, Per, Franco-Cereceda, Anders, Pankow, James S., Johnson, Andrew D., Gagnon, France, Morange, Pierre-Emmanuel, de Geus, Eco J.C., Starr, John M., Smith, Jennifer A., Dehghan, Abbas, Björck, Hanna M., Smith, Nicholas L., and Peters, Annette

Published
2018
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13. Meta-analysis of epigenome-wide association studies of cognitive abilities

Author

Marioni, Riccardo E., McRae, Allan F., Bressler, Jan, Colicino, Elena, Hannon, Eilis, Li, Shuo, Prada, Diddier, Smith, Jennifer A, Trevisi, Letizia, Tsai, Pei-Chien, Vojinovic, Dina, Simino, Jeannette, Levy, Daniel, Liu, Chunyu, Mendelson, Michael, Satizabal, Claudia L., Yang, Qiong, Jhun, Min A., Kardia, Sharon L. R., Zhao, Wei, Bandinelli, Stefania, Ferrucci, Luigi, Hernandez, Dena G., Singleton, Andrew B., Harris, Sarah E., Starr, John M., Kiel, Douglas P., McLean, Robert R., Just, Allan C., Schwartz, Joel, Spiro, III, Avron, Vokonas, Pantel, Amin, Najaf, Ikram, M. Arfan, Uitterlinden, Andre G., van Meurs, Joyce B. J., Spector, Tim D., Steves, Claire, Baccarelli, Andrea A., Bell, Jordana T., van Duijn, Cornelia M., Fornage, Myriam, Hsu, Yi-Hsiang, Mill, Jonathan, Mosley, Thomas H., Seshadri, Sudha, and Deary, Ian J.

Published
2018
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14. Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus

Author

Stacey, David, Chen, Lingyan, Stanczyk, Paulina J, Howson, Joanna MM, Mason, Amy M, Burgess, Stephen, MacDonald, Stephen, Langdown, Jonathan, McKinney, Harriett, Downes, Kate, Farahi, Neda, Peters, James E, Basu, Saonli, Pankow, James S, Tang, Weihong, Pankratz, Nathan, Sabater-Lleal, Maria, De Vries, Paul S, Smith, Nicholas L, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, Van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward-Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook-Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank WG, Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Conomos, Matthew P, Liu, Melissa, Brown, Michael R, Jhun, Min-A, Chen, Ming-Huei, De Maat, Moniek PM, Peyser, Patricia A, Elliot, Paul, Wei, Peng, Wild, Philipp S, Morange, Pierre E, Van Der Harst, Pim, Yang, Qiong, Le, Ngoc-Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Koenig, Wolfgang, Jukema, J Wouter, Guo, Xiuqing, Gelinas, Amy D, Schneider, Daniel J, Janjic, Nebojsa, Samani, Nilesh J, Ye, Shu, Summers, Charlotte, Chilvers, Edwin R, Danesh, John, Paul, Dirk S, Chen, Lingyan [0000-0003-3750-6761], Howson, Joanna MM [0000-0001-7618-0050], Mason, Amy M [0000-0002-8019-0777], Burgess, Stephen [0000-0001-5365-8760], Peters, James E [0000-0002-9415-3440], Pankow, James S [0000-0001-7076-483X], Pankratz, Nathan [0000-0001-5958-693X], Sabater-Lleal, Maria [0000-0002-0128-379X], Schneider, Daniel J [0000-0001-6830-0905], Samani, Nilesh J [0000-0002-3286-8133], Ye, Shu [0000-0002-4126-4278], Summers, Charlotte [0000-0002-7269-2873], Chilvers, Edwin R [0000-0002-4230-9677], Paul, Dirk S [0000-0002-8230-0116], and Apollo - University of Cambridge Repository

Subjects
13/31, 13/1, 692/4019/592/2727, 45/43, article, 631/208/212/2301, 45/88, 13/106
Abstract

Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, attenuating leukocyte–endothelial cell adhesion and vascular inflammation. We also associate PROCR-219Gly with an increased pro-thrombotic state via coagulation factor VII, a ligand of EPCR. Our study, which links PROCR-219Gly to CAD through anti-inflammatory mechanisms and to VTE through pro-thrombotic mechanisms, provides a framework to reveal the mechanisms underlying similar cross-phenotype associations.

Published
2022

15. Clustering Method to Identify Gene Sets with Similar Expression Profiles in Adjacent Chromosomal Regions

Author

Jhun, Min A., Park, Taesung, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Cabestany, Joan, editor, Sandoval, Francisco, editor, Prieto, Alberto, editor, and Corchado, Juan M., editor

Published
2009
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16. An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels

Author

Montasser, May E., O’Hare, Elizabeth A., Wang, Xiaochun, Howard, Alicia D., McFarland, Rebecca, Perry, James A., Ryan, Kathleen A., Rice, Kenneth, Jaquish, Cashell E., Shuldiner, Alan R., Miller, Michael, Mitchell, Braxton D., Zaghloul, Norann A., Chang, Yen-Pei C., Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette P., Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Debora, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Graham Barr, R., Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russel, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carlson, Sara, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Malia, Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Charles Gu, C., Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Huston, Haley, Hwu, Chii Min, Irvin, Marguerite, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton, Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi Johns, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O’Connell, Jeff, O’Connor, Tim, Heather, Ochs-Balcom, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Pattison, Jessica Tangarone, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Larry, Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Benjamin Shoemaker, M., Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Fei Wang, Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Keoki Williams, L., Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, and Zoellner, Sebastian

Published
2018
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17. Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI

Author

Yang, Yunju, primary, Knol, Maria J, additional, Wang, Ruiqi, additional, Mishra, Aniket, additional, Liu, Dan, additional, Luciano, Michelle, additional, Teumer, Alexander, additional, Armstrong, Nicola, additional, Bis, Joshua C, additional, Jhun, Min A, additional, Li, Shuo, additional, Adams, Hieab H H, additional, Aziz, Nasir Ahmad, additional, Bastin, Mark E, additional, Bourgey, Mathieu, additional, Brody, Jennifer A, additional, Frenzel, Stefan, additional, Gottesman, Rebecca F, additional, Hosten, Norbert, additional, Hou, Lifang, additional, Kardia, Sharon L R, additional, Lohner, Valerie, additional, Marquis, Pascale, additional, Maniega, Susana Muñoz, additional, Satizabal, Claudia L, additional, Sorond, Farzaneh A, additional, Valdés Hernández, Maria C, additional, van Duijn, Cornelia M, additional, Vernooij, Meike W, additional, Wittfeld, Katharina, additional, Yang, Qiong, additional, Zhao, Wei, additional, Boerwinkle, Eric, additional, Levy, Daniel, additional, Deary, Ian J, additional, Jiang, Jiyang, additional, Mather, Karen A, additional, Mosley, Thomas H, additional, Psaty, Bruce M, additional, Sachdev, Perminder S, additional, Smith, Jennifer A, additional, Sotoodehnia, Nona, additional, DeCarli, Charles S, additional, Breteler, Monique M B, additional, Ikram, M Arfan, additional, Grabe, Hans J, additional, Wardlaw, Joanna, additional, Longstreth, W T, additional, Launer, Lenore J, additional, Seshadri, Sudha, additional, Debette, Stephanie, additional, and Fornage, Myriam, additional

Published
2022
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19. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R., Kjaer, Troels R., Fine, Rebecca S., Lu, Yingchang, Schurmann, Claudia, Highland, Heather M., Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E., Lamparter, David, Stirrups, Kathleen E., Turcot, Valérie, Young, Kristin L., Winkler, Thomas W., Esko, Tõnu, Karaderi, Tugce, Locke, Adam E., Masca, Nicholas G. D., Ng, Maggie C. Y., Mudgal, Poorva, Rivas, Manuel A., Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K., Adair, Linda S., Alam, Dewan S., Albrecht, Eva, Allin, Kristine H., Allison, Matthew, Amouyel, Philippe, Appel, Emil V., Arveiler, Dominique, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Banas, Bernhard, Bang, Lia E., Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bonnycastle, Lori L., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Burt, Amber A., Butterworth, Adam S., Carey, David J., Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul I. W., de Borst, Gert J., de Denus, Simon, de Groot, Mark C. H., de Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., den Hollander, Anneke I., Dennis, Joe G., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M., Easton, Douglas F., Ebeling, Tapani, Edwards, Todd L., Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D., Feitosa, Mary F., Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M., Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franks, Paul W., Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D., Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Hayward, Caroline, He, Liang, Heid, Iris M., Heikkilä, Kauko, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L., Hovingh, Kees G., Howson, Joanna M. M., Hoyng, Carel B., Huang, Paul L., Hveem, Kristian, Ikram, Arfan M., Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jhun, Min A., Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jousilahti, Pekka, Jukema, Wouter J., Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A., Kitajima, Hidetoshi, Kluivers, Kirsten B., Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Küry, Sébastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A., Lange, Ethan M., Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Larson, Eric B., Lee, I-Te, Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jianʼan, Lubitz, Steven A., Lyytikäinen, Leo-Pekka, Mackey, David A., Madden, Pamela A. F., Manning, Alisa K., Männistö, Satu, Marenne, Gaëlle, Marten, Jonathan, Martin, Nicholas G., Mazul, Angela L., Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L., Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Ntalla, Ioanna, OʼConnel, Jeffrey R., Oksa, Heikki, Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Person, Thomas N., Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renström, Frida, Ridker, Paul M., Rioux, John D., Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert Vernon, Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Stumvoll, Michael, Surendran, Praveen, Hart, Leen M.ʼt, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Ulivi, Sheila, van der Laan, Sander W., Van Der Leij, Andries R., van Duijn, Cornelia M., van Schoor, Natasja M., van Setten, Jessica, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J., Warren, Helen R., Wessel, Jennifer, Willems, Sara M., Wilson, James G., Witte, Daniel R., Woods, Michael O., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I, Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I., Willer, Cristen J., Stefansson, Kari, Borecki, Ingrid B., Liu, Dajiang J., North, Kari E., Heard-Costa, Nancy L., Pers, Tune H., Lindgren, Cecilia M., Oxvig, Claus, Kutalik, Zoltán, Rivadeneira, Fernando, Loos, Ruth J. F., Frayling, Timothy M., Hirschhorn, Joel N., Deloukas, Panos, and Lettre, Guillaume

Published
2017
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21. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Author

Manning, Alisa K, Hivert, Marie-France, Scott, Robert A, Grimsby, Jonna L, Bouatia-Naji, Nabila, Chen, Han, Rybin, Denis, Liu, Ching-Ti, Bielak, Lawrence F, Prokopenko, Inga, Amin, Najaf, Barnes, Daniel, Cadby, Gemma, Hottenga, Jouke-Jan, Ingelsson, Erik, Jackson, Anne U, Johnson, Toby, Kanoni, Stavroula, Ladenvall, Claes, Lagou, Vasiliki, Lahti, Jari, Lecoeur, Cecile, Liu, Yongmei, Martinez-Larrad, Maria Teresa, Montasser, May E, Navarro, Pau, Perry, John R B, Rasmussen-Torvik, Laura J, Salo, Perttu, Sattar, Naveed, Shungin, Dmitry, Strawbridge, Rona J, Tanaka, Toshiko, van Duijn, Cornelia M, An, Ping, de Andrade, Mariza, Andrews, Jeanette S, Aspelund, Thor, Atalay, Mustafa, Aulchenko, Yurii, Balkau, Beverley, Bandinelli, Stefania, Beckmann, Jacques S, Beilby, John P, Bellis, Claire, Bergman, Richard N, Blangero, John, Boban, Mladen, Boehnke, Michael, Boerwinkle, Eric, Bonnycastle, Lori L, Boomsma, Dorret I, Borecki, Ingrid B, Böttcher, Yvonne, Bouchard, Claude, Brunner, Eric, Budimir, Danijela, Campbell, Harry, Carlson, Olga, Chines, Peter S, Clarke, Robert, Collins, Francis S, Corbatón-Anchuelo, Arturo, Couper, David, de Faire, Ulf, Dedoussis, George V, Deloukas, Panos, Dimitriou, Maria, Egan, Josephine M, Eiriksdottir, Gudny, Erdos, Michael R, Eriksson, Johan G, Eury, Elodie, Ferrucci, Luigi, Ford, Ian, Forouhi, Nita G, Fox, Caroline S, Franzosi, Maria Grazia, Franks, Paul W, Frayling, Timothy M, Froguel, Philippe, Galan, Pilar, de Geus, Eco, Gigante, Bruna, Glazer, Nicole L, Goel, Anuj, Groop, Leif, Gudnason, Vilmundur, Hallmans, Göran, Hamsten, Anders, Hansson, Ola, Harris, Tamara B, Hayward, Caroline, Heath, Simon, Hercberg, Serge, Hicks, Andrew A, Hingorani, Aroon, Hofman, Albert, Hui, Jennie, Hung, Joseph, Jarvelin, Marjo-Riitta, Jhun, Min A, Johnson, Paul C D, Jukema, J Wouter, Jula, Antti, Kao, W H, Kaprio, Jaakko, Kardia, Sharon L R, Keinanen-Kiukaanniemi, Sirkka, Kivimaki, Mika, Kolcic, Ivana, Kovacs, Peter, Kumari, Meena, Kuusisto, Johanna, Kyvik, Kirsten Ohm, Laakso, Markku, Lakka, Timo, Lannfelt, Lars, Lathrop, G Mark, Launer, Lenore J, Leander, Karin, Li, Guo, Lind, Lars, Lindstrom, Jaana, Lobbens, Stéphane, Loos, Ruth J F, Luan, Jian'an, Lyssenko, Valeriya, Mägi, Reedik, Magnusson, Patrik K E, Marmot, Michael, Meneton, Pierre, Mohlke, Karen L, Mooser, Vincent, Morken, Mario A, Miljkovic, Iva, Narisu, Narisu, O'Connell, Jeff, Ong, Ken K, Oostra, Ben A, Palmer, Lyle J, Palotie, Aarno, Pankow, James S, Peden, John F, Pedersen, Nancy L, Pehlic, Marina, Peltonen, Leena, Penninx, Brenda, Pericic, Marijana, Perola, Markus, Perusse, Louis, Peyser, Patricia A, Polasek, Ozren, Pramstaller, Peter P, Province, Michael A, Räikkönen, Katri, Rauramaa, Rainer, Rehnberg, Emil, Rice, Ken, Rotter, Jerome I, Rudan, Igor, Ruokonen, Aimo, Saaristo, Timo, Sabater-Lleal, Maria, Salomaa, Veikko, Savage, David B, Saxena, Richa, Schwarz, Peter, Seedorf, Udo, Sennblad, Bengt, Serrano-Rios, Manuel, Shuldiner, Alan R, Sijbrands, Eric J G, Siscovick, David S, Smit, Johannes H, Small, Kerrin S, Smith, Nicholas L, Smith, Albert Vernon, Stančáková, Alena, Stirrups, Kathleen, Stumvoll, Michael, Sun, Yan V, Swift, Amy J, Tönjes, Anke, Tuomilehto, Jaakko, Trompet, Stella, Uitterlinden, Andre G, Uusitupa, Matti, Vikström, Max, Vitart, Veronique, Vohl, Marie-Claude, Voight, Benjamin F, Vollenweider, Peter, Waeber, Gerard, Waterworth, Dawn M, Watkins, Hugh, Wheeler, Eleanor, Widen, Elisabeth, Wild, Sarah H, Willems, Sara M, Willemsen, Gonneke, Wilson, James F, Witteman, Jacqueline C M, Wright, Alan F, Yaghootkar, Hanieh, Zelenika, Diana, Zemunik, Tatijana, Zgaga, Lina, Wareham, Nicholas J, McCarthy, Mark I, Barroso, Ines, Watanabe, Richard M, Florez, Jose C, Dupuis, Josée, Meigs, James B, and Langenberg, Claudia

Published
2012
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22. Characterization of European Ancestry Nonalcoholic Fatty Liver Disease-Associated Variants in Individuals of African And Hispanic Descent

Author

Palmer, Nicholette D., Musani, Solomon K., Yerges-Armstrong, Laura M., Feitosa, Mary F., Bielak, Lawrence F., Hernaez, Ruben, Kahali, Bratati, Carr, Jeffrey J., Harris, Tamara B., Jhun, Min A., Kardia, Sharon L.R., Langefeld, Carl D., Mosley, Thomas H., Jr, Norris, Jill M., Smith, Albert V., Taylor, Herman A., Wagenknecht, Lynne E., Liu, Jiankang, Borecki, Ingrid B., Peyser, Patricia A., and Speliotes, Elizabeth K.

Published
2013
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23. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Kachroo, Priyadarshini, primary, Hecker, Julian, additional, Chawes, Bo L., additional, Ahluwalia, Tarunveer S., additional, Cho, Michael H., additional, Qiao, Dandi, additional, Kelly, Rachel S., additional, Chu, Su H., additional, Virkud, Yamini V., additional, Huang, Mengna, additional, Barnes, Kathleen C., additional, Burchard, Esteban G., additional, Eng, Celeste, additional, Hu, Donglei, additional, Celedón, Juan C., additional, Daya, Michelle, additional, Levin, Albert M., additional, Gui, Hongsheng, additional, Williams, L. Keoki, additional, Forno, Erick, additional, Mak, Angel C.Y., additional, Avila, Lydiana, additional, Soto-Quiros, Manuel E., additional, Cloutier, Michelle M., additional, Acosta-Pérez, Edna, additional, Canino, Glorisa, additional, Bønnelykke, Klaus, additional, Bisgaard, Hans, additional, Raby, Benjamin A., additional, Lange, Christoph, additional, Weiss, Scott T., additional, Lasky-Su, Jessica A., additional, Abe, Namiko, additional, Abecasis, Goncalo, additional, Albert, Christine, additional, Palmer Allred, Nicholette (Nichole), additional, Almasy, Laura, additional, Alonso, Alvaro, additional, Ament, Seth, additional, Anderson, Peter, additional, Anugu, Pramod, additional, Applebaum-Bowden, Deborah, additional, Arking, Dan, additional, Arnett, Donna K., additional, Ashley-Koch, Allison, additional, Aslibekyan, Stella, additional, Assimes, Tim, additional, Auer, Paul, additional, Avramopoulos, Dimitrios, additional, Barnard, John, additional, Barnes, Kathleen, additional, Barr, R. Graham, additional, Barron-Casella, Emily, additional, Beaty, Terri, additional, Becker, Diane, additional, Becker, Lewis, additional, Beer, Rebecca, additional, Begum, Ferdouse, additional, Beitelshees, Amber, additional, Benjamin, Emelia, additional, Bezerra, Marcos, additional, Bielak, Larry, additional, Bis, Joshua, additional, Blackwell, Thomas, additional, Blangero, John, additional, Boerwinkle, Eric, additional, Borecki, Ingrid, additional, Bowler, Russell, additional, Brody, Jennifer, additional, Broeckel, Ulrich, additional, Broome, Jai, additional, Bunting, Karen, additional, Burchard, Esteban, additional, Cardwell, Jonathan, additional, Carty, Cara, additional, Casaburi, Richard, additional, Casella, James, additional, Chaffin, Mark, additional, Chang, Christy, additional, Chasman, Daniel, additional, Chavan, Sameer, additional, Chen, Bo-Juen, additional, Chen, Wei-Min, additional, Chen, Yii-Der Ida, additional, Choi, Seung Hoan, additional, Chuang, Lee-Ming, additional, Chung, Mina, additional, Cornell, Elaine, additional, Correa, Adolfo, additional, Crandall, Carolyn, additional, Crapo, James, additional, Cupples, L. Adrienne, additional, Curran, Joanne, additional, Curtis, Jeffrey, additional, Custer, Brian, additional, Damcott, Coleen, additional, Darbar, Dawood, additional, Das, Sayantan, additional, David, Sean, additional, Davis, Colleen, additional, de Andrade, Mariza, additional, DeBaun, Michael, additional, Deka, Ranjan, additional, DeMeo, Dawn, additional, Devine, Scott, additional, Do, Ron, additional, Duan, Qing, additional, Duggirala, Ravi, additional, Durda, Peter, additional, Dutcher, Susan, additional, Eaton, Charles, additional, Ekunwe, Lynette, additional, Ellinor, Patrick, additional, Emery, Leslie, additional, Farber, Charles, additional, Farnam, Leanna, additional, Fingerlin, Tasha, additional, Flickinger, Matthew, additional, Fornage, Myriam, additional, Franceschini, Nora, additional, Fu, Mao, additional, Fullerton, Stephanie M., additional, Fulton, Lucinda, additional, Gabriel, Stacey, additional, Gan, Weiniu, additional, Gao, Yan, additional, Gass, Margery, additional, Gelb, Bruce, additional, Geng, Xiaoqi (Priscilla), additional, Germer, Soren, additional, Gignoux, Chris, additional, Gladwin, Mark, additional, Glahn, David, additional, Gogarten, Stephanie, additional, Gong, Da-Wei, additional, Goring, Harald, additional, Gu, C. Charles, additional, Guan, Yue, additional, Guo, Xiuqing, additional, Haessler, Jeff, additional, Hall, Michael, additional, Harris, Daniel, additional, Hawley, Nicola, additional, He, Jiang, additional, Heavner, Ben, additional, Heckbert, Susan, additional, Hernandez, Ryan, additional, Herrington, David, additional, Hersh, Craig, additional, Hidalgo, Bertha, additional, Hixson, James, additional, Hokanson, John, additional, Holly, Kramer, additional, Hong, Elliott, additional, Hoth, Karin, additional, (Agnes) Hsiung, Chao, additional, Huston, Haley, additional, Hwu, Chii Min, additional, Irvin, Marguerite Ryan, additional, Jackson, Rebecca, additional, Jain, Deepti, additional, Jaquish, Cashell, additional, Jhun, Min A., additional, Johnsen, Jill, additional, Johnson, Andrew, additional, Johnson, Craig, additional, Johnston, Rich, additional, Jones, Kimberly, additional, Kachroo, Priyadarshini, additional, Kang, Hyun Min, additional, Kaplan, Robert, additional, Kardia, Sharon, additional, Kathiresan, Sekar, additional, Kaufman, Laura, additional, Kelly, Shannon, additional, Kenny, Eimear, additional, Kessler, Michael, additional, Khan, Alyna, additional, Kinney, Greg, additional, Konkle, Barbara, additional, Kooperberg, Charles, additional, Krauter, Stephanie, additional, Lange, Ethan, additional, Lange, Leslie, additional, Laurie, Cathy, additional, Laurie, Cecelia, additional, LeBoff, Meryl, additional, Lee, Seunggeun Shawn, additional, Lee, Wen-Jane, additional, LeFaive, Jonathon, additional, Levine, David, additional, Levy, Dan, additional, Lewis, Joshua, additional, Li, Yun, additional, Lin, Honghuang, additional, Lin, Keng Han, additional, Liu, Simin, additional, Liu, Yongmei, additional, Loos, Ruth, additional, Lubitz, Steven, additional, Lunetta, Kathryn, additional, Luo, James, additional, Mahaney, Michael, additional, Make, Barry, additional, Manichaikul, Ani, additional, Manson, JoAnn, additional, Margolin, Lauren, additional, Martin, Lisa, additional, Mathai, Susan, additional, Mathias, Rasika, additional, McArdle, Patrick, additional, McDonald, Merry-Lynn, additional, McFarland, Sean, additional, McGarvey, Stephen, additional, Mei, Hao, additional, Meyers, Deborah A., additional, Mikulla, Julie, additional, Min, Nancy, additional, Minear, Mollie, additional, Minster, Ryan L., additional, Mitchell, Braxton, additional, Montasser, May E., additional, Musani, Solomon, additional, Mwasongwe, Stanford, additional, Mychaleckyj, Josyf C., additional, Nadkarni, Girish, additional, Naik, Rakhi, additional, Natarajan, Pradeep, additional, Nekhai, Sergei, additional, Nickerson, Deborah, additional, North, Kari, additional, O'Connell, Jeff, additional, O'Connor, Tim, additional, Ochs-Balcom, Heather, additional, Pankow, James, additional, Papanicolaou, George, additional, Parker, Margaret, additional, Parsa, Afshin, additional, Penchev, Sara, additional, Peralta, Juan Manuel, additional, Perez, Marco, additional, Perry, James, additional, Peters, Ulrike, additional, Peyser, Patricia, additional, Phillips, Lawrence S., additional, Phillips, Sam, additional, Pollin, Toni, additional, Post, Wendy, additional, Becker, Julia Powers, additional, Boorgula, Meher Preethi, additional, Preuss, Michael, additional, Prokopenko, Dmitry, additional, Psaty, Bruce, additional, Qasba, Pankaj, additional, Qin, Zhaohui, additional, Rafaels, Nicholas, additional, Raffield, Laura, additional, Ramachandran, Vasan, additional, Rao, D.C., additional, Rasmussen-Torvik, Laura, additional, Ratan, Aakrosh, additional, Redline, Susan, additional, Reed, Robert, additional, Regan, Elizabeth, additional, Reiner, Alex, additional, Rice, Ken, additional, Rich, Stephen, additional, Roden, Dan, additional, Roselli, Carolina, additional, Rotter, Jerome, additional, Ruczinski, Ingo, additional, Russell, Pamela, additional, Ruuska, Sarah, additional, Ryan, Kathleen, additional, Sakornsakolpat, Phuwanat, additional, Salimi, Shabnam, additional, Salzberg, Steven, additional, Sandow, Kevin, additional, Sankaran, Vijay, additional, Scheller, Christopher, additional, Schmidt, Ellen, additional, Schwander, Karen, additional, Schwartz, David, additional, Sciurba, Frank, additional, Seidman, Christine, additional, Seidman, Jonathan, additional, Sheehan, Vivien, additional, Shetty, Amol, additional, Shetty, Aniket, additional, Sheu, Wayne Hui-Heng, additional, Shoemaker, M. Benjamin, additional, Silver, Brian, additional, Silverman, Edwin, additional, Smith, Jennifer, additional, Smith, Josh, additional, Smith, Nicholas, additional, Smith, Tanja, additional, Smoller, Sylvia, additional, Snively, Beverly, additional, Sofer, Tamar, additional, Sotoodehnia, Nona, additional, Stilp, Adrienne, additional, Streeten, Elizabeth, additional, Sung, Yun Ju, additional, Su-Lasky, Jessica, additional, Sylvia, Jody, additional, Szpiro, Adam, additional, Sztalryd, Carole, additional, Taliun, Daniel, additional, Tang, Hua, additional, Taub, Margaret, additional, Taylor, Kent, additional, Taylor, Simeon, additional, Telen, Marilyn, additional, Thornton, Timothy A., additional, Tinker, Lesley, additional, Tirschwell, David, additional, Tiwari, Hemant, additional, Tracy, Russell, additional, Tsai, Michael, additional, Vaidya, Dhananjay, additional, VandeHaar, Peter, additional, Vrieze, Scott, additional, Walker, Tarik, additional, Wallace, Robert, additional, Walts, Avram, additional, Wan, Emily, additional, Wang, Fei Fei, additional, Watson, Karol, additional, Weeks, Daniel E., additional, Weir, Bruce, additional, Weiss, Scott, additional, Weng, Lu-Chen, additional, Willer, Cristen, additional, Williams, Kayleen, additional, Wilson, Carla, additional, Wilson, James, additional, Wong, Quenna, additional, Xu, Huichun, additional, Yanek, Lisa, additional, Yang, Ivana, additional, Yang, Rongze, additional, Zaghloul, Norann, additional, Zekavat, Maryam, additional, Zhang, Yingze, additional, Zhao, Snow Xueyan, additional, Zhao, Wei, additional, Zheng, Xiuwen, additional, Zhi, Degui, additional, Zhou, Xiang, additional, Zody, Michael, additional, and Zoellner, Sebastian, additional

Published
2019
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24. Tissue-Specific Alteration of Metabolic Pathways Influences Glycemic Regulation

Author

Ng, Natasha, primary, Willems, Sara M., additional, Fernandez, Juan, additional, Fine, Rebecca S., additional, Wheeler, Eleanor, additional, Wessel, Jennifer, additional, Kitajima, Hidetoshi, additional, Marenne, Gaëlle, additional, Rundle, Jana K., additional, Sim, Xueling, additional, Yeghootkar, Hanieh, additional, Beer, Nicola L., additional, Raimondo, Anne, additional, Tarasov, Andrei I., additional, Thomsen, Soren K., additional, van de Bunt, Martijn, additional, Wang, Shuai, additional, Chen, Sai, additional, Chen, Yuning, additional, Chen, Yii-Der Ida, additional, de Haan, Hugoline G., additional, Grarup, Niels, additional, Li-Gao, Ruifang, additional, Varga, Tibor V., additional, Asimit, Jennifer L, additional, Feng, Shuang, additional, Strawbridge, Rona J., additional, Kleinbrink, Erica L., additional, Ahluwalia, Tarunveer S., additional, An, Ping, additional, Appel, Emil V., additional, Arking, Dan E, additional, Auvinen, Juha, additional, Bielak, Lawrence F., additional, Bihlmeyer, Nathan A., additional, Bork-Jensen, Jette, additional, Brody, Jennifer A., additional, Campbell, Archie, additional, Chu, Audrey Y, additional, Davies, Gail, additional, Demirkan, Ayse, additional, Floyd, James S., additional, Giulianini, Franco, additional, Guo, Xiuqing, additional, Gustafsson, Stefan, additional, Hastoy, Benoit, additional, Jackson, Anne U., additional, Jakobsdottir, Johanna, additional, Järvelin, Marjo-Riitta, additional, Jensen, Richard A., additional, Kanoni, Stavroula, additional, Keinanen-Kiukaanniemi, Sirkka, additional, Li, Jin, additional, Li, Man, additional, Lohman, Kurt, additional, Lu, Yingchang, additional, Luan, Jian’an, additional, Manning, Alisa K., additional, Marten, Jonathan, additional, Marzi, Carola, additional, Meidtner, Karina, additional, Mook-Kanamori, Dennis O., additional, Muka, Taulant, additional, Pistis, Giorgio, additional, Prins, Bram, additional, Rice, Kenneth M., additional, Robertson, Neil, additional, Sanna, Serena, additional, Shi, Yuan, additional, Smith, Albert Vernon, additional, Smith, Jennifer A., additional, Southam, Lorraine, additional, Stringham, Heather M., additional, Tajuddin, Salman M., additional, Tragante, Vinicius, additional, van der Laan, Sander W., additional, Warren, Helen R., additional, Yao, Jie, additional, Yiorkas, Andrianos M., additional, Zhang, Weihua, additional, Zhao, Wei, additional, Ahlqvist, Emma, additional, Graff, Mariaelisa, additional, Highland, Heather M., additional, Justice, Anne E., additional, Lo, Ken Sin, additional, Marouli, Eirini, additional, Medina-Gomez, Carolina, additional, Afaq, Saima, additional, Alhejily, Wesam A., additional, Amin, Najaf, additional, Asselbergs, Folkert W., additional, Bonnycastle, Lori L., additional, Bots, Michiel L., additional, Brandslund, Ivan, additional, Chen, Ji, additional, Christensen, Cramer, additional, Danesh, John, additional, de Mutsert, Renée, additional, Dehghan, Abbas, additional, Ebeling, Tapani, additional, Elliott, Paul, additional, Consortium, EPIC-InterAct, additional, Farmaki, Aliki-Eleni, additional, Faul, Jessica D., additional, Franks, Paul W., additional, Franks, Steve, additional, Fritsche, Andreas, additional, Gjesing, Anette P., additional, Goodarzi, Mark O., additional, Gudnason, Vilmundur, additional, Hallmans, Göran, additional, Harris, Tamara B., additional, Herzig, Karl-Heinz, additional, Hivert, Marie-France, additional, Jansson, Jan-Håkan, additional, Jhun, Min A., additional, Beck Jørgensen, Torben, additional, Jørgensen, Marit E., additional, Jousilahti, Pekka, additional, Kajantie, Eero, additional, Karaleftheri, Maria, additional, Kardia, Sharon L.R., additional, Kinnunen, Leena, additional, Koistinena, Heikki A., additional, Komulainen, Pirjo, additional, Kovacs, Peter, additional, Kuusisto, Johanna, additional, Laakso, Markku, additional, Lange, Leslie A., additional, Launer, Lenore J., additional, Lee, Jung-Jin, additional, Leong, Aaron, additional, Lindström, Jaana, additional, Fox, Jocelyn E. Manning, additional, Männistö, Satu, additional, Maruthur, Nisa M., additional, Moilanen, Leena, additional, Mulas, Antonella, additional, Nalls, Mike A., additional, Neville, Matthew, additional, Pankow, James S., additional, Pattie, Alison, additional, Petersen, Eva R. B., additional, Puolijoki, Hannu, additional, Rasheed, Asif, additional, Redmond, Paul, additional, Renström, Frida, additional, Roden, Michael, additional, Saleheen, Danish, additional, Saltevo, Juha, additional, Savonen, Kai, additional, Sébert, Sylvain P., additional, Skaaby, Tea, additional, Small, Kerrin S., additional, Stančáková, Alena, additional, Stokholm, Jakob, additional, Strauch, Konstantin, additional, Tai, E-Shyong, additional, Taylor, Kent D., additional, Thuesen, Betina H., additional, Tönjes, Anke, additional, Tsafantakis, Emmanouil, additional, Tuomi, Tiinamaija, additional, Tuomilehto, Jaakko, additional, Group, Understanding Society Scientific, additional, Uusitupa, Matti I., additional, Vääräsmäki, Marja, additional, Vaartjes, Ilonca, additional, Zoledziewska, Magdalena, additional, Abecasis, Goncalo, additional, Balkau, Beverley, additional, Bisgaard, Hans, additional, Blakemore, Alexandra I., additional, Blüher, Matthias, additional, Boeing, Heiner, additional, Boerwinkle, Eric, additional, Bønnelykke, Klaus, additional, Bottinger, Erwin P., additional, Caulfield, Mark J., additional, Chambers, John C., additional, Chasman, Daniel I., additional, Cheng, Ching-Yu, additional, Clark, Anne, additional, Collins, Francis S., additional, Coresh, Josef, additional, Cucca, Francesco, additional, de Borst, Gert J., additional, Deary, Ian J., additional, Dedoussis, George, additional, Deloukas, Panos, additional, den Ruijter, Hester M., additional, Dupuis, Josée, additional, Evans, Michele K., additional, Ferrannini, Ele, additional, Franco, Oscar H., additional, Grallert, Harald, additional, Groop, Leif, additional, Hansen, Torben, additional, Hattersley, Andrew T., additional, Hayward, Caroline, additional, Hirschhorn, Joel N., additional, Ikram, M. Arfan, additional, Ingelsson, Erik, additional, Karpe, Fredrik, additional, Kaw, Kay-Tee, additional, Kiess, Wieland, additional, Kooner, Jaspal S., additional, Körner, Antje, additional, Lakka, Timo, additional, Langenberg, Claudia, additional, Lind, Lars, additional, Lindgren, Cecilia M., additional, Linneberg, Allan, additional, Lipovich, Leonard, additional, Liu, Ching-Ti, additional, Liu, Jun, additional, Liu, Yongmei, additional, Loos, Ruth J. F., additional, MacDonald, Patrick E., additional, Mohlke, Karen L., additional, Morris, Andrew D., additional, Munroe, Patricia B., additional, Murray, Alison, additional, Padmanabhan, Sandosh, additional, Palmer, Colin N. A., additional, Pasterkamp, Gerard, additional, Pedersen, Oluf, additional, Peyser, Patricia A., additional, Polasek, Ozren, additional, Porteous, David, additional, Province, Michael A., additional, Psaty, Bruce M., additional, Rauramaa, Rainer, additional, Ridker, Paul M., additional, Rolandsson, Olov, additional, Rorsman, Patrik, additional, Rosendaal, Frits, additional, Rudan, Igor, additional, Salomaa, Veikko, additional, Schulze, Matthias B., additional, Sladek, Robert, additional, Smith, Blair H., additional, Spector, Timothy D., additional, Starr, John M., additional, Stumvoll, Michael, additional, van Duijn, Cornelia M., additional, Walker, Mark, additional, Wareham, Nick J., additional, Weir, David R., additional, Wilson, James G., additional, Wong, Tien Yin, additional, Zeggini, Eleftheria, additional, Zonderman, Alan B., additional, Rotter, Jerome I., additional, Morris, Andrew P., additional, Boehnke, Michael, additional, Florez, Jose, additional, McCarthy, Mark I., additional, Meigs, James B., additional, Mahajan, Anubha, additional, Scott, Robert A., additional, Gloyn, Anna L., additional, and Barroso, Ines, additional

Published
2019
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25. DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases

Author

Ligthart, Symen, Marzi, Carola, Aslibekyan, Stella, Mendelson, Michael M, Conneely, Karen N, Tanaka, Toshiko, Colicino, Elena, Waite, Lindsay L, Joehanes, Roby, Guan, Weihua, Brody, Jennifer A, Elks, Cathy, Marioni, Riccardo, Jhun, Min A, Agha, Golareh, Bressler, Jan, Ward-Caviness, Cavin K, Chen, Brian H, Huan, Tianxiao, Bakulski, Kelly, Salfati, Elias L, WHI-EMPC Investigators, Fiorito, Giovanni, CHARGE epigenetics of Coronary Heart Disease, Wahl, Simone, Schramm, Katharina, Sha, Jin, Hernandez, Dena G, Just, Allan C, Smith, Jennifer A, Sotoodehnia, Nona, Pilling, Luke C, Pankow, James S, Tsao, Phil S, Liu, Chunyu, Zhao, Wei, Guarrera, Simonetta, Michopoulos, Vasiliki J, Smith, Alicia K, Peters, Marjolein J, Melzer, David, Vokonas, Pantel, Fornage, Myriam, Prokisch, Holger, Bis, Joshua C, Chu, Audrey Y, Herder, Christian, Grallert, Harald, Yao, Chen, Shah, Sonia, McRae, Allan F, Lin, Honghuang, Horvath, Steve, Fallin, Daniele, Hofman, Albert, Wareham, Nicholas J, Wiggins, Kerri L, Feinberg, Andrew P, Starr, John M, Visscher, Peter M, Murabito, Joanne M, Kardia, Sharon LR, Absher, Devin M, Binder, Elisabeth B, Singleton, Andrew B, Bandinelli, Stefania, Peters, Annette, Waldenberger, Melanie, Matullo, Giuseppe, Schwartz, Joel D, Demerath, Ellen W, Uitterlinden, André G, van Meurs, Joyce BJ, Franco, Oscar H, Chen, Yii-Der Ida, Levy, Daniel, Turner, Stephen T, Deary, Ian J, Ressler, Kerry J, Dupuis, Josée, Ferrucci, Luigi, Ong, Ken K, Assimes, Themistocles L, Boerwinkle, Eric, Koenig, Wolfgang, Arnett, Donna K, Baccarelli, Andrea A, Benjamin, Emelia J, Dehghan, Abbas, Wareham, Nicholas [0000-0003-1422-2993], Ong, Kenneth [0000-0003-4689-7530], and Apollo - University of Cambridge Repository

Subjects
Male, Inflammation, DNA methylation, Quantitative Trait Loci, Diabetes, Gene Expression, Genetic Variation, White People, Epigenesis, Genetic, C-reactive protein, Black or African American, Coronary heart disease, Epigenome-wide association study, Humans, CpG Islands, Female, Nucleotide Motifs, Body mass index, Genome-Wide Association Study
Abstract

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P –7) in the discovery panel of European ancestry and replicated (P –4) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (P –5), ten (17%) CpG sites were associated with a nearby genetic variant (P –3), and 51 (88%) were also associated with at least one related cardiometabolic entity (P –5). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants.Conclusion: We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation.

Published
2016

26. Novel DNA methylation sites of glucose and insulin homeostasis: an integrative cross-omics analysis

Author

Liu, Jun, primary, Carnero-Montoro, Elena, additional, van Dongen, Jenny, additional, Lent, Samantha, additional, Nedeljkovic, Ivana, additional, Ligthart, Symen, additional, Tsai, Pei-Chien, additional, Martin, Tiphaine C., additional, Mandaviya, Pooja R., additional, Jansen, Rick, additional, Peters, Marjolein J., additional, Duijts, Liesbeth, additional, Jaddoe, Vincent W.V., additional, Tiemeier, Henning, additional, Felix, Janine F., additional, Chu, Audrey Y., additional, Levy, Daniel, additional, Hwang, Shih-Jen, additional, Bressler, Jan, additional, Gondalia, Rahul, additional, Salfati, Elias L., additional, Herder, Christian, additional, Hidalgo, Bertha A., additional, Tanaka, Toshiko, additional, Moore, Ann Zenobia, additional, Lemaitre, Rozenn N., additional, Jhun, Min A., additional, Smith, Jennifer A., additional, Sotoodehnia, Nona, additional, Bandinelli, Stefania, additional, Ferrucci, Luigi, additional, Arnett, Donna K., additional, Grallert, Harald, additional, Assimes, Themistocles L., additional, Hou, Lifang, additional, Baccarelli, Andrea, additional, Whitsel, Eric A., additional, van Dijk, Ko Willems, additional, Amin, Najaf, additional, Uitterlinden, André G., additional, Sijbrands, Eric J.G., additional, Franco, Oscar H., additional, Dehghan, Abbas, additional, Spector, Tim D., additional, Dupuis, Josée, additional, Hivert, Marie-France, additional, Rotter, Jerome I., additional, Meigs, James B., additional, Pankow, James S., additional, van Meurs, Joyce B.J., additional, Isaacs, Aaron, additional, Boomsma, Dorret I., additional, Bell, Jordana T., additional, Demirkan, Ayşe, additional, and van Duijn, Cornelia M., additional

Published
2018
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27. O3‐03‐03: EPIGENOME‐WIDE ASSOCIATION STUDIES IMPLICATE GENES INVOLVED IN GLIAL CELL FUNCTION AND VIRAL RESPONSE IN CEREBRAL WHITE MATTER HYPERINTENSITIES

Author

Fornage, Myriam, primary, Adams, Hieab H.H., additional, Bis, Joshua C., additional, Boerwinkle, Eric, additional, Deary, Ian J., additional, Grabe, Hans J., additional, Hou, Lifang, additional, Ikram, M. Arfan, additional, Jhun, Min A., additional, Launer, Lenore J., additional, Luciano, Michelle, additional, Seshadri, Sudha, additional, Smith, Jennifer A., additional, Sotoodehnia, Nona, additional, Teumer, Alexander, additional, and Yang, Qiong, additional

Published
2018
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29. Genome-wide physical activity interactions in adiposity : A meta-analysis of 200,452 adults.

Author

Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, Kilpeläinen, Tuomas O, Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, Faul, Jessica D, Fu, Mao, Færch, Kristine, Gieger, Christian, Gläser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D, Havulinna, Aki S, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Holmens, Oddgeir L, Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kähönen, Nina, James, Alan L, Jansson, John-Olov, Jhun, Min A, Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A, Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaløy, Kirsti, Kähönen, Mika, Lakka, Timo A, Launer, Lenore J, Lehne, Benjamin, Lindgren, Cecilia M, Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L, Montgomery, Grant W, De Moor, Marleen H M, Mulas, Antonella, Müller-Nurasyid, Martina, Musk, A W, Männikkö, Reija, Männistö, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A, Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T, Rankinen, Tuomo, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Ridker, Paul M, Rose, Lynda M, Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A, Savonen, Kai, Scott, William R, Sanna, Serena, Shuldiner, Alan R, Sidney, Steve, Silbernagel, Günther, Smith, Blair H, Smith, Jennifer A, Snieder, Harold, Stančáková, Alena, Sternfeld, Barbara, Swift, Amy J, Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothée, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V, Vohl, Marie-Claude, Völker, Uwe, Waeber, Gérard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F, Zillikens, M Carola, Zubair, Niha, Haiman, Christopher A, Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, André G, Pérusse, Louis, Wilson, James F, Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A, Tönjes, Anke, Bandinelli, Stefania, Palmer, Lyle J, Kardia, Sharon L R, Rauramaa, Rainer, Sørensen, Thorkild I A, Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W J H, de Geus, Eco J C, Boomsma, Dorret I, Lehtimäki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G, Kuh, Diana, Liu, Yongmei, Linneberg, Allan, März, Winfried, Strauch, Konstantin, Kivimäki, Mika, Harris, Tamara B, Gudnason, Vilmundur, Völzke, Henry, Qi, Lu, Järvelin, Marjo-Riitta, Chambers, John C, Kooner, Jaspal S, Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J, Langenberg, Claudia, Weir, David R, Porteous, David J, Boerwinkle, Eric, Chasman, Daniel I, Abecasis, Gonçalo R, Barroso, Inês, McCarthy, Mark I, Frayling, Timothy M, O'Connell, Jeffrey R, van Duijn, Cornelia M, Boehnke, Michael, Heid, Iris M, Mohlke, Karen L, Strachan, David P, Fox, Caroline S, Liu, Ching-Ti, Hirschhorn, Joel N, Klein, Robert J, Johnson, Andrew D, Borecki, Ingrid B, Franks, Paul W, North, Kari E, Cupples, L Adrienne, Loos, Ruth J F, and Kilpeläinen, Tuomas O

Abstract

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery., Correction in: PLOS Genetics, Vol. 13, nr 8, s. e1006972DOI: 10.1371/journal.pgen.1006972

Published
2017
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30. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, Cupples, L Adrienne, Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, and Cupples, L Adrienne

Abstract

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

Published
2017
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31. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

Justice, Anne E., Winkler, Thomas W., Feitosa, Mary F., Graff, Misa, Fisher, Virginia A., Young, Kristin L, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S., Ahluwalia, Tarunveer S., Chu, Audrey Y, Heard-Costa, Nancy L., Lim, Elise, Perez, Jeremiah, Eicher, John D., Kutalik, Zolta'n, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph C., Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F., Bonnefond, Amelie, Bragg-Gresham, Jennifer L., Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Harder, Marie Neergaard, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E., Jackson, Anne U., Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E., Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Müller-Nurasyid, Martina, Navarro, Pau, Pe'russe, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A., Stanča'kova, Alena, Strawbridge, Rona J., Stringham, Heather M., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Van Der Laan, Sander W., van der Most, Peter J., Van Vliet-Ostaptchouk, Jana V., Vedantam, Sailaja L., Verweij, Niek, Vink, Jacqueline M., Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Zhao, Jing Hua, Zimmermann, Martina E., Zubair, Niha, Abecasis, Gonçalo R., Adair, Linda S., Afaq, Saima, Afzal, Uzma, Bakker, Stephan J. L., Bartz, Traci M., Beilby, John, Bergman, Richard N., Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L., Bottinger, Erwin P., Braga, Daniele, Buckley, Brendan M., Buyske, Steve, Campbell, Harry, Chambers, John C., Collins, Francis S., Curran, Joanne E., De Borst, Gert J., De Craen, Anton J M, de Geus, Eco J. C., Dedoussis, George, Delgado, Graciela E., Den Ruijter, Hester M., Eiriksdottir, Gudny, Eriksson, Anna L., Esko, Toñu, Faul, Jessica D., Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas D., Heath, Andrew C., Hernandez, Dena G., Hindorff, Lucia A., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Hottenga, Jouke-Jan, Huang, Jie, Hung, Joseph, Hutri-Kähönen, Nina, Ingelsson, Erik, James, Alan L., Jansson, John Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E., Juonala, Markus, Kähönen, Mika, Karlsson, Magnus, Koistinen, Heikki A., Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Krämer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lee, Nanette R., Lind, Lars, Lindgren, Cecilia M., Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A. F., Männikkö, Reija, Marques-Vidal, Pedro, Martin, Nicholas G., McKenzie, Colin A., McKnight, Barbara, Mellström, Dan, Menni, Cristina, Montgomery, Grant W., Musk, Arthur W., Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Peyser, Patricia A., Pisinger, Charlotta, Porteous, David J., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rasmussen-Torvik, Laura J., Rawal, Rajesh, Rice, Treva K., Ridker, Paul M., Rose, Lynda M., Bien, Stephanie A., Rudan, Igor, Sanna, Serena, Sarzynski, Mark A., Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A., Sennblad, Bengt, Siemelink, Marten A., Silbernagel, Günther, Slagboom, P. Eline, Snieder, Harold, Staessen, Jan A., Stott, David J., Swertz, Morris A., Swift, Amy J., Taylor, Kent D., Tayo, Bamidele O., Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Völzke, Henry, Vonk, Judith M., Waeber, Ge'rard, Waldenberger, Melanie, Westendorp, Rudi G. J., Wild, Sarah H., Willemsen, Gonneke, Wolffenbuttel, Bruce H.R., Wong, Andrew, Wright, Alan F., Zhao, Wei, Zillikens, M. Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Böger, Carsten A, Boomsma, Dorret I., Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I., Ida Chen, Yii Der, Chines, Peter S., Cooper, Richard S., Cucca, Francesco, Cusi, Daniele, de Faire, Ulf, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans Jörgen, Gudnason, Vilmundur, Haiman, Christopher A., Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D., Jukema, J. Wouter, Kardia, Sharon L. R., Kivimaki, Mika, Kooner, Jaspal S., Kuh, Diana, Laakso, Markku, Lehtimäki, Terho, Le Marchand, Loic, März, Winfried, McCarthy, Mark I., Metspalu, Andres, Morris, Andrew P., Ohlsson, Claes, Palmer, Lyle J., Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M., Qi, Lu, Rauramaa, Rainer, Smith, Blair H., Sorensen, Thorkild I. A., Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J., Weir, David R., Whitfield, John B., Wilson, James F., Tyrrell, Jessica, Frayling, Timothy M., Barroso, Inês, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S., Hirschhorn, Joel N., Hunter, David J., Spector, Tim D., Strachan, David P., Van Duijn, Cornelia M., Heid, Iris M., Mohlke, Karen L., Marchini, Jonathan, Loos, Ruth J. F., Kilpeläinen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B., North, Kari E., Cupples, L. Adrienne, Justice, Anne E., Winkler, Thomas W., Feitosa, Mary F., Graff, Misa, Fisher, Virginia A., Young, Kristin L, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S., Ahluwalia, Tarunveer S., Chu, Audrey Y, Heard-Costa, Nancy L., Lim, Elise, Perez, Jeremiah, Eicher, John D., Kutalik, Zolta'n, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph C., Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F., Bonnefond, Amelie, Bragg-Gresham, Jennifer L., Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Harder, Marie Neergaard, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E., Jackson, Anne U., Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E., Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Müller-Nurasyid, Martina, Navarro, Pau, Pe'russe, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A., Stanča'kova, Alena, Strawbridge, Rona J., Stringham, Heather M., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Van Der Laan, Sander W., van der Most, Peter J., Van Vliet-Ostaptchouk, Jana V., Vedantam, Sailaja L., Verweij, Niek, Vink, Jacqueline M., Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Zhao, Jing Hua, Zimmermann, Martina E., Zubair, Niha, Abecasis, Gonçalo R., Adair, Linda S., Afaq, Saima, Afzal, Uzma, Bakker, Stephan J. L., Bartz, Traci M., Beilby, John, Bergman, Richard N., Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L., Bottinger, Erwin P., Braga, Daniele, Buckley, Brendan M., Buyske, Steve, Campbell, Harry, Chambers, John C., Collins, Francis S., Curran, Joanne E., De Borst, Gert J., De Craen, Anton J M, de Geus, Eco J. C., Dedoussis, George, Delgado, Graciela E., Den Ruijter, Hester M., Eiriksdottir, Gudny, Eriksson, Anna L., Esko, Toñu, Faul, Jessica D., Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas D., Heath, Andrew C., Hernandez, Dena G., Hindorff, Lucia A., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Hottenga, Jouke-Jan, Huang, Jie, Hung, Joseph, Hutri-Kähönen, Nina, Ingelsson, Erik, James, Alan L., Jansson, John Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E., Juonala, Markus, Kähönen, Mika, Karlsson, Magnus, Koistinen, Heikki A., Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Krämer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lee, Nanette R., Lind, Lars, Lindgren, Cecilia M., Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A. F., Männikkö, Reija, Marques-Vidal, Pedro, Martin, Nicholas G., McKenzie, Colin A., McKnight, Barbara, Mellström, Dan, Menni, Cristina, Montgomery, Grant W., Musk, Arthur W., Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Peyser, Patricia A., Pisinger, Charlotta, Porteous, David J., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rasmussen-Torvik, Laura J., Rawal, Rajesh, Rice, Treva K., Ridker, Paul M., Rose, Lynda M., Bien, Stephanie A., Rudan, Igor, Sanna, Serena, Sarzynski, Mark A., Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A., Sennblad, Bengt, Siemelink, Marten A., Silbernagel, Günther, Slagboom, P. Eline, Snieder, Harold, Staessen, Jan A., Stott, David J., Swertz, Morris A., Swift, Amy J., Taylor, Kent D., Tayo, Bamidele O., Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Völzke, Henry, Vonk, Judith M., Waeber, Ge'rard, Waldenberger, Melanie, Westendorp, Rudi G. J., Wild, Sarah H., Willemsen, Gonneke, Wolffenbuttel, Bruce H.R., Wong, Andrew, Wright, Alan F., Zhao, Wei, Zillikens, M. Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Böger, Carsten A, Boomsma, Dorret I., Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I., Ida Chen, Yii Der, Chines, Peter S., Cooper, Richard S., Cucca, Francesco, Cusi, Daniele, de Faire, Ulf, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans Jörgen, Gudnason, Vilmundur, Haiman, Christopher A., Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D., Jukema, J. Wouter, Kardia, Sharon L. R., Kivimaki, Mika, Kooner, Jaspal S., Kuh, Diana, Laakso, Markku, Lehtimäki, Terho, Le Marchand, Loic, März, Winfried, McCarthy, Mark I., Metspalu, Andres, Morris, Andrew P., Ohlsson, Claes, Palmer, Lyle J., Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M., Qi, Lu, Rauramaa, Rainer, Smith, Blair H., Sorensen, Thorkild I. A., Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J., Weir, David R., Whitfield, John B., Wilson, James F., Tyrrell, Jessica, Frayling, Timothy M., Barroso, Inês, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S., Hirschhorn, Joel N., Hunter, David J., Spector, Tim D., Strachan, David P., Van Duijn, Cornelia M., Heid, Iris M., Mohlke, Karen L., Marchini, Jonathan, Loos, Ruth J. F., Kilpeläinen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B., North, Kari E., and Cupples, L. Adrienne

Published
2017

32. DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation

Author

Richard, Melissa A., Richard, Melissa A., Huan, Tianxiao, Ligthart, Symen, Gondalia, Rahul, Jhun, Min A., Brody, Jennifer A., Irvin, Marguerite R., Marioni, Riccardo, Shen, Jincheng, Tsai, Pei-Chien, Montasser, May E., Jia, Yucheng, Syme, Catriona, Salfati, Elias L., Boerwinkle, Eric, Guan, Weihua, Mosley, Thomas H., Bressler, Jan, Morrison, Alanna C., Liu, Chunyu, Mendelson, Michael M., Uitterlinden, Andre G., van Meurs, Joyce B., Franco, Oscar H., Zhang, Guosheng, Li, Yun, Stewart, James D., Bis, Joshua C., Psaty, Bruce M., Chen, Yii-Der Ida, Kardia, Sharon L. R., Zhao, Wei, Turner, Stephen T., Absher, Devin, Aslibekyan, Stella, Starr, John M., Mcrae, Allan F., Hou, Lifang, Just, Allan C., Schwartz, Joel D., Vokonas, Pantel S., Menni, Cristina, Spector, Tim D., Shuldiner, Alan, Damcott, Coleen M., Rotter, Jerome I., BIOS Consortium, van Greevenbroek, Marleen, Stehouwer, Coen, van der Kallen, Carla, Schalkwijk, Casper, Fornage, Myriam, Richard, Melissa A., Richard, Melissa A., Huan, Tianxiao, Ligthart, Symen, Gondalia, Rahul, Jhun, Min A., Brody, Jennifer A., Irvin, Marguerite R., Marioni, Riccardo, Shen, Jincheng, Tsai, Pei-Chien, Montasser, May E., Jia, Yucheng, Syme, Catriona, Salfati, Elias L., Boerwinkle, Eric, Guan, Weihua, Mosley, Thomas H., Bressler, Jan, Morrison, Alanna C., Liu, Chunyu, Mendelson, Michael M., Uitterlinden, Andre G., van Meurs, Joyce B., Franco, Oscar H., Zhang, Guosheng, Li, Yun, Stewart, James D., Bis, Joshua C., Psaty, Bruce M., Chen, Yii-Der Ida, Kardia, Sharon L. R., Zhao, Wei, Turner, Stephen T., Absher, Devin, Aslibekyan, Stella, Starr, John M., Mcrae, Allan F., Hou, Lifang, Just, Allan C., Schwartz, Joel D., Vokonas, Pantel S., Menni, Cristina, Spector, Tim D., Shuldiner, Alan, Damcott, Coleen M., Rotter, Jerome I., BIOS Consortium, van Greevenbroek, Marleen, Stehouwer, Coen, van der Kallen, Carla, Schalkwijk, Casper, and Fornage, Myriam

Abstract

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p <1.0 x 10(-7); replication: N = 7,182, p <1.6 x 10(-3)). The replicated methylation sites are heritable (h(2) > 30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.

Published
2017

33. SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function

Author

Li, Man, Li, Yong, Weeks, Olivia, Mijatovic, Vladan, Teumer, Alexander, Huffman, Jennifer E., Tromp, Gerard, Fuchsberger, Christian, Gorski, Mathias, Lyytikainen, Leo-Pekka, Nutile, Teresa, Sedaghat, Sanaz, Sorice, Rossella, Tin, Adrienne, Yang, Qiong, Ahluwalia, Tarunveer S., Arking, Dan E., Bihlmeyer, Nathan A., Boeger, Carsten A., Carroll, Robert J., Chasman, Daniel I., Comelis, Marilyn C., Dehghan, Abbas, Faul, Jessica D., Feitosa, Mary F., Gambaro, Giovanni, Gasparini, Paolo, Giulianini, Franco, Heid, Iris, Huang, Jinyan, Imboden, Medea, Jackson, Anne U., Jeff, Janina, Jhun, Min A., Katz, Ronit, Kifley, Annette, Kilpelainen, Tuomas, Kumar, Ashish, Laakso, Markku, Li-Gao, Ruifang, Lohman, Kurt, Lu, Yingchang, Maegi, Reedik, Malerba, Giovanni, Mihailov, Evelin, Mohlke, Karen L., Mook-Kanamori, Dennis O., Robino, Antonietta, Ruderfer, Douglas, Salvi, Erika, Schick, Ursula M., Schulz, Christina-Alexandra, Smith, Albert V., Smith, Jennifer A., Traglia, Michela, Yerges-Armstrong, Laura M., Zhao, Wei, Goodarzi, Mark O., Kraja, Aldi T., Liu, Chunyu, Wessel, Jennifer, Boerwinkle, Eric, Borecki, Ingrid B., Bork-Jensen, Jette, Bottinger, Erwin P., Braga, Daniele, Brandslund, Ivan, Brody, Jennifer A., Campbell, Archie, Carey, David J., Christensen, Cramer, Coresh, Josef, Crook, Errol, Curhan, Gary C., Cusi, Daniele, de Boer, Ian H., de Vries, Aiko P. J., Denny, Joshua C., Devuyst, Olivier, Dreisbach, Albert W., Endlich, Karlhans, Esko, Tonu, Franco, Oscar H., Fulop, Tibor, Gerhard, Glenn S., Gluemer, Charlotte, Gottesman, Omri, Grarup, Niels, Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B., Hayward, Caroline, Hocking, Lynne, Hofman, Albert, Hu, Frank B., Husemoen, Lise Lotte N., Jackson, Rebecca D., Jorgensen, Torben, Jorgensen, Marit E., Kaehoenen, Mika, Kardia, Sharon L. R., Koenig, Wolfgang, Kooperberg, Charles, Kriebel, Jennifer, Launer, Lenore J., Lauritzen, Torsten, Lehtimaki, Terho, Levy, Daniel, Linksted, Pamela, Linneberg, Allan, Liu, Yongmei, Loos, Ruth J. F., Lupo, Antonio, Meisinger, Christine, Melander, Olle, Metspalu, Andres, Mitchell, Paul, Nauck, Matthias, Nuernberg, Peter, Orho-Melander, Marju, Parsa, Afshin, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Porteous, David, Probst-Hensch, Nicole M., Psaty, Bruce M., Qi, Lu, Raitakari, Olli T., Reiner, Alex P., Rettig, Rainer, Ridker, Paul M., Rivadeneira, Fernando, Rossouw, Jacques E., Schmidt, Frank, Siscovick, David, Soranzo, Nicole, Strauch, Konstantin, Toniolo, Daniela, Turner, Stephen T., Uitterlinden, Andre G., Ulivi, Sheila, Velayutham, Dinesh, Voelker, Uwe, Volzke, Henry, Waldenberger, Melanie, Wang, Jie Jin, Weir, David R., Witte, Daniel, Kuivaniemi, Helena, Fox, Caroline S., Franceschini, Nora, Goessling, Wolfram, Koettgen, Anna, Chu, Audrey Y., Li, Man, Li, Yong, Weeks, Olivia, Mijatovic, Vladan, Teumer, Alexander, Huffman, Jennifer E., Tromp, Gerard, Fuchsberger, Christian, Gorski, Mathias, Lyytikainen, Leo-Pekka, Nutile, Teresa, Sedaghat, Sanaz, Sorice, Rossella, Tin, Adrienne, Yang, Qiong, Ahluwalia, Tarunveer S., Arking, Dan E., Bihlmeyer, Nathan A., Boeger, Carsten A., Carroll, Robert J., Chasman, Daniel I., Comelis, Marilyn C., Dehghan, Abbas, Faul, Jessica D., Feitosa, Mary F., Gambaro, Giovanni, Gasparini, Paolo, Giulianini, Franco, Heid, Iris, Huang, Jinyan, Imboden, Medea, Jackson, Anne U., Jeff, Janina, Jhun, Min A., Katz, Ronit, Kifley, Annette, Kilpelainen, Tuomas, Kumar, Ashish, Laakso, Markku, Li-Gao, Ruifang, Lohman, Kurt, Lu, Yingchang, Maegi, Reedik, Malerba, Giovanni, Mihailov, Evelin, Mohlke, Karen L., Mook-Kanamori, Dennis O., Robino, Antonietta, Ruderfer, Douglas, Salvi, Erika, Schick, Ursula M., Schulz, Christina-Alexandra, Smith, Albert V., Smith, Jennifer A., Traglia, Michela, Yerges-Armstrong, Laura M., Zhao, Wei, Goodarzi, Mark O., Kraja, Aldi T., Liu, Chunyu, Wessel, Jennifer, Boerwinkle, Eric, Borecki, Ingrid B., Bork-Jensen, Jette, Bottinger, Erwin P., Braga, Daniele, Brandslund, Ivan, Brody, Jennifer A., Campbell, Archie, Carey, David J., Christensen, Cramer, Coresh, Josef, Crook, Errol, Curhan, Gary C., Cusi, Daniele, de Boer, Ian H., de Vries, Aiko P. J., Denny, Joshua C., Devuyst, Olivier, Dreisbach, Albert W., Endlich, Karlhans, Esko, Tonu, Franco, Oscar H., Fulop, Tibor, Gerhard, Glenn S., Gluemer, Charlotte, Gottesman, Omri, Grarup, Niels, Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B., Hayward, Caroline, Hocking, Lynne, Hofman, Albert, Hu, Frank B., Husemoen, Lise Lotte N., Jackson, Rebecca D., Jorgensen, Torben, Jorgensen, Marit E., Kaehoenen, Mika, Kardia, Sharon L. R., Koenig, Wolfgang, Kooperberg, Charles, Kriebel, Jennifer, Launer, Lenore J., Lauritzen, Torsten, Lehtimaki, Terho, Levy, Daniel, Linksted, Pamela, Linneberg, Allan, Liu, Yongmei, Loos, Ruth J. F., Lupo, Antonio, Meisinger, Christine, Melander, Olle, Metspalu, Andres, Mitchell, Paul, Nauck, Matthias, Nuernberg, Peter, Orho-Melander, Marju, Parsa, Afshin, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Porteous, David, Probst-Hensch, Nicole M., Psaty, Bruce M., Qi, Lu, Raitakari, Olli T., Reiner, Alex P., Rettig, Rainer, Ridker, Paul M., Rivadeneira, Fernando, Rossouw, Jacques E., Schmidt, Frank, Siscovick, David, Soranzo, Nicole, Strauch, Konstantin, Toniolo, Daniela, Turner, Stephen T., Uitterlinden, Andre G., Ulivi, Sheila, Velayutham, Dinesh, Voelker, Uwe, Volzke, Henry, Waldenberger, Melanie, Wang, Jie Jin, Weir, David R., Witte, Daniel, Kuivaniemi, Helena, Fox, Caroline S., Franceschini, Nora, Goessling, Wolfram, Koettgen, Anna, and Chu, Audrey Y.

Abstract

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (n(stage1);111,666;n(stage2): 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; P-stage1<3.7 x10(-7)), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4x 10(-8) by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

Published
2017

34. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

UMC Utrecht, Experimentele Afd. Cardiologie 1, Circulatory Health, In Vivo NMR ISI, Verpleegafd Vaatchirurgie D4 Oost, Onderzoek Vrouw Hart & Vaatziekten, Justice, Anne E., Winkler, Thomas W., Feitosa, Mary F., Graff, Misa, Fisher, Virginia A., Young, Kristin L, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S., Ahluwalia, Tarunveer S., Chu, Audrey Y, Heard-Costa, Nancy L., Lim, Elise, Perez, Jeremiah, Eicher, John D., Kutalik, Zolta'n, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph C., Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F., Bonnefond, Amelie, Bragg-Gresham, Jennifer L., Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Harder, Marie Neergaard, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E., Jackson, Anne U., Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E., Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Müller-Nurasyid, Martina, Navarro, Pau, Pe'russe, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A., Stanča'kova, Alena, Strawbridge, Rona J., Stringham, Heather M., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Van Der Laan, Sander W., van der Most, Peter J., Van Vliet-Ostaptchouk, Jana V., Vedantam, Sailaja L., Verweij, Niek, Vink, Jacqueline M., Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Zhao, Jing Hua, Zimmermann, Martina E., Zubair, Niha, Abecasis, Gonçalo R., Adair, Linda S., Afaq, Saima, Afzal, Uzma, Bakker, Stephan J. L., Bartz, Traci M., Beilby, John, Bergman, Richard N., Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L., Bottinger, Erwin P., Braga, Daniele, Buckley, Brendan M., Buyske, Steve, Campbell, Harry, Chambers, John C., Collins, Francis S., Curran, Joanne E., De Borst, Gert J., De Craen, Anton J M, de Geus, Eco J. C., Dedoussis, George, Delgado, Graciela E., Den Ruijter, Hester M., Eiriksdottir, Gudny, Eriksson, Anna L., Esko, Toñu, Faul, Jessica D., Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas D., Heath, Andrew C., Hernandez, Dena G., Hindorff, Lucia A., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Hottenga, Jouke-Jan, Huang, Jie, Hung, Joseph, Hutri-Kähönen, Nina, Ingelsson, Erik, James, Alan L., Jansson, John Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E., Juonala, Markus, Kähönen, Mika, Karlsson, Magnus, Koistinen, Heikki A., Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Krämer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lee, Nanette R., Lind, Lars, Lindgren, Cecilia M., Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A. F., Männikkö, Reija, Marques-Vidal, Pedro, Martin, Nicholas G., McKenzie, Colin A., McKnight, Barbara, Mellström, Dan, Menni, Cristina, Montgomery, Grant W., Musk, Arthur W., Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Peyser, Patricia A., Pisinger, Charlotta, Porteous, David J., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rasmussen-Torvik, Laura J., Rawal, Rajesh, Rice, Treva K., Ridker, Paul M., Rose, Lynda M., Bien, Stephanie A., Rudan, Igor, Sanna, Serena, Sarzynski, Mark A., Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A., Sennblad, Bengt, Siemelink, Marten A., Silbernagel, Günther, Slagboom, P. Eline, Snieder, Harold, Staessen, Jan A., Stott, David J., Swertz, Morris A., Swift, Amy J., Taylor, Kent D., Tayo, Bamidele O., Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Völzke, Henry, Vonk, Judith M., Waeber, Ge'rard, Waldenberger, Melanie, Westendorp, Rudi G. J., Wild, Sarah H., Willemsen, Gonneke, Wolffenbuttel, Bruce H.R., Wong, Andrew, Wright, Alan F., Zhao, Wei, Zillikens, M. Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Böger, Carsten A, Boomsma, Dorret I., Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I., Ida Chen, Yii Der, Chines, Peter S., Cooper, Richard S., Cucca, Francesco, Cusi, Daniele, de Faire, Ulf, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans Jörgen, Gudnason, Vilmundur, Haiman, Christopher A., Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D., Jukema, J. Wouter, Kardia, Sharon L. R., Kivimaki, Mika, Kooner, Jaspal S., Kuh, Diana, Laakso, Markku, Lehtimäki, Terho, Le Marchand, Loic, März, Winfried, McCarthy, Mark I., Metspalu, Andres, Morris, Andrew P., Ohlsson, Claes, Palmer, Lyle J., Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M., Qi, Lu, Rauramaa, Rainer, Smith, Blair H., Sorensen, Thorkild I. A., Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J., Weir, David R., Whitfield, John B., Wilson, James F., Tyrrell, Jessica, Frayling, Timothy M., Barroso, Inês, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S., Hirschhorn, Joel N., Hunter, David J., Spector, Tim D., Strachan, David P., Van Duijn, Cornelia M., Heid, Iris M., Mohlke, Karen L., Marchini, Jonathan, Loos, Ruth J. F., Kilpeläinen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B., North, Kari E., Cupples, L. Adrienne, UMC Utrecht, Experimentele Afd. Cardiologie 1, Circulatory Health, In Vivo NMR ISI, Verpleegafd Vaatchirurgie D4 Oost, Onderzoek Vrouw Hart & Vaatziekten, Justice, Anne E., Winkler, Thomas W., Feitosa, Mary F., Graff, Misa, Fisher, Virginia A., Young, Kristin L, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S., Ahluwalia, Tarunveer S., Chu, Audrey Y, Heard-Costa, Nancy L., Lim, Elise, Perez, Jeremiah, Eicher, John D., Kutalik, Zolta'n, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph C., Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F., Bonnefond, Amelie, Bragg-Gresham, Jennifer L., Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Harder, Marie Neergaard, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E., Jackson, Anne U., Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E., Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Müller-Nurasyid, Martina, Navarro, Pau, Pe'russe, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A., Stanča'kova, Alena, Strawbridge, Rona J., Stringham, Heather M., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Van Der Laan, Sander W., van der Most, Peter J., Van Vliet-Ostaptchouk, Jana V., Vedantam, Sailaja L., Verweij, Niek, Vink, Jacqueline M., Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Zhao, Jing Hua, Zimmermann, Martina E., Zubair, Niha, Abecasis, Gonçalo R., Adair, Linda S., Afaq, Saima, Afzal, Uzma, Bakker, Stephan J. L., Bartz, Traci M., Beilby, John, Bergman, Richard N., Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L., Bottinger, Erwin P., Braga, Daniele, Buckley, Brendan M., Buyske, Steve, Campbell, Harry, Chambers, John C., Collins, Francis S., Curran, Joanne E., De Borst, Gert J., De Craen, Anton J M, de Geus, Eco J. C., Dedoussis, George, Delgado, Graciela E., Den Ruijter, Hester M., Eiriksdottir, Gudny, Eriksson, Anna L., Esko, Toñu, Faul, Jessica D., Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B., Hartman, Catharina A., Hassinen, Maija, Hastie, Nicholas D., Heath, Andrew C., Hernandez, Dena G., Hindorff, Lucia A., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Hottenga, Jouke-Jan, Huang, Jie, Hung, Joseph, Hutri-Kähönen, Nina, Ingelsson, Erik, James, Alan L., Jansson, John Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E., Juonala, Markus, Kähönen, Mika, Karlsson, Magnus, Koistinen, Heikki A., Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Krämer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A., Langenberg, Claudia, Launer, Lenore J., Leander, Karin, Lee, Nanette R., Lind, Lars, Lindgren, Cecilia M., Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A. F., Männikkö, Reija, Marques-Vidal, Pedro, Martin, Nicholas G., McKenzie, Colin A., McKnight, Barbara, Mellström, Dan, Menni, Cristina, Montgomery, Grant W., Musk, Arthur W., Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Peyser, Patricia A., Pisinger, Charlotta, Porteous, David J., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rasmussen-Torvik, Laura J., Rawal, Rajesh, Rice, Treva K., Ridker, Paul M., Rose, Lynda M., Bien, Stephanie A., Rudan, Igor, Sanna, Serena, Sarzynski, Mark A., Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A., Sennblad, Bengt, Siemelink, Marten A., Silbernagel, Günther, Slagboom, P. Eline, Snieder, Harold, Staessen, Jan A., Stott, David J., Swertz, Morris A., Swift, Amy J., Taylor, Kent D., Tayo, Bamidele O., Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Völzke, Henry, Vonk, Judith M., Waeber, Ge'rard, Waldenberger, Melanie, Westendorp, Rudi G. J., Wild, Sarah H., Willemsen, Gonneke, Wolffenbuttel, Bruce H.R., Wong, Andrew, Wright, Alan F., Zhao, Wei, Zillikens, M. Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Böger, Carsten A, Boomsma, Dorret I., Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I., Ida Chen, Yii Der, Chines, Peter S., Cooper, Richard S., Cucca, Francesco, Cusi, Daniele, de Faire, Ulf, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans Jörgen, Gudnason, Vilmundur, Haiman, Christopher A., Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D., Jukema, J. Wouter, Kardia, Sharon L. R., Kivimaki, Mika, Kooner, Jaspal S., Kuh, Diana, Laakso, Markku, Lehtimäki, Terho, Le Marchand, Loic, März, Winfried, McCarthy, Mark I., Metspalu, Andres, Morris, Andrew P., Ohlsson, Claes, Palmer, Lyle J., Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M., Qi, Lu, Rauramaa, Rainer, Smith, Blair H., Sorensen, Thorkild I. A., Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J., Weir, David R., Whitfield, John B., Wilson, James F., Tyrrell, Jessica, Frayling, Timothy M., Barroso, Inês, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S., Hirschhorn, Joel N., Hunter, David J., Spector, Tim D., Strachan, David P., Van Duijn, Cornelia M., Heid, Iris M., Mohlke, Karen L., Marchini, Jonathan, Loos, Ruth J. F., Kilpeläinen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B., North, Kari E., and Cupples, L. Adrienne

Published
2017

35. Multiethnic Exome-Wide Association Study of Subclinical AtherosclerosisCLINICAL PERSPECTIVE

Author

Boerwinkle, Eric, Vojinovic, Dina, Becker, Diane M., Van Setten, Jessica, Heckbert, Susan R., Bowden, Donald W., Oudkerk, Matthijs, Heiss, Gerardo, Yao, Jie, Deary, Ian J., Goodarzi, Mark O., Bis, Joshua C., Rotter, Jerome I., Fuster, Valentin, Išgum, Ivana, Guo, Xiuqing, Taylor, Kent D., Lyytikäinen, Leo-Pekka, Li-Gao, Ruifang, Rivadeneira, Fernando, Kavousi, Maryam, Sartori, Samantha, Dörr, Marcus, Smith, Albert V., Psaty, Bruce M., Kathiresan, Sekar, Völzke, Henry, Kral, Brian G., O'Donnell, Christopher J., Baber, Usman, Newman, Anne B., Rader, Daniel J., Peyser, Patricia A., Mehran, Roxana, Nguyen, Khanh-Dung, Tada, Hayato, Trompet, Stella, De Mutsert, Renée, Feitosa, Mary F., De Jong, Pim A., Natarajan, Pradeep, Mitchell, Braxton D., Yanek, Lisa R., Massaro, Joe, Vaidya, Dhananjay, Peloso, Gina M., Turner, Stephen T., Franco, Oscar H., Bielak, Lawrence F., Borecki, Ingrid B., Harris, Tamara B., Hoffmann, Udo, Raitakari, Olli T., Marioni, Riccardo E., Jukema, J. Wouter, Gudnason, Vilmundur, Mook-Kanamori, Dennis O., Teumer, Alexander, Cupples, L. Adrienne, Kardia, Sharon L.R., Amin, Najaf, Post, Wendy, Hwang, Shih-Jen, Chen, Yii-Der Ida, Pankow, James S., Mathias, Rasika, Rosendaal, Frits, Stitziel, Nathan O., North, Kari E., Wassel, Christina L., Wardlaw, Joanna M., Lehtimäki, Terho, Van Duijn, Cornelia M., Jhun, Min A, Yerges-Armstrong, Laura M., Isaacs, Aaron, Reilly, Dermot F., De Koning, Harry, Franceschini, Nora, Van Der Lugt, Aad, Becker, Lewis C., Felix, Stephan B., Raffield, Laura M., Dehghan, Abbas, Wojczynski, Mary K., Weiss, Stefan, Wilson, James G., Kähönen, Mika, Launer, Lenore J., Mosley, Thomas H., Demirkan, Ayse, O'Connell, Jeffrey R., De Vos, Bob D., Schminke, Ulf, Province, Michael A., Völker, Uwe, Carr, J. Jeffrey, Uitterlinden, Andre G., Cox, Amanda J., and Hofman, Albert

Subjects
cardiovascular diseases
Abstract

The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease (CHD). We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent CHD.

Published
2016
Full Text
View/download PDF

39. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

Justice, Anne E., primary, Winkler, Thomas W., additional, Feitosa, Mary F., additional, Graff, Misa, additional, Fisher, Virginia A., additional, Young, Kristin, additional, Barata, Llilda, additional, Deng, Xuan, additional, Czajkowski, Jacek, additional, Hadley, David, additional, Ngwa, Julius S., additional, Ahluwalia, Tarunveer S., additional, Chu, Audrey Y., additional, Heard-Costa, Nancy L., additional, Lim, Elise, additional, Perez, Jeremiah, additional, Eicher, John D., additional, Kutalik, Zoltán, additional, Xue, Luting, additional, Mahajan, Anubha, additional, Renström, Frida, additional, Wu, Joseph, additional, Qi, Qibin, additional, Ahmad, Shafqat, additional, Alfred, Tamuno, additional, Amin, Najaf, additional, Bielak, Lawrence F., additional, Bonnefond, Amelie, additional, Bragg, Jennifer, additional, Cadby, Gemma, additional, Chittani, Martina, additional, Coggeshall, Scott, additional, Corre, Tanguy, additional, Direk, Nese, additional, Eriksson, Joel, additional, Fischer, Krista, additional, Gorski, Mathias, additional, Neergaard Harder, Marie, additional, Horikoshi, Momoko, additional, Huang, Tao, additional, Huffman, Jennifer E., additional, Jackson, Anne U., additional, Justesen, Johanne Marie, additional, Kanoni, Stavroula, additional, Kinnunen, Leena, additional, Kleber, Marcus E., additional, Komulainen, Pirjo, additional, Kumari, Meena, additional, Lim, Unhee, additional, Luan, Jian'an, additional, Lyytikäinen, Leo-Pekka, additional, Mangino, Massimo, additional, Manichaikul, Ani, additional, Marten, Jonathan, additional, Middelberg, Rita P. S., additional, Müller-Nurasyid, Martina, additional, Navarro, Pau, additional, Pérusse, Louis, additional, Pervjakova, Natalia, additional, Sarti, Cinzia, additional, Smith, Albert Vernon, additional, Smith, Jennifer A., additional, Stančáková, Alena, additional, Strawbridge, Rona J., additional, Stringham, Heather M., additional, Sung, Yun Ju, additional, Tanaka, Toshiko, additional, Teumer, Alexander, additional, Trompet, Stella, additional, van der Laan, Sander W., additional, van der Most, Peter J., additional, Van Vliet-Ostaptchouk, Jana V., additional, Vedantam, Sailaja L., additional, Verweij, Niek, additional, Vink, Jacqueline M., additional, Vitart, Veronique, additional, Wu, Ying, additional, Yengo, Loic, additional, Zhang, Weihua, additional, Hua Zhao, Jing, additional, Zimmermann, Martina E., additional, Zubair, Niha, additional, Abecasis, Gonçalo R., additional, Adair, Linda S., additional, Afaq, Saima, additional, Afzal, Uzma, additional, Bakker, Stephan J. L., additional, Bartz, Traci M., additional, Beilby, John, additional, Bergman, Richard N., additional, Bergmann, Sven, additional, Biffar, Reiner, additional, Blangero, John, additional, Boerwinkle, Eric, additional, Bonnycastle, Lori L., additional, Bottinger, Erwin, additional, Braga, Daniele, additional, Buckley, Brendan M., additional, Buyske, Steve, additional, Campbell, Harry, additional, Chambers, John C., additional, Collins, Francis S., additional, Curran, Joanne E., additional, de Borst, Gert J., additional, de Craen, Anton J. M., additional, de Geus, Eco J. C., additional, Dedoussis, George, additional, Delgado, Graciela E., additional, den Ruijter, Hester M., additional, Eiriksdottir, Gudny, additional, Eriksson, Anna L., additional, Esko, Tõnu, additional, Faul, Jessica D., additional, Ford, Ian, additional, Forrester, Terrence, additional, Gertow, Karl, additional, Gigante, Bruna, additional, Glorioso, Nicola, additional, Gong, Jian, additional, Grallert, Harald, additional, Grammer, Tanja B., additional, Grarup, Niels, additional, Haitjema, Saskia, additional, Hallmans, Göran, additional, Hamsten, Anders, additional, Hansen, Torben, additional, Harris, Tamara B., additional, Hartman, Catharina A., additional, Hassinen, Maija, additional, Hastie, Nicholas D., additional, Heath, Andrew C., additional, Hernandez, Dena, additional, Hindorff, Lucia, additional, Hocking, Lynne J., additional, Hollensted, Mette, additional, Holmen, Oddgeir L., additional, Homuth, Georg, additional, Jan Hottenga, Jouke, additional, Huang, Jie, additional, Hung, Joseph, additional, Hutri-Kähönen, Nina, additional, Ingelsson, Erik, additional, James, Alan L., additional, Jansson, John-Olov, additional, Jarvelin, Marjo-Riitta, additional, Jhun, Min A., additional, Jørgensen, Marit E., additional, Juonala, Markus, additional, Kähönen, Mika, additional, Karlsson, Magnus, additional, Koistinen, Heikki A., additional, Kolcic, Ivana, additional, Kolovou, Genovefa, additional, Kooperberg, Charles, additional, Krämer, Bernhard K., additional, Kuusisto, Johanna, additional, Kvaløy, Kirsti, additional, Lakka, Timo A., additional, Langenberg, Claudia, additional, Launer, Lenore J., additional, Leander, Karin, additional, Lee, Nanette R., additional, Lind, Lars, additional, Lindgren, Cecilia M., additional, Linneberg, Allan, additional, Lobbens, Stephane, additional, Loh, Marie, additional, Lorentzon, Mattias, additional, Luben, Robert, additional, Lubke, Gitta, additional, Ludolph-Donislawski, Anja, additional, Lupoli, Sara, additional, Madden, Pamela A. F., additional, Männikkö, Reija, additional, Marques-Vidal, Pedro, additional, Martin, Nicholas G., additional, McKenzie, Colin A., additional, McKnight, Barbara, additional, Mellström, Dan, additional, Menni, Cristina, additional, Montgomery, Grant W., additional, Musk, AW, additional, Narisu, Narisu, additional, Nauck, Matthias, additional, Nolte, Ilja M., additional, Oldehinkel, Albertine J., additional, Olden, Matthias, additional, Ong, Ken K., additional, Padmanabhan, Sandosh, additional, Peyser, Patricia A., additional, Pisinger, Charlotta, additional, Porteous, David J., additional, Raitakari, Olli T., additional, Rankinen, Tuomo, additional, Rao, D. C., additional, Rasmussen-Torvik, Laura J., additional, Rawal, Rajesh, additional, Rice, Treva, additional, Ridker, Paul M., additional, Rose, Lynda M., additional, Bien, Stephanie A., additional, Rudan, Igor, additional, Sanna, Serena, additional, Sarzynski, Mark A., additional, Sattar, Naveed, additional, Savonen, Kai, additional, Schlessinger, David, additional, Scholtens, Salome, additional, Schurmann, Claudia, additional, Scott, Robert A., additional, Sennblad, Bengt, additional, Siemelink, Marten A., additional, Silbernagel, Günther, additional, Slagboom, P Eline, additional, Snieder, Harold, additional, Staessen, Jan A., additional, Stott, David J., additional, Swertz, Morris A., additional, Swift, Amy J., additional, Taylor, Kent D., additional, Tayo, Bamidele O., additional, Thorand, Barbara, additional, Thuillier, Dorothee, additional, Tuomilehto, Jaakko, additional, Uitterlinden, Andre G., additional, Vandenput, Liesbeth, additional, Vohl, Marie-Claude, additional, Völzke, Henry, additional, Vonk, Judith M., additional, Waeber, Gérard, additional, Waldenberger, Melanie, additional, Westendorp, R. G. J., additional, Wild, Sarah, additional, Willemsen, Gonneke, additional, Wolffenbuttel, Bruce H. R., additional, Wong, Andrew, additional, Wright, Alan F., additional, Zhao, Wei, additional, Zillikens, M Carola, additional, Baldassarre, Damiano, additional, Balkau, Beverley, additional, Bandinelli, Stefania, additional, Böger, Carsten A., additional, Boomsma, Dorret I., additional, Bouchard, Claude, additional, Bruinenberg, Marcel, additional, Chasman, Daniel I., additional, Chen, Yii-DerIda, additional, Chines, Peter S., additional, Cooper, Richard S., additional, Cucca, Francesco, additional, Cusi, Daniele, additional, Faire, Ulf de, additional, Ferrucci, Luigi, additional, Franks, Paul W., additional, Froguel, Philippe, additional, Gordon-Larsen, Penny, additional, Grabe, Hans- Jörgen, additional, Gudnason, Vilmundur, additional, Haiman, Christopher A., additional, Hayward, Caroline, additional, Hveem, Kristian, additional, Johnson, Andrew D., additional, Wouter Jukema, J, additional, Kardia, Sharon L. R., additional, Kivimaki, Mika, additional, Kooner, Jaspal S., additional, Kuh, Diana, additional, Laakso, Markku, additional, Lehtimäki, Terho, additional, Marchand, Loic Le, additional, März, Winfried, additional, McCarthy, Mark I., additional, Metspalu, Andres, additional, Morris, Andrew P., additional, Ohlsson, Claes, additional, Palmer, Lyle J., additional, Pasterkamp, Gerard, additional, Pedersen, Oluf, additional, Peters, Annette, additional, Peters, Ulrike, additional, Polasek, Ozren, additional, Psaty, Bruce M., additional, Qi, Lu, additional, Rauramaa, Rainer, additional, Smith, Blair H., additional, Sørensen, Thorkild I. A., additional, Strauch, Konstantin, additional, Tiemeier, Henning, additional, Tremoli, Elena, additional, van der Harst, Pim, additional, Vestergaard, Henrik, additional, Vollenweider, Peter, additional, Wareham, Nicholas J., additional, Weir, David R., additional, Whitfield, John B., additional, Wilson, James F., additional, Tyrrell, Jessica, additional, Frayling, Timothy M., additional, Barroso, Inês, additional, Boehnke, Michael, additional, Deloukas, Panagiotis, additional, Fox, Caroline S., additional, Hirschhorn, Joel N., additional, Hunter, David J., additional, Spector, Tim D., additional, Strachan, David P., additional, van Duijn, Cornelia M., additional, Heid, Iris M., additional, Mohlke, Karen L., additional, Marchini, Jonathan, additional, Loos, Ruth J. F., additional, Kilpeläinen, Tuomas O., additional, Liu, Ching-Ti, additional, Borecki, Ingrid B., additional, North, Kari E., additional, and Cupples, L Adrienne, additional

Published
2017
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40. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

Author

Natarajan, Pradeep, primary, Bis, Joshua C., additional, Bielak, Lawrence F., additional, Cox, Amanda J., additional, Dörr, Marcus, additional, Feitosa, Mary F., additional, Franceschini, Nora, additional, Guo, Xiuqing, additional, Hwang, Shih-Jen, additional, Isaacs, Aaron, additional, Jhun, Min A, additional, Kavousi, Maryam, additional, Li-Gao, Ruifang, additional, Lyytikäinen, Leo-Pekka, additional, Marioni, Riccardo E., additional, Schminke, Ulf, additional, Stitziel, Nathan O., additional, Tada, Hayato, additional, van Setten, Jessica, additional, Smith, Albert V., additional, Vojinovic, Dina, additional, Yanek, Lisa R., additional, Yao, Jie, additional, Yerges-Armstrong, Laura M., additional, Amin, Najaf, additional, Baber, Usman, additional, Borecki, Ingrid B., additional, Carr, J. Jeffrey, additional, Chen, Yii-Der Ida, additional, Cupples, L. Adrienne, additional, de Jong, Pim A., additional, de Koning, Harry, additional, de Vos, Bob D., additional, Demirkan, Ayse, additional, Fuster, Valentin, additional, Franco, Oscar H., additional, Goodarzi, Mark O., additional, Harris, Tamara B., additional, Heckbert, Susan R., additional, Heiss, Gerardo, additional, Hoffmann, Udo, additional, Hofman, Albert, additional, Išgum, Ivana, additional, Jukema, J. Wouter, additional, Kähönen, Mika, additional, Kardia, Sharon L.R., additional, Kral, Brian G., additional, Launer, Lenore J., additional, Massaro, Joe, additional, Mehran, Roxana, additional, Mitchell, Braxton D., additional, Mosley, Thomas H., additional, de Mutsert, Renée, additional, Newman, Anne B., additional, Nguyen, Khanh-dung, additional, North, Kari E., additional, O’Connell, Jeffrey R., additional, Oudkerk, Matthijs, additional, Pankow, James S., additional, Peloso, Gina M., additional, Post, Wendy, additional, Province, Michael A., additional, Raffield, Laura M., additional, Raitakari, Olli T., additional, Reilly, Dermot F., additional, Rivadeneira, Fernando, additional, Rosendaal, Frits, additional, Sartori, Samantha, additional, Taylor, Kent D., additional, Teumer, Alexander, additional, Trompet, Stella, additional, Turner, Stephen T., additional, Uitterlinden, Andre G., additional, Vaidya, Dhananjay, additional, van der Lugt, Aad, additional, Völker, Uwe, additional, Wardlaw, Joanna M., additional, Wassel, Christina L., additional, Weiss, Stefan, additional, Wojczynski, Mary K., additional, Becker, Diane M., additional, Becker, Lewis C., additional, Boerwinkle, Eric, additional, Bowden, Donald W., additional, Deary, Ian J., additional, Dehghan, Abbas, additional, Felix, Stephan B., additional, Gudnason, Vilmundur, additional, Lehtimäki, Terho, additional, Mathias, Rasika, additional, Mook-Kanamori, Dennis O., additional, Psaty, Bruce M., additional, Rader, Daniel J., additional, Rotter, Jerome I., additional, Wilson, James G., additional, van Duijn, Cornelia M., additional, Völzke, Henry, additional, Kathiresan, Sekar, additional, Peyser, Patricia A., additional, and O’Donnell, Christopher J., additional

Published
2016
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41. The association between lower educational attainment and depression owing to shared genetic effects? Results in ∼25 000 subjects: Results in ~25,000 subjects

Author

Peyrot, W. J., Lee, S. H., Milaneschi, Y., Abdellaoui, A., Byrne, E. M., Esko, T., de Geus, E. J. C., Hemani, G., Hottenga, J. J., Kloiber, S., Levinson, D. F., Lucae, S., Martin, N. G., Medland, S. E., Metspalu, A., Milani, L., Noethen, M. M., Potash, J. B., Rietschel, M., Rietveld, C. A., Ripke, S., Shi, J., Willemsen, G., Zhu, Z., Boomsma, D. I., Wray, N. R., Penninx, B. W. J. H., Lewis, C. M., Hamilton, S. P., Weissman, M. M., Breen, G., Blackwood, D. H., Cichon, S., Heath, A. C., Holsboer, F., Madden, Pamela A., McGuffin, P., Muglia, P., Pergadia, M. L., Lin, D., Müller-Myhsok, B., Steinberg, S., Grabe, H. J., Lichtenstein, P., Magnusson, P., Perlis, R. H., Preisig, M., Smoller, J. W., Stefansson, K., Uher, R., Kutalik, Z., Tansey, K. E., Teumer, A., Viktorin, A., Barnes, M. R., Bettecken, T., Binder, E. B., Breuer, R., Castro, V. M., Churchill, S. E., Coryell, W. H., Craddock, N., Craig, I. W., Czamara, D., Degenhardt, F., Farmer, A. E., Fava, M., Frank, J., Gainer, V. S., Gallagher, P. J., Gordon, S. D., Goryachev, S., Gross, M., Guipponi, M., Henders, A. K., Herms, S., Hickie, I. B., Hoefels, S., Hoogendijk, W., Iosifescu, D. V., Ising, M., Jones, I., Jones, L., Jung-Ying, T., Knowles, J. A., Kohane, I. S., Kohli, M. A., Korszun, A., Landen, M., Lawson, W. B., Lewis, G., Macintyre, D., Maier, W., Mattheisen, M., McGrath, P. J., McIntosh, A., McLean, A., Middeldorp, C. M., Middleton, L., Montgomery, G. M., Murphy, S. N., Nauck, M., Nolen, W. A., Nyholt, Dale R., O'Donovan, M., Oskarsson, H., Pedersen, N., Scheftner, W. A., Schulz, A., Schulze, T. G., Shyn, S. I., Sigurdsson, E., Slager, S. L., Smit, J. H., Stefansson, H., Steffens, M., Thorgeirsson, T., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E. J., van Grootheest, G., Völzke, H., Weilburg, J. B., Zitman, F. G., Neale, B., Daly, M., Sullivan, P. F., Agrawal, Arpana, Albrecht, Eva, Z Alizadeh, Behrooz, Allik, J. ri, Amin, Najaf, Attia, John R., Bandinelli, Stefania, Barnard, John, Bastardot, Franois, e Baumeister, Sebastian, Beauchamp, Jonathan, Benjamin, Daniel J., Benke, Kelly S., Bennett, David A., Berger, Klaus, Bielak, Lawrence F., Bierut, Laura J., Boatman, Jeffrey A., Boyle, Patricia A., Bültmann, Ute, Campbell, Harry, Cesarini, David, Chabris, Christopher F., Cherkas, Lynn, Chung, Mina K., Conley, Dalton, Cucca, Francesco, Davey-Smith, George, Davies, Gail, de Andrade, Mariza, de Jager, Philip L., de Leeuw, Christiaan, de Neve, Jan-Emmanuel, Deary, Ian J., Dedoussis, George V., Deloukas, Panos, Derringer, Jaime, Dimitriou, Maria, Eiriksdottir, Gudny, Eklund, Niina, Elderson, Martin F., Eriksson, Johan G., Evans, Daniel S., Evans, David M., Faul, Jessica D., Fehrmann, Rudolf, Ferrucci, Luigi, Fischer, Krista, Franke, Lude, Garcia, Melissa E., Gieger, Christian, Gjessing, Hkon K., Groenen, Patrick J. F., Grönberg, Henrik, Gudnason, Vilmundur, Hägg, Sara, Hall, Per, Harris, Jennifer R., Harris, Juliette M., Harris, Tamara B., Hastie, Nicholas D., Hayward, Caroline, Hernandez, Dena G., Hoffmann, Wolgang, Hofman, Adriaan, Hofman, Albert, Holle, Rolf, Holliday, Elizabeth G., Holzapfel, Christina, Iacono, William G., Ibrahim-Verbaas, Carla A., Illig, Thomas, Ingelsson, Erik, Jacobsson, Bo, Järvelin, Marjo-Riitta, Jhun, Min A., Johannesson, Magnus, Joshi, Peter K., Jugessur, Astanand, Kaakinen, Marika, Kähönen, Mika, Kanoni, Stavroula, Kaprio, Jaakkko, Kardia, Sharon L. R., Karjalainen, Juha, Kirkpatrick, Robert M., Koellinger, Philipp D., Kolcic, Ivana, Kowgier, Matthew, Kristiansson, Kati, Krueger, Robert F., Kutalik, Z. ltan, Lahti, Jari, Laibson, David, Latvala, Antti, Launer, Lenore J., Lawlor, Debbie A., Lethimäki, Terho, Li, Jingmei, Lichtenstein, Paul, Lichtner, Peter K., Liewald, David C., Lin, Peng, Lind, Penelope A., Liu, Yongmei, Lohman, Kurt, Loitfelder, Marisa, Magnusson, Patrick K. E., Mäkinen, Tomi E., Vidal, Pedro Marques, Martin, Nicolas W., Masala, Marco, McGue, Matt, McMahon, George, Meirelles, Osorio, Meyer, Michelle N., Mielck, Andreas, Miller, Michael B., Montgomery, Grant W., Mukherjee, Sutapa, Myhre, Ronny, Nuotio, Marja-Liisa, J Oldmeadow, Christopher, Oostra, Ben A., Palmer, Lyle J., Palotie, Aarno, Perola, Markus, Petrovic, Katja E., Peyser, Patricia A., Polašek, Ozren, Posthuma, Danielle, Preisig, Martin, Quaye, Lydia, Räikkönen, Katri, Raitakari, Olli T., Realo, Anu, Reinmaa, Eva, Rice, John P., Ring, Susan M., Ripatti, Samuli, Rivadeneira, Fernando, Rizzi, Thais S., Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sarin, Antti-Pekka, Schlessinger, David, Schmidt, Helena, Schmidt, Reinhold, Scott, Rodney J., Shakhbazov, Konstantin, Smith, Albert V., Smith, Jennifer A., Snieder, Harold, St Pourcain, Beate, Starr, John M., Sul, Jae Hoon, Surakka, Ida, Svento, Rauli, Tanaka, Toshiko, Terracciano, Antonio, Teumer, Alexander, Thurik, A. Roy, Tiemeier, Henning, Timpson, Nicholas J., Uitterlinden, André G., van der Loos, Matthijs J. H. M., van Duijn, Cornelia M., van Rooij, Frank J. A., van Wagoner, David R., Vartiainen, Erkki, Viikari, Jorma, Visscher, Peter M., Vitart, Veronique, Vollenweider, Peter K., Völzke, Henry, Vonk, Judith M., Waeber, G. rard, Weir, David R., Wellmann, J. rgen, Westra, Harm-Jan, Wichmann, H. Erich, Widen, Elisabeth, Wilson, James F., Wright, Alan F., Yang, Jian, Yu, Lei, Zhao, Wei, and Academic Medical Center

Subjects
Adult, Male, Psychiatric Status Rating Scales, Likelihood Functions, Genotype, Estonia/epidemiology, Netherlands/epidemiology, Depressive Disorder, Major/epidemiology, Middle Aged, Polymorphism, Single Nucleotide/genetics, Cohort Studies, Odds Ratio, Educational Status, Humans, Regression Analysis, Female, Gene-Environment Interaction, Genetic Association Studies, Aged
Abstract

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ∼120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

Published
2015

42. Whole Genome Sequencing Identifies CRISPLD2as a Lung Function Gene in Children With Asthma

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L., Ahluwalia, Tarunveer S., Cho, Michael H., Qiao, Dandi, Kelly, Rachel S., Chu, Su H., Virkud, Yamini V., Huang, Mengna, Barnes, Kathleen C., Burchard, Esteban G., Eng, Celeste, Hu, Donglei, Celedón, Juan C., Daya, Michelle, Levin, Albert M., Gui, Hongsheng, Williams, L. Keoki, Forno, Erick, Mak, Angel C.Y., Avila, Lydiana, Soto-Quiros, Manuel E., Cloutier, Michelle M., Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A., Lange, Christoph, Weiss, Scott T., Lasky-Su, Jessica A., Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Palmer Allred, Nicholette (Nichole), Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Cho, Michael H., Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Holly, Kramer, Hong, Elliott, Hoth, Karin, (Agnes) Hsiung, Chao, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A., Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kachroo, Priyadarshini, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun Shawn, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lubitz, Steven, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah A., Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton, Montasser, May E., Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Su-Lasky, Jessica, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Wang, Fei Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zekavat, Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, and Zoellner, Sebastian

Abstract

Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.

Published
2019
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43. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

Author

Gallego-Fabrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullell, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martin-Campos, Jesús M., Sobrino, Tomás, Castillo, José, Millán, Mònica, Muñoz-Narbona, Lucía, López-Cancio, Elena, Ribó, Marc, Alvarez-Sabin, Jose, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan F., Segura, Tomas, Serrano-Heras, Gemma, Marti-Fabregas, Joan, Freijo-Guerrero, Marimar, Moniche, Francisco, Castellanos, Maria del Mar, Morrison, Alanna C., Smith, Nicholas L., de Vries, Paul S., Fernández-Cadenas, Israel, Sabater-Lleal, Maria, Dehghan, Abbas, Heath, Adam S., Morrison, Alanna C., Reiner, Alex P., Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M., Hayward, Caroline, Ward-Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P., Tregouet, David A., Mook-Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W., Leebeek, Frank W.G., Rosendaal, Frits R., Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A., Bressler, Jan, Huffman, Jennifer E., Rotter, Jerome I., Yao, Jie, Wilson, James F., Bis, Joshua C., Hahn, Julie M., Desch, Karl C., Wiggins, Kerri L., Díez-Ahijado, Laia, Raffield, Laura M., Bielak, Lawrence F., Yanek, Lisa R., Kleber, Marcus E., Sabater-Lleal, Maria, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Conomos, Matthew P., Liu, Melissa, Brown, Michael R., Jhun, Min-A, Chen, Ming-Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L., Peyser, Patricia A., Elliot, Paul, de Vries, Paul S., Wei, Peng, Wild, Philipp S., Morange, Pierre E., van der Harst, Pim, Yang, Qiong, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M., Cox, Simon R., Trompet, Stella, Felix, Stephan B., Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, and Guo, Xiuqing

Abstract

Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient’s prognosis.

Published
2024
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44. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

Author

Experimentele Afd. Cardiologie 1, Researchgr. Systems Radiology, Circulatory Health, Beeldverwerking ISI, Brain, Natarajan, Pradeep, Bis, Joshua C, Bielak, Lawrence F, Cox, Amanda J, Dörr, Marcus, Feitosa, Mary F, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, Isaacs, Aaron, Jhun, Min A, Kavousi, Maryam, Li-Gao, Ruifang, Lyytikäinen, Leo-Pekka, Marioni, Riccardo E, Schminke, Ulf, Stitziel, Nathan O, Tada, Hayato, van Setten, Jessica, Smith, Albert V, Vojinovic, Dina, Yanek, Lisa R, Yao, Jie, Yerges-Armstrong, Laura M, Amin, Najaf, Baber, Usman, Borecki, Ingrid B, Carr, J Jeffrey, Chen, Yii-Der Ida, Cupples, L Adrienne, de Jong, Pim A, de Koning, Harry, de Vos, Bob D, Demirkan, Ayse, Fuster, Valentin, Franco, Oscar H, Goodarzi, Mark O, Harris, Tamara B, Heckbert, Susan R, Heiss, Gerardo, Hoffmann, Udo, Hofman, Albert, Išgum, Ivana, Jukema, J Wouter, Kähönen, Mika, Kardia, Sharon L R, Kral, Brian G, Launer, Lenore J, Massaro, Joseph, Mehran, Roxana, CHARGE Consortium, Experimentele Afd. Cardiologie 1, Researchgr. Systems Radiology, Circulatory Health, Beeldverwerking ISI, Brain, Natarajan, Pradeep, Bis, Joshua C, Bielak, Lawrence F, Cox, Amanda J, Dörr, Marcus, Feitosa, Mary F, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, Isaacs, Aaron, Jhun, Min A, Kavousi, Maryam, Li-Gao, Ruifang, Lyytikäinen, Leo-Pekka, Marioni, Riccardo E, Schminke, Ulf, Stitziel, Nathan O, Tada, Hayato, van Setten, Jessica, Smith, Albert V, Vojinovic, Dina, Yanek, Lisa R, Yao, Jie, Yerges-Armstrong, Laura M, Amin, Najaf, Baber, Usman, Borecki, Ingrid B, Carr, J Jeffrey, Chen, Yii-Der Ida, Cupples, L Adrienne, de Jong, Pim A, de Koning, Harry, de Vos, Bob D, Demirkan, Ayse, Fuster, Valentin, Franco, Oscar H, Goodarzi, Mark O, Harris, Tamara B, Heckbert, Susan R, Heiss, Gerardo, Hoffmann, Udo, Hofman, Albert, Išgum, Ivana, Jukema, J Wouter, Kähönen, Mika, Kardia, Sharon L R, Kral, Brian G, Launer, Lenore J, Massaro, Joseph, Mehran, Roxana, and CHARGE Consortium

Published
2016

45. SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function

Author

Li, Man, Li, Yong, Weeks, Olivia, Mijatovic, Vladan, Teumer, Alexander, Huffman, Jennifer E, Tromp, Gerard, Fuchsberger, Christian, Gorski, Mathia, Lyytikäinen, Leo Pekka, Nutile, Teresa, Sedaghat, Sanaz, Sorice, Rossella, Tin, Adrienne, Yang, Qiong, Ahluwalia, Tarunveer S, Arking, Dan E, Bihlmeyer, Nathan A, Böger, Carsten A, Carroll, Robert J, Chasman, Daniel I, Cornelis, Marilyn C, Dehghan, Abba, Faul, Jessica D, Feitosa, Mary F, Gambaro, Giovanni, Gasparini, Paolo, Giulianini, Franco, Heid, Iri, Huang, Jinyan, Imboden, Medea, Jackson, Anne U, Jeff, Janina, Jhun, Min A, Katz, Ronit, Kifley, Annette, Kilpeläinen, Tuomas O, Kumar, Ashish, Laakso, Markku, Li Gao, Ruifang, Lohman, Kurt, Lu, Yingchang, Mägi, Reedik, Malerba, Giovanni, Mihailov, Evelin, Mohlke, Karen L, Mook Kanamori, Dennis O, Robino, Antonietta, Ruderfer, Dougla, Salvi, Erika, Schick, Ursula M, Schulz, Christina Alexandra, Smith, Albert V, Smith, Jennifer A, Traglia, Michela, Yerges Armstrong, Laura M, Zhao, Wei, Goodarzi, Mark O, Kraja, Aldi T, Liu, Chunyu, Wessel, Jennifer, Boerwinkle, Eric, Borecki, Ingrid B, Bork Jensen, Jette, Bottinger, Erwin P, Braga, Daniele, Brandslund, Ivan, Brody, Jennifer A, Campbell, Archie, Carey, David J, Christensen, Cramer, Coresh, Josef, Crook, Errol, Curhan, Gary C, Cusi, Daniele, de Boer, Ian H, de Vries, Aiko P. J, Denny, Joshua C, Devuyst, Olivier, Dreisbach, Albert W, Endlich, Karlhan, Esko, Tõnu, Franco, Oscar H, Fulop, Tibor, Gerhard, Glenn S, Glümer, Charlotte, Gottesman, Omri, Grarup, Niel, Gudnason, Vilmundur, Harris, Tamara B, Hayward, Caroline, Hocking, Lynne, Hofman, Albert, Hu, Frank B, Husemoen, Lise Lotte N, Jackson, Rebecca D, Jørgensen, Torben, Jørgensen, Marit E, Kähönen, Mika, Kardia, Sharon L. R, König, Wolfgang, Kooperberg, Charle, Kriebel, Jennifer, Launer, Lenore J, Lauritzen, Torsten, Lehtimäki, Terho, Levy, Daniel, Linksted, Pamela, Linneberg, Allan, Liu, Yongmei, Loos, Ruth J. F, Lupo, Antonio, Meisinger, Christine, Melander, Olle, Metspalu, Andre, Mitchell, Paul, Nauck, Matthia, Nürnberg, Peter, Orho Melander, Marju, Parsa, Afshin, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Porteous, David, Probst Hensch, Nicole M, Psaty, Bruce M, Qi, Lu, Raitakari, Olli T, Reiner, Alex P, Rettig, Rainer, Ridker, Paul M, Rivadeneira, Fernando, Rossouw, Jacques E, Schmidt, Frank, Siscovick, David, Soranzo, Nicole, Strauch, Konstantin, Toniolo, Daniela, Turner, Stephen T, Uitterlinden, André G, Ulivi, Sheila, Velayutham, Dinesh, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wang, Jie Jin, Weir, David R, Witte, Daniel, Kuivaniemi, Helena, Fox, Caroline S, Franceschini, Nora, Goessling, Wolfram, Köttgen, Anna, Chu, Audrey Y., Gambaro, Giovanni (ORCID:0000-0001-5733-2370), Li, Man, Li, Yong, Weeks, Olivia, Mijatovic, Vladan, Teumer, Alexander, Huffman, Jennifer E, Tromp, Gerard, Fuchsberger, Christian, Gorski, Mathia, Lyytikäinen, Leo Pekka, Nutile, Teresa, Sedaghat, Sanaz, Sorice, Rossella, Tin, Adrienne, Yang, Qiong, Ahluwalia, Tarunveer S, Arking, Dan E, Bihlmeyer, Nathan A, Böger, Carsten A, Carroll, Robert J, Chasman, Daniel I, Cornelis, Marilyn C, Dehghan, Abba, Faul, Jessica D, Feitosa, Mary F, Gambaro, Giovanni, Gasparini, Paolo, Giulianini, Franco, Heid, Iri, Huang, Jinyan, Imboden, Medea, Jackson, Anne U, Jeff, Janina, Jhun, Min A, Katz, Ronit, Kifley, Annette, Kilpeläinen, Tuomas O, Kumar, Ashish, Laakso, Markku, Li Gao, Ruifang, Lohman, Kurt, Lu, Yingchang, Mägi, Reedik, Malerba, Giovanni, Mihailov, Evelin, Mohlke, Karen L, Mook Kanamori, Dennis O, Robino, Antonietta, Ruderfer, Dougla, Salvi, Erika, Schick, Ursula M, Schulz, Christina Alexandra, Smith, Albert V, Smith, Jennifer A, Traglia, Michela, Yerges Armstrong, Laura M, Zhao, Wei, Goodarzi, Mark O, Kraja, Aldi T, Liu, Chunyu, Wessel, Jennifer, Boerwinkle, Eric, Borecki, Ingrid B, Bork Jensen, Jette, Bottinger, Erwin P, Braga, Daniele, Brandslund, Ivan, Brody, Jennifer A, Campbell, Archie, Carey, David J, Christensen, Cramer, Coresh, Josef, Crook, Errol, Curhan, Gary C, Cusi, Daniele, de Boer, Ian H, de Vries, Aiko P. J, Denny, Joshua C, Devuyst, Olivier, Dreisbach, Albert W, Endlich, Karlhan, Esko, Tõnu, Franco, Oscar H, Fulop, Tibor, Gerhard, Glenn S, Glümer, Charlotte, Gottesman, Omri, Grarup, Niel, Gudnason, Vilmundur, Harris, Tamara B, Hayward, Caroline, Hocking, Lynne, Hofman, Albert, Hu, Frank B, Husemoen, Lise Lotte N, Jackson, Rebecca D, Jørgensen, Torben, Jørgensen, Marit E, Kähönen, Mika, Kardia, Sharon L. R, König, Wolfgang, Kooperberg, Charle, Kriebel, Jennifer, Launer, Lenore J, Lauritzen, Torsten, Lehtimäki, Terho, Levy, Daniel, Linksted, Pamela, Linneberg, Allan, Liu, Yongmei, Loos, Ruth J. F, Lupo, Antonio, Meisinger, Christine, Melander, Olle, Metspalu, Andre, Mitchell, Paul, Nauck, Matthia, Nürnberg, Peter, Orho Melander, Marju, Parsa, Afshin, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Porteous, David, Probst Hensch, Nicole M, Psaty, Bruce M, Qi, Lu, Raitakari, Olli T, Reiner, Alex P, Rettig, Rainer, Ridker, Paul M, Rivadeneira, Fernando, Rossouw, Jacques E, Schmidt, Frank, Siscovick, David, Soranzo, Nicole, Strauch, Konstantin, Toniolo, Daniela, Turner, Stephen T, Uitterlinden, André G, Ulivi, Sheila, Velayutham, Dinesh, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wang, Jie Jin, Weir, David R, Witte, Daniel, Kuivaniemi, Helena, Fox, Caroline S, Franceschini, Nora, Goessling, Wolfram, Köttgen, Anna, Chu, Audrey Y., and Gambaro, Giovanni (ORCID:0000-0001-5733-2370)

Abstract

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3.7×10-7), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10-8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

Published
2016

46. A Statistical Approach for Testing Cross-Phenotype Effects of Rare Variants

Author

Broadaway, K. Alaine, primary, Cutler, David J., additional, Duncan, Richard, additional, Moore, Jacob L., additional, Ware, Erin B., additional, Jhun, Min A., additional, Bielak, Lawrence F., additional, Zhao, Wei, additional, Smith, Jennifer A., additional, Peyser, Patricia A., additional, Kardia, Sharon L.R., additional, Ghosh, Debashis, additional, and Epstein, Michael P., additional

Published
2016
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47. Abstract 32: Novel Genetic Loci for Blood Pressure Regulation Identified by the Analysis of DNA Methylation

Author

Richard, Melissa A, primary, Huan, Tianxiao, additional, Ligthart, Symen, additional, Dehghan, Abbas, additional, Marioni, Riccardo E, additional, Brody, Jennifer A, additional, Sotoodehnia, Nona, additional, Jhun, Min A, additional, Kardia, Sharon L, additional, Smith, Jennifer A, additional, Irvin, M R, additional, Arnett, Donna K, additional, Aslibekyan, Stella, additional, Shen, J C, additional, Baccarelli, Andrea, additional, Just, Allan C, additional, Tsai, Pei-Chien, additional, Bell, Jordana T, additional, Spector, Tim D, additional, Guo, Xiuqing, additional, Rotter, Jerome A, additional, Palmas, Walter, additional, Liu, Yongmei, additional, Levy, Daniel, additional, and Fornage, Myriam, additional

Published
2016
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48. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

Author

de Vries, Paul S., Chasman, Daniel I., Sabater-Lleal, Maria, Chen, Ming-Huei, Huffman, Jennifer E., Steri, Maristella, Tang, Weihong, Teumer, Alexander, Marioni, Riccardo E., Grossmann, Vera, Hottenga, Jouke J., Trompet, Stella, Müller-Nurasyid, Martina, Zhao, Jing Hua, Brody, Jennifer A., Kleber, Marcus E., Guo, Xiuqing, Wang, Jie Jin, Auer, Paul L., Attia, John R., Yanek, Lisa R., Ahluwalia, Tarunveer S., Lahti, Jari, Venturini, Cristina, Tanaka, Toshiko, Bielak, Lawrence F., Joshi, Peter K., Rocanin-Arjo, Ares, Kolcic, Ivana, Navarro, Pau, Rose, Lynda M., Oldmeadow, Christopher, Riess, Helene, Mazur, Johanna, Basu, Saonli, Goel, Anuj, Yang, Qiong, Ghanbari, Mohsen, Willemsen, Gonneke, Rumley, Ann, Fiorillo, Edoardo, de Craen, Anton J. M., Grotevendt, Anne, Scott, Robert, Taylor, Kent D., Delgado, Graciela E., Yao, Jie, Kifley, Annette, Kooperberg, Charles, Qayyum, Rehan, Lopez, Lorna M., Berentzen, Tina L., Räikkönen, Katri, Mangino, Massimo, Bandinelli, Stefania, Peyser, Patricia A., Wild, Sarah, Trégouët, David-Alexandre, Wright, Alan F., Marten, Jonathan, Zemunik, Tatijana, Morrison, Alanna C., Sennblad, Bengt, Tofler, Geoffrey, de Maat, Moniek P. M., de Geus, Eco J. C., Lowe, Gordon D., Zoledziewska, Magdalena, Sattar, Naveed, Binder, Harald, Völker, Uwe, Waldenberger, Melanie, Khaw, Kay-Tee, Mcknight, Barbara, Huang, Jie, Jenny, Nancy S., Holliday, Elizabeth G., Qi, Lihong, Mcevoy, Mark G., Becker, Diane M., Starr, John M., Sarin, Antti-Pekka, Hysi, Pirro G., Hernandez, Dena G., Jhun, Min A., Campbell, Harry, Hamsten, Anders, Rivadeneira, Fernando, Mcardle, Wendy L., Slagboom, P. Eline, Zeller, Tanja, Koenig, Wolfgang, Psaty, Bruce M., Haritunians, Talin, Liu, Jingmin, Palotie, Aarno, Uitterlinden, André G., Stott, David J., Hofman, Albert, Franco, Oscar H., Polasek, Ozren, Rudan, Igor, Morange, Pierre-Emmanuel, Wilson, James F., Kardia, Sharon L. R., Ferrucci, Luigi, Spector, Tim D., Eriksson, Johan G., Hansen, Torben, Deary, Ian J., Becker, Lewis C., Scott, Rodney J., Mitchell, Paul, März, Winfried, Wareham, Nick J., Peters, Annette, Greinacher, Andreas, Wild, Philipp S., Jukema, J. Wouter, Boomsma, Dorret I., Hayward, Caroline, Cucca, Francesco, Tracy, Russell, Watkins, Hugh, Reiner, Alex P., Folsom, Aaron R., Ridker, Paul M., O'Donnell, Christopher J., Smith, Nicholas L., Strachan, David P., Dehghan, Abbas, de Vries, Paul S., Chasman, Daniel I., Sabater-Lleal, Maria, Chen, Ming-Huei, Huffman, Jennifer E., Steri, Maristella, Tang, Weihong, Teumer, Alexander, Marioni, Riccardo E., Grossmann, Vera, Hottenga, Jouke J., Trompet, Stella, Müller-Nurasyid, Martina, Zhao, Jing Hua, Brody, Jennifer A., Kleber, Marcus E., Guo, Xiuqing, Wang, Jie Jin, Auer, Paul L., Attia, John R., Yanek, Lisa R., Ahluwalia, Tarunveer S., Lahti, Jari, Venturini, Cristina, Tanaka, Toshiko, Bielak, Lawrence F., Joshi, Peter K., Rocanin-Arjo, Ares, Kolcic, Ivana, Navarro, Pau, Rose, Lynda M., Oldmeadow, Christopher, Riess, Helene, Mazur, Johanna, Basu, Saonli, Goel, Anuj, Yang, Qiong, Ghanbari, Mohsen, Willemsen, Gonneke, Rumley, Ann, Fiorillo, Edoardo, de Craen, Anton J. M., Grotevendt, Anne, Scott, Robert, Taylor, Kent D., Delgado, Graciela E., Yao, Jie, Kifley, Annette, Kooperberg, Charles, Qayyum, Rehan, Lopez, Lorna M., Berentzen, Tina L., Räikkönen, Katri, Mangino, Massimo, Bandinelli, Stefania, Peyser, Patricia A., Wild, Sarah, Trégouët, David-Alexandre, Wright, Alan F., Marten, Jonathan, Zemunik, Tatijana, Morrison, Alanna C., Sennblad, Bengt, Tofler, Geoffrey, de Maat, Moniek P. M., de Geus, Eco J. C., Lowe, Gordon D., Zoledziewska, Magdalena, Sattar, Naveed, Binder, Harald, Völker, Uwe, Waldenberger, Melanie, Khaw, Kay-Tee, Mcknight, Barbara, Huang, Jie, Jenny, Nancy S., Holliday, Elizabeth G., Qi, Lihong, Mcevoy, Mark G., Becker, Diane M., Starr, John M., Sarin, Antti-Pekka, Hysi, Pirro G., Hernandez, Dena G., Jhun, Min A., Campbell, Harry, Hamsten, Anders, Rivadeneira, Fernando, Mcardle, Wendy L., Slagboom, P. Eline, Zeller, Tanja, Koenig, Wolfgang, Psaty, Bruce M., Haritunians, Talin, Liu, Jingmin, Palotie, Aarno, Uitterlinden, André G., Stott, David J., Hofman, Albert, Franco, Oscar H., Polasek, Ozren, Rudan, Igor, Morange, Pierre-Emmanuel, Wilson, James F., Kardia, Sharon L. R., Ferrucci, Luigi, Spector, Tim D., Eriksson, Johan G., Hansen, Torben, Deary, Ian J., Becker, Lewis C., Scott, Rodney J., Mitchell, Paul, März, Winfried, Wareham, Nick J., Peters, Annette, Greinacher, Andreas, Wild, Philipp S., Jukema, J. Wouter, Boomsma, Dorret I., Hayward, Caroline, Cucca, Francesco, Tracy, Russell, Watkins, Hugh, Reiner, Alex P., Folsom, Aaron R., Ridker, Paul M., O'Donnell, Christopher J., Smith, Nicholas L., Strachan, David P., and Dehghan, Abbas

Abstract

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

Published
2015

50. Characterization of European-ancestry NAFLD-Associated Variants in Individuals of African and Hispanic Descent

Author

Palmer, Nicholette D, Musani, Solomon K, Yerges-Armstrong, Laura M, Feitosa, Mary F, Bielak, Lawrence F, Hernaez, Ruben, Kahali, Bratati, Carr, J Jeffrey, Harris, Tamara B, Jhun, Min A, Kardia, Sharon LR, Langefeld, Carl D, Mosley, Thomas H, Norris, Jill M, Smith, Albert V, Taylor, Herman A, Wagenknecht, Lynne E, Liu, Jiankang, Borecki, Ingrid B, Peyser, Patricia A, and Speliotes, Elizabeth K

Subjects
Adult, Male, Black People, Genetic Variation, Membrane Proteins, Nerve Tissue Proteins, Hispanic or Latino, Lipase, Middle Aged, Article, White People, Cohort Studies, Fatty Liver, Chondroitin Sulfate Proteoglycans, Gene Frequency, Non-alcoholic Fatty Liver Disease, Phosphoprotein Phosphatases, Humans, Female, Genetic Predisposition to Disease, Lectins, C-Type, Lysophospholipase, Neurocan, Adaptor Proteins, Signal Transducing, Aged
Abstract

Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African- and/or Hispanic-Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African American (n = 3,124) and one Hispanic American (n = 849) cohorts. All analyses controlled for variation in age, age(2) , gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR, and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9 kg/m(2) , respectively. Hepatic steatosis was 0.20-0.34 heritable in African- and Hispanic-American families (P 0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1.Multiple genetic variants are associated with hepatic steatosis across ancestries. This explains a substantial proportion of the genetic predisposition in African- and Hispanic-Americans. Missense variants in PNPLA3 and GCKR are likely functional across multiple ancestries.

Published
2013

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