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1. Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative.

Author: Butler-Laporte, Guillaume, Povysil, Gundula, Kosmicki, Jack, Cirulli, Elizabeth, Drivas, Theodore, Furini, Simone, Saad, Chadi, Schmidt, Axel, Olszewski, Pawel, Korotko, Urszula, Quinodoz, Mathieu, Çelik, Elifnaz, Kundu, Kousik, Walter, Klaudia, Jung, Junghyun, Stockwell, Amy, Sloofman, Laura, Jordan, Daniel, Thompson, Ryan, Del Valle, Diane, Simons, Nicole, Cheng, Esther, Sebra, Robert, Schadt, Eric, Kim-Schulze, Seunghee, Gnjatic, Sacha, Merad, Miriam, Buxbaum, Joseph, Beckmann, Noam, Charney, Alexander, Przychodzen, Bartlomiej, Chang, Timothy, Pottinger, Tess, Shang, Ning, Brand, Fabian, Fava, Francesca, Mari, Francesca, Chwialkowska, Karolina, Niemira, Magdalena, Pula, Szymon, Baillie, J, Stuckey, Alex, Salas, Antonio, Bello, Xabier, Pardo-Seco, Jacobo, Gómez-Carballa, Alberto, Rivero-Calle, Irene, Martinón-Torres, Federico, Ganna, Andrea, Karczewski, Konrad, Veerapen, Kumar, Bourgey, Mathieu, Bourque, Guillaume, Eveleigh, Robert, Forgetta, Vincenzo, Morrison, David, Langlais, David, Lathrop, Mark, Mooser, Vincent, Nakanishi, Tomoko, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklos, Marincevic-Zuniga, Yanara, Nordlund, Jessica, Schiabor Barrett, Kelly, Lee, William, Bolze, Alexandre, White, Simon, Riffle, Stephen, Tanudjaja, Francisco, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Casadei, Nicolas, Motameny, Susanne, Alaamery, Manal, Massadeh, Salam, Aljawini, Nora, Almutairi, Mansour, Arabi, Yaseen, Alqahtani, Saleh, Al Harthi, Fawz, Almutairi, Amal, Alqubaishi, Fatima, Alotaibi, Sarah, Binowayn, Albandari, Alsolm, Ebtehal, El Bardisy, Hadeel, Fawzy, Mohammad, Cai, Fang, Soranzo, Nicole, Butterworth, Adam, Geschwind, Daniel, Arteaga, Stephanie, Stephens, Alexis, Butte, Manish, Boutros, Paul, Yamaguchi, Takafumi, and Tao, Shu
Subjects: Humans, Exome, Genome-Wide Association Study, COVID-19, Genetic Predisposition to Disease, Toll-Like Receptor 7, SARS-CoV-2
Abstract: Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
Published: 2022

2. Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial

Author: Tardif, Jean Claude, Pfeffer, Marc A, Kouz, Simon, Koenig, Wolfgang, Maggioni, Aldo P, McMurray, John JV, Mooser, Vincent, Waters, David D, Grégoire, Jean C, L’Allier, Philippe L, Jukema, J Wouter, White, Harvey D, Heinonen, Therese, Black, Donald M, Laghrissi-Thode, Fouzia, Levesque, Sylvie, Guertin, Marie Claude, Dubé, Marie Pierre, and Investigators, for the dal-GenE
Subjects: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Trials and Supportive Activities, Clinical Research, Cardiovascular, Genetics, Heart Disease - Coronary Heart Disease, Heart Disease, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Acute Coronary Syndrome, Adenylyl Cyclases, Amides, Anticholesteremic Agents, Double-Blind Method, Esters, Heart Arrest, Humans, Myocardial Infarction, Pharmacogenetics, Retrospective Studies, Stroke, Sulfhydryl Compounds, Precision medicine, Atherosclerosis, Myocardial infarction, CETP, Adenylate cyclase type 9, dal-GenE Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract: AimsIn a retrospective analysis of dal-Outcomes, the effect of dalcetrapib on cardiovascular events was influenced by an adenylate cyclase type 9 (ADCY9) gene polymorphism. The dal-GenE study was conducted to test this pharmacogenetic hypothesis.Methods and resultsdal-GenE was a double-blind trial in patients with an acute coronary syndrome within 1-3 months and the AA genotype at variant rs1967309 in the ADCY9 gene. A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from randomization to first occurrence of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 39.9 months, the primary endpoint occurred in 292 (9.5%) of 3071 patients in the dalcetrapib group and 327 (10.6%) of 3076 patients in the placebo group [hazard ratio 0.88; 95% confidence interval (CI) 0.75-1.03; P = 0.12]. The hazard ratios for the components of the primary endpoint were 0.79 (95% CI 0.65-0.96) for myocardial infarction, 0.92 (95% CI 0.64-1.33) for stroke, 1.21 (95% CI 0.91-1.60) for death from cardiovascular causes, and 2.33 (95% CI 0.60-9.02) for resuscitated cardiac arrest. In a pre-specified on-treatment sensitivity analysis, the primary endpoint event rate was 7.8% (236/3015) in the dalcetrapib group and 9.3% (282/3031) in the placebo group (hazard ratio 0.83; 95% CI 0.70-0.98).ConclusionDalcetrapib did not significantly reduce the risk of occurrence of the primary endpoint of ischaemic cardiovascular events at end of study. A new trial would be needed to test the pharmacogenetic hypothesis that dalcetrapib improves the prognosis of patients with the AA genotype.Clinical trial registrationTrial registration dal-GenE ClinicalTrials.gov Identifier: NCT02525939.
Published: 2022

3. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Cuellar-Partida, Gabriel, Tung, Joyce Y, Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A, Barroso, Inês, Beckmann, Jacques S, Boks, Marco P, Boomsma, Dorret I, Boyd, Heather A, Breteler, Monique MB, Campbell, Harry, Chasman, Daniel I, Cherkas, Lynn F, Davies, Gail, de Geus, Eco JC, Deary, Ian J, Deloukas, Panos, Dick, Danielle M, Duffy, David L, Eriksson, Johan G, Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D, Han, Jiali, Hansen, Thomas F, Hartmann, Annette M, Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A, Hirschhorn, Joel N, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Liang-Dar, Ikram, M Arfan, Kaprio, Jaakko, Kemp, John P, Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth JF, Luciano, Michelle, Magnusson, Sigurdur H, Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G, McArdle, Wendy L, McCarthy, Mark I, Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A, Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R, O’Connell, Kevin S, Ophoff, Roel A, Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda WJH, Polasek, Ozren, Pramstaller, Peter P, Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H, Smith, George Davey, Smoller, Jordan W, Soranzo, Nicole, Spector, Tim D, Pourcain, Beate St, Starr, John M, Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J, Uitterlinden, André G, van Duijn, Cornelia M, van Rooij, Frank JA, Vink, Jaqueline M, Vollenweider, Peter, Vuoksimaa, Eero, and Waeber, Gérard
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Human Genome, Mental Health, Brain Disorders, Neurosciences, Schizophrenia, Genetics, 2.1 Biological and endogenous factors, Aetiology, Mental health, Adult, Aged, Female, Functional Laterality, Gene Frequency, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Sex Factors, Biomedical and clinical sciences, Health sciences
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P
Published: 2021

4. Study design of Dal-GenE, a pharmacogenetic trial targeting reduction of cardiovascular events with dalcetrapib

Author: Tardif, Jean-Claude, Dubé, Marie-Pierre, Pfeffer, Marc A, Waters, David D, Koenig, Wolfgang, Maggioni, Aldo P, McMurray, John JV, Mooser, Vincent, White, Harvey D, Heinonen, Therese, Black, Donald M, Guertin, Marie-Claude, and Investigators, for the dal-GenE
Subjects: Genetics, Heart Disease - Coronary Heart Disease, Heart Disease, Cardiovascular, Prevention, Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Adenylyl Cyclases, Amides, Anticholesteremic Agents, Atherosclerosis, Dose-Response Relationship, Drug, Double-Blind Method, Esters, Female, Follow-Up Studies, Genetic Testing, Genome-Wide Association Study, Genotype, Global Health, Humans, Incidence, Male, Middle Aged, Pharmacogenetics, Polymorphism, Genetic, Precision Medicine, Prognosis, Prospective Studies, Retrospective Studies, Sulfhydryl Compounds, dal-GenE Investigators, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology
Abstract: The objectives of precision medicine are to better match patient characteristics with the therapeutic intervention to optimize the chances of beneficial actions while reducing the exposure to unneeded adverse drug experiences. In a retrospective genome-wide association study of the overall neutral placebo-controlled dal-Outcomes trial, the effect of the cholesteryl ester transfer protein (CETP) modulator dalcetrapib on the composite of cardiovascular death, myocardial infarction or stroke was found to be influenced by a polymorphism in the adenylate cyclase type 9 (ADCY9) gene. Whereas patients with the AA genotype at position rs1967309 experienced fewer cardiovascular events with dalcetrapib, those with the GG genotype had an increased rate and the heterozygous AG genotype exhibited no difference from placebo. Measurements of cholesterol efflux and C-reactive protein (CRP) offered directionally supportive genotype-specific findings. In a separate, smaller, placebo-controlled trial, regression of ultrasonography-determined carotid intimal-medial thickness was only observed in dalcetrapib-treated patients with the AA genotype. Collectively, these observations led to the hypothesis that the cardiovascular effects of dalcetrapib may be pharmacogenetically determined, with a favorable benefit-risk ratio only for patients with this specific genotype. We describe below the design of dal-GenE, a precision medicine, placebo-controlled clinical outcome trial of dalcetrapib in patients with a recent acute myocardial infarction with the unique feature of selecting only those with the AA genotype at rs1967309 in the ADCY9 gene.
Published: 2020

5. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Author: Dastani, Zari, Hivert, Marie-France, Timpson, Nicholas, Perry, John RB, Yuan, Xin, Scott, Robert A, Henneman, Peter, Heid, Iris M, Kizer, Jorge R, Lyytikäinen, Leo-Pekka, Fuchsberger, Christian, Tanaka, Toshiko, Morris, Andrew P, Small, Kerrin, Isaacs, Aaron, Beekman, Marian, Coassin, Stefan, Lohman, Kurt, Qi, Lu, Kanoni, Stavroula, Pankow, James S, Uh, Hae-Won, Wu, Ying, Bidulescu, Aurelian, Rasmussen-Torvik, Laura J, Greenwood, Celia MT, Ladouceur, Martin, Grimsby, Jonna, Manning, Alisa K, Liu, Ching-Ti, Kooner, Jaspal, Mooser, Vincent E, Vollenweider, Peter, Kapur, Karen A, Chambers, John, Wareham, Nicholas J, Langenberg, Claudia, Frants, Rune, Willems-Vandijk, Ko, Oostra, Ben A, Willems, Sara M, Lamina, Claudia, Winkler, Thomas W, Psaty, Bruce M, Tracy, Russell P, Brody, Jennifer, Chen, Ida, Viikari, Jorma, Kähönen, Mika, Pramstaller, Peter P, Evans, David M, St Pourcain, Beate, Sattar, Naveed, Wood, Andrew R, Bandinelli, Stefania, Carlson, Olga D, Egan, Josephine M, Böhringer, Stefan, van Heemst, Diana, Kedenko, Lyudmyla, Kristiansson, Kati, Nuotio, Marja-Liisa, Loo, Britt-Marie, Harris, Tamara, Garcia, Melissa, Kanaya, Alka, Haun, Margot, Klopp, Norman, Wichmann, H-Erich, Deloukas, Panos, Katsareli, Efi, Couper, David J, Duncan, Bruce B, Kloppenburg, Margreet, Adair, Linda S, Borja, Judith B, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, Wilson, James G, Musani, Solomon, Guo, Xiuqing, Johnson, Toby, Semple, Robert, Teslovich, Tanya M, Allison, Matthew A, Redline, Susan, Buxbaum, Sarah G, Mohlke, Karen L, Meulenbelt, Ingrid, Ballantyne, Christie M, Dedoussis, George V, Hu, Frank B, Liu, Yongmei, Paulweber, Bernhard, Spector, Timothy D, Slagboom, P Eline, Ferrucci, Luigi, and Jula, Antti
Subjects: DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Humans, Diabetes Mellitus, Type 2, Insulin Resistance, Genetic Predisposition to Disease, Glucose Tolerance Test, Waist-Hip Ratio, Gene Expression, Polymorphism, Single Nucleotide, African Americans, Asian Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Adiponectin, Cholesterol, HDL, Metabolic Networks and Pathways, Genome-Wide Association Study, Diabetes Mellitus, Type 2, Polymorphism, Single Nucleotide, Cholesterol, HDL, Genetics, Developmental Biology
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p
Published: 2012

6. Circulating proteins to predict COVID-19 severity

Author: Su, Chen-Yang, Zhou, Sirui, Gonzalez-Kozlova, Edgar, Butler-Laporte, Guillaume, Brunet-Ratnasingham, Elsa, Nakanishi, Tomoko, Jeon, Wonseok, Morrison, David R, Laurent, Laetitia, Afilalo, Jonathan, Afilalo, Marc, Henry, Danielle, Chen, Yiheng, Carrasco-Zanini, Julia, Farjoun, Yossi, Pietzner, Maik, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Moussa, Yara, DeLuca, Chantal, Duggan, Naomi, Schurr, Erwin, Brassard, Nathalie, Durand, Madeleine, Del Valle, Diane Marie, Thompson, Ryan, Cedillo, Mario A, Schadt, Eric, Nie, Kai, Simons, Nicole W, Mouskas, Konstantinos, Zaki, Nicolas, Patel, Manishkumar, Xie, Hui, Harris, Jocelyn, Marvin, Robert, Cheng, Esther, Tuballes, Kevin, Argueta, Kimberly, Scott, Ieisha, Mount Sinai COVID-19 Biobank Team, Greenwood, Celia MT, Paterson, Clare, Hinterberg, Michael A, Langenberg, Claudia, Forgetta, Vincenzo, Pineau, Joelle, Mooser, Vincent, Marron, Thomas, Beckmann, Noam D, Kim-Schulze, Seunghee, Charney, Alexander W, Gnjatic, Sacha, Kaufmann, Daniel E, Merad, Miriam, Richards, J Brent, and Apollo - University of Cambridge Repository
Subjects: Risk Factors, Disease Progression, Humans, COVID-19, Proteins, Retrospective Studies
Abstract: Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.
Published: 2023

7. A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity

Author: Zhou, Sirui, Butler-Laporte, Guillaume, Nakanishi, Tomoko, Morrison, David R, Afilalo, Jonathan, Afilalo, Marc, Laurent, Laetitia, Pietzner, Maik, Kerrison, Nicola, Zhao, Kaiqiong, Brunet-Ratnasingham, Elsa, Henry, Danielle, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Bouab, Meriem, Petitjean, Louis, Guzman, Charlotte, Xue, Xiaoqing, Tselios, Chris, Vulesevic, Branka, Adeleye, Olumide, Abdullah, Tala, Almamlouk, Noor, Chen, Yiheng, Chassé, Michaël, Durand, Madeleine, Paterson, Clare, Normark, Johan, Frithiof, Robert, Lipcsey, Miklós, Hultström, Michael, Greenwood, Celia MT, Zeberg, Hugo, Langenberg, Claudia, Thysell, Elin, Pollak, Michael, Mooser, Vincent, Forgetta, Vincenzo, Kaufmann, Daniel E, Richards, J Brent, Butler-Laporte, Guillaume [0000-0001-5388-0396], Nakanishi, Tomoko [0000-0001-9510-5646], Morrison, David R [0000-0001-8380-3615], Brunet-Ratnasingham, Elsa [0000-0002-3613-1315], Afrasiabi, Zaman [0000-0003-4395-5168], Rezk, Nardin [0000-0001-5358-7704], Petitjean, Louis [0000-0002-9223-5100], Guzman, Charlotte [0000-0002-2979-4436], Frithiof, Robert [0000-0003-2278-7951], Hultström, Michael [0000-0003-4675-1099], Greenwood, Celia MT [0000-0002-2427-5696], Langenberg, Claudia [0000-0002-5017-7344], Kaufmann, Daniel E [0000-0003-4467-136X], Richards, J Brent [0000-0002-3746-9086], and Apollo - University of Cambridge Repository
Subjects: Aged, 80 and over, Male, SARS-CoV-2, Quantitative Trait Loci, COVID-19, Mendelian Randomization Analysis, Middle Aged, Interleukin-10 Receptor beta Subunit, Severity of Illness Index, White People, Case-Control Studies, 2',5'-Oligoadenylate Synthetase, Animals, Humans, Protein Isoforms, Female, Genetic Predisposition to Disease, Aged, Neanderthals
Abstract: To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10-8), hospitalization (OR = 0.61, P = 8 × 10-8) and susceptibility (OR = 0.78, P = 8 × 10-6). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case-control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development.
Published: 2021

8. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Cuellar-Partida, Gabriel, Tung, Joyce Y, Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A, Barroso, Inês, Beckmann, Jacques S, Boks, Marco P, Boomsma, Dorret I, Boyd, Heather A, Breteler, Monique MB, Campbell, Harry, Chasman, Daniel I, Cherkas, Lynn F, Davies, Gail, De Geus, Eco JC, Deary, Ian J, Deloukas, Panos, Dick, Danielle M, Duffy, David L, Eriksson, Johan G, Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D, Han, Jiali, Hansen, Thomas F, Hartmann, Annette M, Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A, Hirschhorn, Joel N, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Liang-Dar, Ikram, M Arfan, Kaprio, Jaakko, Kemp, John P, Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth JF, Luciano, Michelle, Magnusson, Sigurdur H, Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G, McArdle, Wendy L, McCarthy, Mark I, Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A, Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R, O'Connell, Kevin S, Ophoff, Roel A, Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda WJH, Polasek, Ozren, Pramstaller, Peter P, Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H, Smith, George Davey, Smoller, Jordan W, Soranzo, Nicole, Spector, Tim D, Pourcain, Beate St, Starr, John M, Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J, Uitterlinden, André G, Van Duijn, Cornelia M, Van Rooij, Frank JA, Vink, Jaqueline M, Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J, Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H-Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F, Wright, Margaret J, Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A, Lindgren, Cecilia M, Mägi, Reedik, Neale, Benjamin M, Evans, David M, and Medland, Sarah E
Subjects: Adult, Male, Genetic Variation, Middle Aged, Polymorphism, Single Nucleotide, Functional Laterality, Linkage Disequilibrium, Quantitative Trait, Heritable, Sex Factors, Gene Frequency, Genetic Loci, Humans, Female, Aged, Genome-Wide Association Study
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
Published: 2020
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9. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author: Wain, Louise V, Verwoert, Germaine C, O'Reilly, Paul F, Shi, Gang, Johnson, Toby, Johnson, Andrew D, Bochud, Murielle, Rice, Kenneth M, Henneman, Peter, Smith, Albert V, Ehret, Georg B, Amin, Najaf, Larson, Martin G, Mooser, Vincent, Hadley, David, Dörr, Marcus, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile JW, Zhao, Jing Hua, Heath, Simon, Laan, Maris, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'an, Arora, Pankaj, Lucas, Gavin, Pirastu, Nicola, Pichler, Irene, Jackson, Anne U, Webster, Rebecca J, Zhang, Feng, Peden, John F, Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I, Trompet, Stella, Bragg-Gresham, Jennifer L, Alizadeh, Behrooz Z, Chambers, John C, Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M, Polašek, Ozren, Boban, Mladen, Nelson, Christopher P, Morrison, Alanna C, Pihur, Vasyl, Ganesh, Santhi K, Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco US, Rivadeneira, Fernando, Sijbrands, Eric JG, Uitterlinden, Andre G, Hwang, Shih-Jen, Vasan, Ramachandran S, Wang, Thomas J, Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, McArdle, Wendy L, Kroemer, Heyo K, Völker, Uwe, Völzke, Henry, Glazer, Nicole L, Taylor, Kent D, Harris, Tamara B, Alavere, Helene, Haller, Toomas, Keis, Aime, Tammesoo, Mari-Liis, Aulchenko, Yurii, Barroso, Inês, Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M, Penninx, Brenda W, Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco, Fabiola M, Facheris, Maurizio, Collins, Francis S, Bergman, Richard N, Beilby, John P, Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Anders, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S, Navarro, Pau, Wild, Sarah H, Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco JC, Willemsen, Gonneke, Parker, Alex N, Rose, Lynda M, Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, LifeLines Cohort Study, Van Der Klauw, Melanie M, Zhang, Weihua, Li, Xinzhong, Scott, James, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thomas, Davies, Gail, Starr, John M, Emilsson, Valur, Plump, Andrew, Lindeman, Jan H, Hoen, Peter AC 'T, König, Inke R, EchoGen Consortium, Felix, Janine F, Clarke, Robert, Hopewell, Jemma C, Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L, Fornage, Myriam, AortaGen Consortium, Mitchell, Gary F, CHARGE Consortium Heart Failure Working Group, Smith, Nicholas L, KidneyGen Consortium, Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, CKDGen Consortium, Cardiogenics Consortium, CardioGram, Samani, Nilesh J, Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J, Wichmann, H-Erich, Raitakari, Olli T, Palmas, Walter, Kooner, Jaspal S, Stolk, Ronald P, Jukema, J Wouter, Wright, Alan F, Boomsma, Dorret I, Bandinelli, Stefania, Gyllensten, Ulf B, Wilson, James F, Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D, Palmer, Lyle J, Tuomilehto, Jaakko, Pfeufer, Arne, Gasparini, Paolo, Siscovick, David, Altshuler, David, Loos, Ruth JF, Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J, Oostra, Ben A, Metspalu, Andres, Launer, Lenore, Rettig, Rainer, Strachan, David P, Beckmann, Jacques S, Witteman, Jacqueline CM, Erdmann, Jeanette, Van Dijk, Ko Willems, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M, Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R, Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B, Psaty, Bruce M, Caulfield, Mark J, Rao, Dabeeru C, Tobin, Martin D, Elliott, Paul, and Van Duijn, Cornelia M
Subjects: Genetic Loci, Case-Control Studies, Hypertension, Humans, Blood Pressure, cardiovascular diseases, Arteries, Polymorphism, Single Nucleotide, Linkage Disequilibrium, circulatory and respiratory physiology, Follow-Up Studies, Genome-Wide Association Study
Abstract: Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
Published: 2018
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10. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author: Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcus, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. W., Zhao, Jing Hua, Heath, Simon, Laan, Maris, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'An, Arora, Pankaj, Lucas, Gavin, Pirastu, Nicola, Pichler, Irene, Jackson, Anne U., Webster, Rebecca J., Zhang, Feng, Peden, John F., Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I., Trompet, Stella, Bragg-Gresham, Jennifer L., Alizadeh, Behrooz Z., Chambers, John C., Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M., Polašek, Ozren, Boban, Mladen, Nelson, Christopher P., Morrison, Alanna C., Pihur, Vasyl, Ganesh, Santhi K., Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco U. S., Rivadeneira, Fernando, Sijbrands, Eric J. G., Uitterlinden, Andre G., Hwang, Shih-Jen, Vasan, Ramachandran S., Wang, Thomas J., Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, McArdle, Wendy L., Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Glazer, Nicole L., Taylor, Kent D., Harris, Tamara B., Alavere, Helene, Haller, Toomas, Keis, Aime, Tammesoo, Mari-Liis, Aulchenko, Yurii, Barroso, In S., Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M., Penninx, Brenda W., Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco M, Fabiola, Facheris, Maurizio, Collins, Francis S., Bergman, Richard N., Beilby, John P., Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Anders, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S., Navarro, Pau, Wild, Sarah H., Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco J. C., Willemsen, Gonneke, Parker, Alex N., Rose, Lynda M., Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, Van Der Klauw, Melanie M., Zhang, Weihua, Li, Xinzhong, Scott, James, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thomas, Davies, Gail, Starr, John M., Emilsson, Valur, Plump, Andrew, Lindeman, Jan H., Hoen, Peter A. C. T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Gasparini, Paolo, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andres, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. 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Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Coresh J, Schmidt R, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Felix SB, Watzinger N, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Reffelmann T, Redfield MM, Werdan K, Arnett DK, Blettner M, Friedrich N, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic N, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Vollenweider P, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Lightstone L, Scott J, Navis G, Elliott P, Kooner JS., Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), University of Leicester, Department of Genetics [Leicester], Erasmus University Rotterdam, Netherlands Genomics Initiative, Department of Epidemiology and Biostatistics, School of Public Health, Zahedan University of Medical Sciences, Washington University in Saint Louis (WUSTL), Queen Mary University of London (QMUL), National Heart, Lung and Blood Institute, Partenaires INRAE, Centre Hospitalier Universitaire Vaudois (CHUV), Université de Lausanne = University of Lausanne (UNIL), Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Leiden University Medical Center (LUMC), Universiteit Leiden, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland [Reykjavik], Johns Hopkins University, School of Medicine, Hôpitaux Universitaires de Genève (HUG), Department of Epidemiology, The Netherlands Cancer Institute, Department of Mathematics, Boston University [Boston] (BU), GlaxoSmithKline, Division of Community Health Sciences, St. George's, University of South Florida [Tampa] (USF), Universität Greifswald - University of Greifswald, University of Washington [Seattle], University of Tartu, Institute of Molecular and Cell Biology, Medical Research Council, Institut de Génomique, Centre National de Génotypage, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University Medical Center Groningen, Department of Genetics, University Medical Center Groningen [Groningen] (UMCG), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Massachusetts General Hospital [Boston], Centro de Regulación Genómica (CRG), Universitat Pompeu Fabra [Barcelona] (UPF), Università degli studi di Trieste = University of Trieste, Universität zu Lübeck = University of Lübeck [Lübeck], Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, The University of Western Australia (UWA), Department of Twin Research and Genetic Epidemiology, King's College London, London, University of Oxford, Medical University Graz, National Institute on Aging, Centre for population Health Sciences, University of Edinburgh, Uppsala University, Vrije Universiteit Amsterdam [Amsterdam] (VU), Western General Hospital, Harvard Medical School [Boston] (HMS), Brigham and Women's Hospital [Boston], University of Michigan System, University of Groningen, Ealing Hospital, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Medical Genetics Institute, Cedars-Sinai Medical Center, University of Tampere, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Split, The University of Texas Health Science Center at Houston (UTHealth), Johns Hopkins University (JHU), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Swiss Institute of Bioinformatics [Lausanne] (SIB), Finnish Institute of Occupational Health, National Institute of Health and Welfare, University of Oulu, Lapland Central Hospital, University of Bristol [Bristol], Institute for Community Medicine, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), US National Institutes of Health, National Heart, Lung, and Blood Institute, European, Epidemiology, Internal Medicine, Public Health, Clinical Genetics, Université de Lausanne (UNIL), LeidenUniversity Medical Centre, University of Iceland, Università degli studi di Trieste, Universität zu Lübeck [Lübeck], University of Western Australia, University of Oxford [Oxford], VU University Amsterdam, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Human genetics, Psychiatry, EMGO - Mental health, NCA - Anxiety & Depression, Epidemiology and Data Science, Medical Research Council (MRC), Louise V., Wain, Germaine C., Verwoert, Paul F., O'Reilly, Gang, Shi, Toby, Johnson, Andrew D., Johnson, Murielle, Bochud, Kenneth M., Rice, Peter, Henneman, Albert V., Smith, Georg B., Ehret, Najaf, Amin, Martin G., Larson, Vincent, Mooser, David, Hadley, Marcus, Dörr, Joshua C., Bi, Thor, Aspelund, Tõnu, Esko, A. Cecile J. W., Janssen, Jing Hua, Zhao, Simon, Heath, Maris, Laan, Jingyuan, Fu, Giorgio, Pisti, Jian'An, Luan, Pankaj, Arora, Gavin, Luca, Pirastu, Nicola, Irene, Pichler, Anne U., Jackson, Rebecca J., Webster, Feng, Zhang, John F., Peden, Helena, Schmidt, Toshiko, Tanaka, Harry, Campbell, Wilmar, Igl, Yuri, Milaneschi, Jouke Jan, Hottenga, Veronique, Vitart, Daniel I., Chasman, Stella, Trompet, Jennifer L., Bragg Gresham, Behrooz Z., Alizadeh, John C., Chamber, Xiuqing, Guo, Terho, Lehtimäki, Brigitte, Kühnel, Lorna M., Lopez, Ozren, Polašek, Mladen, Boban, Christopher P., Nelson, Alanna C., Morrison, Vasyl, Pihur, Santhi K., Ganesh, Albert, Hofman, Suman, Kundu, Francesco U. S., Mattace Raso, Fernando, Rivadeneira, Eric J. 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Subjects: Netherlands Twin Register (NTR), Linkage disequilibrium, pulse pressure, mean arterial pressure, genome-wide, [SDV]Life Sciences [q-bio], Genome-wide association study, BLOOD-PRESSURE, Blood Pressure, 030204 cardiovascular system & hematology, Linkage Disequilibrium, 0302 clinical medicine, RELEVANCE, CardioGram, Medicine and Health Sciences, Genetics & Heredity, ddc:616, Genetics, 0303 health sciences, Genome-wide association, 11 Medical And Health Sciences, Arteries, ADRENERGIC-RECEPTOR TRAFFICKING, Pulse pressure, EchoGen consortium, Hypertension, HEART-FAILURE, arterial pressure, Case-Control Studie, Life Sciences & Biomedicine, Human, circulatory and respiratory physiology, medicine.medical_specialty, Mean arterial pressure, Arterie, AortaGen Consortium, Cardiogenics consortium, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Article, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Humans, cardiovascular diseases, METAANALYSIS, 030304 developmental biology, Genetic association, Science & Technology, HYPERTENSION, MORTALITY, Case-control study, CARDIOVASCULAR-DISEASE RISK, 06 Biological Sciences, GENE, MICE, Endocrinology, Blood pressure, CKDGen consortium, Genetic Loci, Case-Control Studies, KidneyGen consortium, CHARGE Consortium Heart Failure Working Group, LifeLines Cohort Study, Developmental Biology, Follow-Up Studies, Genome-Wide Association Study
Abstract: Les affiliations des 100 premiers auteurs sont renseignées dans la notice. Les affiliations des autres auteurs sont disponibles à la fin de la publication.; International audience; Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
Published: 2016

11. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author: Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sober, Siim, Parsa, Afshin, Luan, Jian'an, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Hoang Nguyen, Khanh-Dung, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., Cooper, Matthew N., Platou, Carl G. P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S. P. M., Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., O'Connell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Kardia, Sharon L., Morrison, Alanna C., Hernandez, Dena, Najjar, Samer, McArdle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N. 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T., Mosley, Thomas H., Seshadri, Sudha, Shrine, Nick R. G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Anders, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U. S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Twee-HeeOng, Rick, Dörr, Marcus, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Panos, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Janos, Kranthi Kumar, M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, F. Gerald R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charles, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Maris, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Shyong Tai, E., Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. G., Altshuler, David, Loos, Ruth J. F., Shuldiner, Alan R., Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G., Wareham, Nicholas J., Gudnason, Vilmundur, Rotter, Jerome I., Rettig, Rainer, Uda, Manuela, Strachan, David P., Witteman, Jacqueline C. M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Vasan, Ramachandran S., Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., Johnson, Toby, Tang H, Knowles J, Hlatky M, Fortmann S, Assimes TL, Quertermous T, Go A, Iribarren C, Absher D, Risch N, Meyers R, Sidney S, Ziegler A, Schillert A, Bickel C, Sinning C, Rupprecht HJ, Lackner K, Wild P, Schnabel R, Blankenberg S, Zeller T, Münzel T, Perret C, Cambien F, Tiret L, Nicaud V, Proust C, Dehghan A, Hofman A, Uitterlinden A, van Duijn C, Levy D, Whitteman J, Cupples LA, Demissie-Banjaw S, Ramachandran V, Smith A, Gudnason V, Boerwinkle E, Folsom A, Morrison A, Psaty BM, Chen IY, Rotter JI, Bis J, Volcik K, Rice K, Taylor KD, Marciante K, Smith N, Glazer N, Heckbert S, Harris T, Lumley T, Kong A, Thorleifsson G, Thorgeirsson G, Holm H, Gulcher JR, Stefansson K, Andersen K, Gretarsdottir S, Thorsteinsdottir U, Preuss M, Schreiber S, Meitinger T, König IR, Lieb W, Hengstenberg C, Schunkert H, Erdmann J, Fisher M, Grosshennig A, Medack A, Stark K, Linsel-Nitschke P, Bruse P, Aherrahrou Z, Peters A, Loley C, Willenborg C, Nahrstedt J, Freyer J, Gulde S, Doering A, Meisinger C, Wichmann HE, Klopp N, Illig T, Meinitzer A, Tomaschitz A, Halperin E, Dobnig H, Scharnagl H, Kleber M, Laaksonen R, Pilz S, Grammer TB, Stojakovic T, Renner W, März W, Böhm BO, Winkelmann BR, Winkler K, Hoffmann M, O'Donnell CJ, Voight BF, Altshuler D, Siscovick DS, Musunuru K, Peltonen L, Barbalic M, Melander O, Elosua R, Kathiresan S, Schwartz SM, Salomaa V, Guiducci C, Burtt N, Gabriel SB, Stewart AF, Wells GA, Chen L, Jarinova O, Roberts R, McPherson R, Dandona S, Pichard AD, Rader DJ, Devaney J, Lindsay JM, Kent KM, Qu L, Satler L, Burnett MS, Li M, Reilly MP, Wilensky R, Waksman R, Epstein S, Mattha W, Knouf CW, Waterworth DM, Hakonarson HH, Walker M, Mooser V, Hall AS, Balmforth AJ, Wright BJ, Nelson C, Thompson JR, Samani NJ, Braund PS, Ball SG, Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Rosamond WD, Rivadeneira F, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Wang YA, Stricker B, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Heckbert SR, Fox ER, Uitterlinden AG, Willerson JT, van Duijn CM, Witteman JC, Vasan RS, Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Parsa A, Gao X, Yang Q, Smith AV, O'Connell JR, Schmidt H, Tanaka T, Isaacs A, Ketkar S, Hwang SJ, Johnson A, Teumer A, Paré G, Atkinson EJ, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Aspelund T, Eiriksdottir G, Launer LJ, Harris TB, Rampersaud E, Mitchell BD, Arking DE, Struchalin M, Cavalieri M, Singleton A, Giallauria, Francesco, Metter J, de Boer J, Siscovick D, Zillikens MC, Oostra BA, Feitosa M, Province M, de Andrade M, Turne ST, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Liu Y, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Shuldiner AR, Coresh J, Schmidt R, Ferrucci L, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Vasan R, Felix SB, Watzinger N, Larson MG, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Stricker BH, Reffelmann T, Redfield MM, Werdan K, Mitchell GF, Arnett D, Blettner M, Friedrich N, Benjamin EJ, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic T, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Sanna S, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Uda M, Vollenweider P, Wallace C, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Abecasis GR, Lightstone L, Scott J, Navis G, Elliot P, Kooner JS., AII - Amsterdam institute for Infection and Immunity, Nephrology, Epidemiologie, RS: CARIM School for Cardiovascular Diseases, Epidemiology, Medical Microbiology & Infectious Diseases, Radiology & Nuclear Medicine, Cardiology, Internal Medicine, Clinical Genetics, Erasmus MC other, Obstetrics & Gynecology, International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Zhao, Jing Hua [0000-0003-4930-3582], Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Khaw, Kay-Tee [0000-0002-8802-2903], Danesh, John [0000-0003-1158-6791], Soranzo, Nicole [0000-0003-1095-3852], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Clinical Pharmacology and The Genome Centre, Queen Mary University of London (QMUL), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Center for Human Genetic Research, Massachusetts General Hospital [Boston], Program in Medical and Population Genetics, Harvard University-Massachusetts Institute of Technology (MIT), Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sober, Siim, Parsa, Afshin, Luan, Jian'An, Arora, Pankaj, Dehghan, Abba, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Hoang Nguyen, Khanh-Dung, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., Cooper, Matthew N., Platou, Carl G. P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S. P. M., Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., O'Connell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Kardia, Sharon L., Morrison, Alanna C., Hernandez, Dena, Najjar, Samer, Mcardle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N. M., Lawlor, Debbie A., Beilby, John P., Lawrence, Robert W., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Dreisbach, Albert W., Li, Yali, Hunter Young, J., Bis, Joshua C., Kähönen, Mika, Viikari, Jorma, Adair, Linda S., Lee, Nanette R., Chen, Ming-Huei, Olden, Matthia, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M., Islam, Muhammad, Jafar, Tazeen H., Erdmann, Jeanette, Kulkarni, Smita R., Bornstein, Stefan R., Grässler, Jürgen, Groop, Leif, Voight, Benjamin F., Kettunen, Johanne, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inê, Khaw, Kay-Tee, Weder, Alan B., Hunt, Steven C., Sun, Yan V., Bergman, Richard N., Collins, Francis S., Bonnycastle, Lori L., Scott, Laura J., Stringham, Heather M., Peltonen, Leena, Perola, Marku, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A., Wang, Thomas J., Burton, Paul R., Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K., Rudock, Megan E., Heckbert, Susan R., Smith, Nicholas L., Wiggins, Kerri L., Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margu, Kinra, Sanjay, Prabhakaran, Dorairaj, Tripathy, Vikal, Langefeld, Carl D., Rosengren, Annika, Thelle, Dag S., Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, Mckenzie, Colin A., Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thoma, Wichmann, H. -Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, Jame, Sehmi, Joban S., Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J., Yao, Jie, Kathiresan, Sekar, O'Donnell, Christopher J., Schwartz, Stephen M., Arfan Ikram, M., Longstreth Jr., W. T., Mosley, Thomas H., Seshadri, Sudha, Shrine, Nick R. G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Ander, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U. S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Twee-HeeOng, Rick, Dörr, Marcu, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Pano, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Jano, Kranthi Kumar, M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, F. Gerald R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charle, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Mari, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Shyong Tai, E., Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. G., Altshuler, David, Loos, Ruth J. F., Shuldiner, Alan R., Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G., Wareham, Nicholas J., Gudnason, Vilmundur, Rotter, Jerome I., Rettig, Rainer, Uda, Manuela, Strachan, David P., Witteman, Jacqueline C. M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Vasan, Ramachandran S., Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., Johnson, Toby, Tang, H, Knowles, J, Hlatky, M, Fortmann, S, Assimes, Tl, Quertermous, T, Go, A, Iribarren, C, Absher, D, Risch, N, Meyers, R, Sidney, S, Ziegler, A, Schillert, A, Bickel, C, Sinning, C, Rupprecht, Hj, Lackner, K, Wild, P, Schnabel, R, Blankenberg, S, Zeller, T, Münzel, T, Perret, C, Cambien, F, Tiret, L, Nicaud, V, Proust, C, Dehghan, A, Hofman, A, Uitterlinden, A, van Duijn, C, Levy, D, Whitteman, J, Cupples, La, Demissie-Banjaw, S, Ramachandran, V, Smith, A, Gudnason, V, Boerwinkle, E, Folsom, A, Morrison, A, Psaty, Bm, Chen, Iy, Rotter, Ji, Bis, J, Volcik, K, Rice, K, Taylor, Kd, Marciante, K, Smith, N, Glazer, N, Heckbert, S, Harris, T, Lumley, T, Kong, A, Thorleifsson, G, Thorgeirsson, G, Holm, H, Gulcher, Jr, Stefansson, K, Andersen, K, Gretarsdottir, S, Thorsteinsdottir, U, Preuss, M, Schreiber, S, Meitinger, T, König, Ir, Lieb, W, Hengstenberg, C, Schunkert, H, Erdmann, J, Fisher, M, Grosshennig, A, Medack, A, Stark, K, Linsel-Nitschke, P, Bruse, P, Aherrahrou, Z, Peters, A, Loley, C, Willenborg, C, Nahrstedt, J, Freyer, J, Gulde, S, Doering, A, Meisinger, C, Wichmann, He, Klopp, N, Illig, T, Meinitzer, A, Tomaschitz, A, Halperin, E, Dobnig, H, Scharnagl, H, Kleber, M, Laaksonen, R, Pilz, S, Grammer, Tb, Stojakovic, T, Renner, W, März, W, Böhm, Bo, Winkelmann, Br, Winkler, K, Hoffmann, M, O'Donnell, Cj, Voight, Bf, Altshuler, D, Siscovick, D, Musunuru, K, Peltonen, L, Barbalic, M, Melander, O, Elosua, R, Kathiresan, S, Schwartz, Sm, Salomaa, V, Guiducci, C, Burtt, N, Gabriel, Sb, Stewart, Af, Wells, Ga, Chen, L, Jarinova, O, Roberts, R, Mcpherson, R, Dandona, S, Pichard, Ad, Rader, Dj, Devaney, J, Lindsay, Jm, Kent, Km, Qu, L, Satler, L, Burnett, M, Li, M, Reilly, Mp, Wilensky, R, Waksman, R, Epstein, S, Mattha, W, Knouf, Cw, Waterworth, Dm, Hakonarson, Hh, Walker, M, Mooser, V, Hall, A, Balmforth, Aj, Wright, Bj, Nelson, C, Thompson, Jr, Samani, Nj, Braund, P, Ball, Sg, Smith, Nl, Felix, Jf, Morrison, Ac, Demissie, S, Glazer, Nl, Loehr, Lr, Rosamond, Wd, Rivadeneira, F, Bis, Jc, Folsom, Ar, Benjamin, E, Aulchenko, Y, Haritunians, T, Couper, D, Murabito, J, Wang, Ya, Stricker, B, Gottdiener, J, Chang, Pp, Wang, Tj, Rice, Km, Heckbert, Sr, Fox, Er, Uitterlinden, Ag, Willerson, Jt, van Duijn, Cm, Witteman, Jc, Vasan, R, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Parsa, A, Gao, X, Yang, Q, Smith, Av, O'Connell, Jr, Schmidt, H, Tanaka, T, Isaacs, A, Ketkar, S, Hwang, Sj, Johnson, A, Teumer, A, Paré, G, Atkinson, Ej, Lohman, K, Cornelis, Mc, Probst-Hensch, Nm, Kronenberg, F, Tönjes, A, Hayward, C, Aspelund, T, Eiriksdottir, G, Launer, Lj, Harris, Tb, Rampersaud, E, Mitchell, Bd, Arking, De, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, Francesco, Metter, J, de Boer, J, Zillikens, Mc, Oostra, Ba, Feitosa, M, Province, M, de Andrade, M, Turne, St, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, T, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, A, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Liu, Y, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Prokopenko, I, Wang, W, Shuldiner, Ar, Coresh, J, Schmidt, R, Ferrucci, L, Shlipak, Mg, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, C, Felix, Sb, Watzinger, N, Larson, Mg, Homuth, G, Aragam, J, Dörr, M, Zweiker, R, Lind, L, Rodeheffer, Rj, Greiser, Kh, Deckers, Jw, Stritzke, J, Lackner, Kj, Ingelsson, E, Kullo, I, Haerting, J, Stricker, Bh, Reffelmann, T, Redfield, Mm, Werdan, K, Mitchell, Gf, Arnett, D, Blettner, M, Friedrich, N, Benjamin, Ej, Chambers, Jc, Zhang, W, Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, J, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Davey Smith, G, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, T, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, Homan van der Heide, Jj, Hepkema, Bg, Hernandez-Fuentes, M, Hypponen, E, Johnson, T, de Jong, Pe, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Munroe, Pb, Nordfors, L, Penninx, Bw, Perucha, E, Pouta, A, Roderick, Pj, Ruokonen, A, Sanna, S, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink-Veltmaat, Lj, Uda, M, Vollenweider, P, Wallace, C, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Abecasis, Gr, Lightstone, L, Scott, J, Navis, G, Elliot, P, and Kooner, Js.
Subjects: novel loci, Kidney Disease, Polymorphism, Single Nucleotide/*genetics, [SDV]Life Sciences [q-bio], left ventricular wall thickness, LOCI, Genome-wide association study, Blood Pressure, Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, RELEVANCE, Africa/ethnology, Cardiovascular Disease, genetics, Kidney Diseases/genetics, Stroke, genome wide association study, POPULATION, ta118, Blood pressure, hypertension, stroke, coronary artery disease, ddc:616, 0303 health sciences, education.field_of_study, Asia/ethnology, Multidisciplinary, Coronary Artery Disease/genetics, COMMON VARIANTS, Genetic Predisposition to Disease/*genetics, 3. Good health, Europe, Cardiovascular Diseases, Hypertension, Cardiology, Kidney Diseases, HEALTH, Human, medicine.medical_specialty, Asia, Population, Renal function, Polymorphism, Single Nucleotide, Europe/ethnology, Article, CLONING, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Stroke/genetics, Internal medicine, medicine, Humans, Cardiovascular Diseases/*genetics, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, METAANALYSIS, 030304 developmental biology, RECEPTOR, genes, blood pressure, cardiovascular disease risk, medicine.disease, Africa, Blood Pressure/*genetics/physiology, Hypertension/genetics, Kidney disease, Genome-Wide Association Study
Abstract: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. ispartof: Nature vol:478 issue:7367 pages:103-109 ispartof: location:England status: published
Published: 2011

12. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, Dmitry, Winkler, Thomas W, Workalemahu, Tsegaselassie, Hartman, Catharina A, Duncan, Emma L, Ntzani, Evangelia E, Oei, Ling, Albagha, Omar M E, Amin, Najaf, Kemp, John P, Koller, Daniel L, Li, Guo, Liu, Ching-Ti, Minster, Ryan L, Hassinen, Maija, Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su-Mei, Yerges-Armstrong, Laura M, Zheng, Hou-Feng, Alonso, Nerea, Eriksson, Joel, Kammerer, Candace M, Kaptoge, Stephen K, Hayward, Caroline, Leo, Paul J, Thorleifsson, Gudmar, Wilson, Scott G, Wilson, James F, Aalto, Ville, Alen, Markku, Aragaki, Aaron K, Aspelund, Thor, Center, Jacqueline R, Dailiana, Zoe, Heikkilä, Kauko, Duggan, David J, Garcia, Melissa, Garcia-Giralt, Natàlia, Giroux, Sylvie, Hallmans, Göran, Hocking, Lynne J, Husted, Lise Bjerre, Jameson, Karen A, Khusainova, Rita, Kim, Ghi Su, Herzig, Karl-Heinz, Kooperberg, Charles, Koromila, Theodora, Kruk, Marcin, Laaksonen, Marika, Lacroix, Andrea Z, Lee, Seung Hun, Leung, Ping C, Lewis, Joshua R, Masi, Laura, Mencej-Bedrac, Simona, Helmer, Quinta, Nguyen, Tuan V, Nogues, Xavier, Patel, Millan S, Prezelj, Janez, Rose, Lynda M, Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V, Svensson, Olle, Trompet, Stella, Hillege, Hans L, Trummer, Olivia, van Schoor, Natasja M, Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M, Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Holmen, Oddgeir, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Hunt, Steven C, Langdahl, Bente Lomholt, Leslie, William D, Lips, Paul, Ljunggren, Östen, Lorenc, Roman S, Marc, Janja, Mellström, Dan, Obermayer-Pietsch, Barbara, Olmos, José M, Pettersson-Kymmer, Ulrika, Isaacs, Aaron, Reid, David M, Riancho, José A, Ridker, Paul M, Rousseau, François, Slagboom, P Eline, Tang, Nelson L S, Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, María T, Wu, 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S, North, Kari E, Forouhi, Nita G, Edkins, Sarah, Varga, Tibor V, Oksa, Heikki, Antonella, Mulas, Moffatt, Miriam F, Kong, Augustine, Herder, Christian, Antti, Jula, Small, Kerrin, Miljkovic, Iva, Atalay, Mustafa, Kiess, Wieland, Murabito, Joanne M, Smit, Johannes H, Campbell, Susan, Fowkes, Gerard R, Nicholson, George, Kovacs, Peter, Zemunik, Tatijana, Basart, Hanneke V, Rathmann, Wolfgang, Maerz, Winfried, Peters, Annette, Province, Michael A, Hastie, Nicholas D, Olsson, Christian, Stumvoll, Michael, Waterworth, Dawn M, Watanabe, Richard M, de Geus, Eco J C, Penninx, Brenda W, Perry, John Rb, Reinmaa, Eva, Dedoussis, George V, Kutalik, Zoltán, Toenjes, Anke, Peyser, Patricia A, Körner, Antje, Keinanen-Kiukaanniemi, Sirkka M, Schadt, Eric E, Saaristo, Timo E, Dupuis, Josée, Sattar, Naveed, Cucca, Francesco, Balkau, Beverley, Froguel, Philippe, Jarvelin, Marjo-Riitta, Bouatia-Naji, Nabila, Stolk, Lisette, Meigs, James B, Ahmadi, Kourosh R, Ainali, Chrysanthi, Barrett, Amy, Vallejo, 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Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, W., Albrecht, E., Alizadeh, BZ., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Keyzer, J., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Department of Clinical Sciences, Lund University [Lund], Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Umeå University, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, Limnology, Ecology, Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Institute of Medical Informatics, Biometry and Epidemiology, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Space Sciences Laboratory [Berkeley] (SSL), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, King‘s College London, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Department of Pharmacy Sciences, Creighton University Medical Center, Medical Department III, Universität Leipzig, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Epidemiology, Erasmus Medical Centre, Netherlands Genomics Initiative (NGI), Netherlands Genomics Initiative, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Public Health and Clinical Medicine, Medstar Research Institute, Genetics and Pathology, Finnish Institute of Occupational Health, Epidemiology, University Medical Centre Groningen, Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, University of California [Irvine] (UC Irvine), Department of Odontology, Cariology, Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Division of Cardiology, Geneva University Hospital (HUG), Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Anaesthesia and Intensive care, Royal Aberdeen Childrens Hospital, UCL Institute of neurology, UCL Institute of Neurology, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Departments of Epidemiology and Nutrition, Harvard School of Public Health, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Department of Genetics, University of Groningen [Groningen], deCODE Genetics, deCODE genetics [Reykjavik], Pediatric Pulmonology, Allergology & Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Department of Nutrition-Dietetics, Harokopio University of Athens, Yale School of Medicine [New Haven, Connecticut] (YSM), National Heart and Lung Institute (NHLI), Imperial College London, Queensland Institute of Medical Research, Concord Hospital, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Dept. 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Greifswald - University of Greifswald, Interfaculty Institute for Genetics and Functional Genomics, 5 University Street, Centre for Paediatric Epidemiology and Biostatistics, University College of London [London] (UCL), MRC Centre for Epidemiology of Child Health, UCL Institute of Child Health, Unit for Molecular Epidemiology, Institute of Health Sciences and Biocenter Oulu, University of Oulu, Department of Epidemiology and Biostatistics, Department of Life Course and Services, National Institute for Health and Welfare [Helsinki], Department of Epidemiology and Public Health, Queen's University [Belfast] (QUB), Interdisciplinary Center of Clinical Research, Department of Physiology, University of Eastern Finland-Institute of Biomedicine, University of Hawai‘i [Mānoa] (UHM), Department of Clinical Chemistry, University of Tampere [Finland]-Tampere University Hospital, Chronic Disease Epidemiology and Prevention Unit, Université Laval [Québec] (ULaval), Centre for Bone and Arthritis 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= University of Helsinki, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, MRC epidemiology Unit, Institute of Epidemiology, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Oncology, Queensland Brain Institute, University of Queensland [Brisbane], Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Massachusetts General Hospital [Boston], Divisions of Genetics and Endocrinology and Program in Genomics, Boston Children's Hospital, Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Metabolic Disease Group, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Epidemiology Unit, Addenbrooke's Hospital-Medical Research Council (MRC), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Landsteiner Laboratory, Clinical Haematology, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Lund University Diabetes Centre-Lund University [Lund], Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Technical University of Denmark [Lyngby] (DTU), Université de Lausanne (UNIL), Universität Duisburg-Essen [Essen], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California [Berkeley], University of California-University of California, Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of California [Irvine] (UCI), German Research Center for Environmental Health, University of Bonn, Czech Academy of Sciences [Prague] (ASCR), Yale University School of Medicine, University of Oxford [Oxford], German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Laval University, Laval University [Québec], Turku University Hospital, Lausanne university hospital, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Helmholtz-Zentrum München (HZM), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Internal Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Medical Informatics, Obstetrics & Gynecology, Lund University [Lund]-Lund University Diabetes Centre, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institute of Medicine-University of Gothenburg (GU), Signalisation et Transports Ioniques Membranaires ( STIM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Technical University of Denmark [Lyngby] ( DTU ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Department of Medical Epidemiology and Biostatistics ( MEB ), University of Lausanne, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC, Space Sciences Laboratory [Berkeley] ( SSL ), Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), University of Leipzig, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Epidemiology [Neuherberg] ( EPI ), University of California [Irvine] ( UCI ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Geneva University Hospital ( HUG ), Bonn Universität [Bonn], Indian Institute of Technology Kanpur ( IIT Kanpur ), The University of North Carolina at Chapel Hill, Université de Bonn, Wellcome Trust Sanger Institute, Harvard University School of Public Health, Czech Academy of Sciences [Prague] ( ASCR ), deCODE genetics, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Yale School of Medicine, National Heart and Lung Institute ( NHLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, University Medical Center Groningen, University of Cambridge [UK] ( CAM ), Wellcome Trust Centre for Human Genetics, University of Pisa [Pisa], University of Cambridge [UK] ( CAM ) -Institute of Metabolic Science, German Research Center for Environmental Health-Helmholtz-Zentrum München ( HZM ), University of Otago, University of Greifswald, University College of London [London] ( UCL ), National Institute for Health and Welfare, Queen's University [Belfast] ( QUB ), University of Hawaii at Manoa ( UHM ), University of Gothenburg ( GU ) -Institute of Medicine, Recherches en Psychopathologie, nouveaux symptômes et lien social ( EA 4050 ), Université de Poitiers-Université de Brest ( UBO ) -Université Catholique de l'Ouest-Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Finland Institute for Molecular Medicine ( FIMM ), Georgia Prevention Institute, Netherlands Consortium for Healthy Aging, Helmholtz-Zentrum München ( HZM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Massachusetts General Hospital, Children's Hospital, Boston, Broad Institute, Cambridge, MA, The University of North Carolina at Chapel Hill-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Shungin D, Winkler TW, Adipogen, Consortium, Cardiogramplusc4d, Consortium, Ckdgen, Consortium, Gefos, Consortium, Genie, Consortium, Glgc, Icbp, International, Endogene Consortium, Lifelines, Cohort Study, Magic, Investigator, Muther, Consortium, Consortium, Page, ReproGen Consortium, Amouyel P, D'Adamo, ADAMO PIO, Gasparini, Paolo, Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Hypponen, Elina, Mohlke, Karen L, ADIPOGEN Consortium, Int Endogene Consortium, Lee Kong Chian School of Medicine (LKCMedicine), Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, Cooper, R, Dedoussis, G, Ferrucci, L, Froguel, P, Grabe, H, Hamsten, A, Hui, J, Hveem, K, Jöckel, K, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, März, W, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Pe'Russe, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sinisalo, J, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Van Der Harst, P, Veronesi, G, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Abecasis, G, Assimes, T, Berndt, S, Boehnke, M, Borecki, I, Deloukas, P, Franke, L, Frayling, T, Groop, L, Hunter, D, Kaplan, R, O'Connell, J, Qi, L, Schlessinger, D, Strachan, D, Stefansson, K, Van Duijn, C, Willer, C, Visscher, P, Yang, J, Hirschhorn, J, Zillikens, M, Mccarthy, M, Speliotes, E, North, K, Fox, C, Barroso, I, Franks, P, Ingelsson, E, Heid, I, Loos, R, Cupples, L, Lindgren, C, Mohlke, K, Dastani, Z, Timpson, N, Yuan, X, Henneman, P, Kizer, J, Lyytikainen, L, Fuchsberger, C, Small, K, Coassin, S, Lohman, K, Pankow, J, Uh, H, Wu, Y, Bidulescu, A, Rasmussen Torvik, L, Greenwood, C, Ladouceur, M, Grimsby, J, Manning, A, Mooser, V, Kapur, K, Frants, R, Willemsvan vanDijk, K, Willems, S, Psaty, B, Tracy, R, Brody, J, Chen, I, Viikari, J, Kähönen, M, Evans, D, St Pourcain, B, Sattar, N, Carlson, O, Egan, J, van Heemst, D, Kedenko, L, Nuotio, M, Loo, B, Kanaya, A, Haun, M, Klopp, N, Katsareli, E, Couper, D, Duncan, B, Kloppenburg, M, Borja, J, Musani, S, Guo, X, Semple, R, Teslovich, T, Allison, M, Redline, S, Buxbaum, S, Meulenbelt, I, Ballantyne, C, Hu, F, Paulweber, B, Florez, J, Smith, G, Siscovick, D, Kronenberg, F, van Duijn, C, Waterworth, D, Meigs, J, Dupuis, J, Richards, J, Willenborg, C, Thompson, J, Erdmann, J, Goldstein, B, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikäinen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Cox, D, Dimitriou, M, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Peden, J, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Basart, H, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Goodall, A, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kim, H, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Hovingh, G, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Kathiresan, S, Roberts, R, Schunkert, H, Pattaro, C, Köttgen, A, Garnaas, M, Böger, C, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Döring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Wright, A, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Völzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Krämer, B, Portas, L, Ford, I, Buckley, B, Adam, M, Thun, G, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Gasparini, P, Pirastu, M, Jukema, J, Probst Hensch, N, Toniolo, D, Coresh, J, Schmidt, R, Kardia, S, Curhan, G, Gyllensten, U, Franke, A, Rettig, R, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, van der Harst, P, Arking, D, Franceschini, N, Hernandez, D, Townsend, R, Lumley, T, Kestenbaum, B, Haritunians, T, Waeber, G, Lu, X, Leak, T, Aasarød, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Beckmann, J, Dreisbach, A, Styrkarsdottir, U, Evangelou, E, Hsu, Y, Duncan, E, Ntzani, E, Oei, L, Albagha, O, Kemp, J, Koller, D, Minster, R, Vandenput, L, Willner, D, Xiao, S, Yerges Armstrong, L, Zheng, H, Alonso, N, Kammerer, C, Kaptoge, S, Leo, P, Wilson, S, Aalto, V, Alen, M, Aragaki, A, Center, J, Dailiana, Z, Duggan, D, Garcia Giralt, N, Giroux, S, Hocking, L, Husted, L, Jameson, K, Khusainova, R, Kim, G, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, A, Lee, S, Leung, P, Lewis, J, Masi, L, Mencej Bedrac, S, Nguyen, T, Nogues, X, Patel, M, Prezelj, J, Scollen, S, Siggeirsdottir, K, Svensson, O, Trummer, O, van Schoor, N, Woo, J, Zhu, K, Balcells, S, Brandi, M, Cheng, S, Christiansen, C, Cooper, C, Frost, M, Goltzman, D, González Macías, J, Karlsson, M, Khusnutdinova, E, Koh, J, Kollia, P, Langdahl, B, Leslie, W, Lips, P, Ljunggren, Ö, Lorenc, R, Marc, J, Mellström, D, Obermayer Pietsch, B, Olmos, J, Pettersson Kymmer, U, Reid, D, Riancho, J, Rousseau, F, Tang, N, Urreizti, R, Van Hul, W, Zarrabeitia, M, Castano Betancourt, M, Herrera, L, Ingvarsson, T, Johannsdottir, H, Kwan, T, Li, R, Luben, R, Medina Gómez, C, Palsson, S, Reppe, S, Sigurdsson, G, van Meurs, J, Verlaan, D, Williams, F, Zhou, Y, Gautvik, K, Raychaudhuri, S, Cauley, J, Clark, G, Cummings, S, Danoy, P, Dennison, E, Eastell, R, Eisman, J, Jackson, R, Jones, G, Khaw, K, Mccloskey, E, Nandakumar, K, Peacock, M, Pols, H, Prince, R, Reid, I, Robbins, J, Sambrook, P, Sham, P, Tylavsky, F, Econs, M, Kung, A, Reeve, J, Streeten, E, Karasik, D, Ralston, S, Ioannidis, J, Kiel, D, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Mäkinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkilä, O, Hietala, K, Kytö, J, Lahermo, P, Lehto, M, Österholm, A, Parkkonen, M, Pitkäniemi, J, Rosengård Bärlund, M, Saraheimo, M, Sarti, C, Söderlund, J, Soro Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Wadén, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Tregouet, D, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Möllsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Fraser, R, Freitag, D, Gurdasani, D, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Van den Herik, E, Volcik, K, Asiki, G, Been, L, Bolton, J, Bonnycastle, L, Burnett, M, Cesana, G, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, 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Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Würtz, P, Ong, R, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Dominiczak, A, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Anderson, C, Gordon, S, Guo, Q, Henders, A, Lambert, A, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Alizadeh, B, de Boer, R, Boezen, H, van der Klauw, M, Ormel, J, Postma, D, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Lecoeur, C, Johnson, P, Hottenga, J, Salo, P, Bielak, L, Zhao, W, Horikoshi, M, Navarro, P, Chen, H, Rybin, D, Song, K, An, P, Marullo, L, Jansen, H, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Toenjes, A, Peyser, P, Körner, A, Cucca, F, Balkau, B, Bouatia Naji, N, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Hedman, Å, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Higashio, J, Williams, R, Nato, A, Ambite, J, Manolio, T, Hindorff, L, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown Gentry, K, Thornton Wells, T, Dumitrescu, L, Jeff, J, Bush, W, Mitchell, S, Goodloe, R, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Zheng, W, Spencer, K, Pendergrass, S, Wilkens, L, Park, L, Tiirikainen, M, Kolonel, L, Lim, U, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Schumacher, F, Anderson, G, Carlson, C, Prentice, R, Wu, C, Carty, C, Gong, J, Rosse, S, Young, A, Haessler, J, Kocarnik, J, Lin, Y, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chanock, S, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hall, P, Hankinson, S, Hass, M, Heath, A, Janssens, A, Keyzer, J, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Medland, S, Melzer, D, Newman, A, Paré, G, Peeters, P, Pop, V, Räikkönen, K, Salumets, A, 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Subjects: Adipose Tissue/metabolism, Male, genetic association, subcutaneous fat, Transcription, Genetic, Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Mass Index, Continental Population Groups, Epigenesis, Genetic, Europe, Female, Genome, Human, Humans, Insulin, Insulin Resistance, Models, Biological, Neovascularization, Physiologic, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Characteristics, Waist-Hip Ratio, Body Fat Distribution, Genome-Wide Association Study, Multidisciplinary, Insulin Resistance/genetics, Genome-wide association study, Continental Population Groups/genetics, genetic analysis, heritability, gene cluster, Science::Biological sciences::Human anatomy and physiology [DRNTU], 0302 clinical medicine, high density lipoprotein cholesterol, Models, genetics [Insulin Resistance], histone modification, Age Factor, insulin receptor, 0303 health sciences, Adipocyte, Human/genetics, CARDIOGRAMplusC4D Consortium, ADIPOGENIC DIFFERENTIATION, genetic correlation, body fat, Continental Population Group, priority journal, 5 trisphosphate 3 phosphatase, GEFOS Consortium, meta analysis (topic), Science & Technology - Other Topics, ddc:500, transcription regulation, Adipogenesis/genetics, Single Nucleotide/genetics, Human, medicine.medical_specialty, Waist, phosphatidylinositol 3, European, ta3111, genetic regulation, Article, developmental biology, 03 medical and health sciences, MAGIC Investigators, transcription initiation site, SDG 3 - Good Health and Well-being, Genetic, genomics, GLYCEMIC TRAITS, genetics [Continental Population Groups], Polymorphism, GENOME-WIDE ASSOCIATION, Physiologic, genetics [Adipogenesis], Adipocytes/metabolism, Europe/ethnology, Genome, Human/genetics, Insulin/metabolism, Neovascularization, Physiologic/genetics, Obesity/genetics, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Transcription, Genetic/genetics, Genetic/genetics, Adipogenesi, Science & Technology, adiponectin, [ SDV ] Life Sciences [q-bio], vasculotropin, genetics [Quantitative Trait Loci], ta1184, Racial Groups, ta1182, gene mapping, ta3121, triacylglycerol blood level, medicine.disease, Biological, major clinical study, amino acid sequence, metabolism [Insulin], Endocrinology, metabolism [Adipocytes], genetic loci, insulin, body fat, GLGC, International Endogene Consortium, metabolism [Adipose Tissue], Body mass index, HUMAN HEIGHT, Epigenesis, LifeLines Cohort Study, ReproGen Consortium, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, tissue level, Physiologic/genetics, [SDV]Life Sciences [q-bio], Medizin, Adipose tissue, low density lipoprotein cholesterol, PAGE Consortium, COMMON SNPS, angiogenesis, Waist–hip ratio, genetics [Obesity], MESH: Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, single nucleotide polymorphism, fat, genetic variability, molecular biology, body mass index (BMI), ethnology [Europe], peroxisome proliferator activated receptor, 2. Zero hunger, Genetics, Genome, Single Nucleotide, waist circumference, insulin, phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase, triacylglycerol, vasculotropin, developmental biology, gene expression, genome, numerical model, adipocyte, adipose tissue, body fat distribution, body mass, female, gene locus, gene structure, hip circumference, human, insulin resistance, lipoprotein blood level, male, obesity, protein protein interaction, sex difference, waist hip ratio, Multidisciplinary Sciences, genetics [Transcription, Genetic], genetics [Polymorphism, Single Nucleotide], ADIPOGen Consortium, genetics [Neovascularization, Physiologic], Transcription, SUSCEPTIBILITY LOCI, General Science & Technology, ICBP, 030209 endocrinology & metabolism, Biology, adipocyte, MESH : Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, MESENCHYMAL STEM-CELLS, GENIE Consortium, SEXUAL-DIMORPHISM, Insulin resistance, Internal medicine, medicine, genetics [Genome, Human], ABDOMINAL ADIPOSITY, Neovascularization, 030304 developmental biology, FALSE DISCOVERY, CKDGen Consortium, Sex Characteristic, MuTHER Consortium, numerical model
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P
Published: 2015

13. Genetic studies of body mass index yield new insights for obesity biology

Author: Locke, Adam E, Kahali, Bratati, Croteau-Chonka, Damien C, Doney, Alex S F, He, Bing, Heikkilä, Outi, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Eklund, Niina, Saraheimo, Markku, Sarti, Cinzia, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Estrada, Karol, Wadén, Johan, Gill, Geoffrey V, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Eury, Elodie, Ladenvall, Claes, Alhenc-Gelas, François, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Folkersen, Lasse, Möllsten, Anna, Cimponeriu, Dan, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Fraser, Ross M, Colhoun, Helen M, Panduru, Nicolae Mircea, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Garcia, Melissa E, Waggott, Daryl, Paterson, Andrew D, Savage, David A, Bain, Stephen C, Martin, Finian, Hirschhorn, Joel N, Godson, Catherine, Florez, Jose C, Groop, Per-Henrik, Maxwell, Alexander P, Geller, Frank, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L, Mora, Samia, Giedraitis, Vilmantas, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Chang, Hsing-Y, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Gigante, Bruna, Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Freitag, Daniel F, Gurdasani, Deepti, Heikkilä, Kauko, Hyppönen, Elina, Isaacs, Aaron, Jackson, Anne U, Esko, Tonu, Go, Alan S, Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Golay, Alain, Mihailov, Evelin, Montasser, May E, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Goodall, Alison H, Service, Susan K, Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Thorleifsson, Gudmar, Gordon, Scott D, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Gorski, Mathias, Been, Latonya F, Bolton, Jennifer L, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doring, Angela, Elliott, Paul, Grabe, Hans-Jörgen, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hallmans, Göran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John J P, Khaw, Kay-Tee, Kim, Eric, Grammer, Tanja B, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimaki, Terho, Lin, Shih-Yi, Lindstrom, Jaana, Loos, Ruth J F, Mach, François, McArdle, Wendy L, Gräßler, Jürgen, Meisinger, Christa, Mitchell, Braxton D, Muller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V M, Nsubuga, Rebecca N, Olafsson, Isleifur, Ong, Ken K, Palotie, Aarno, Grönberg, Henrik, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J, Reilly, Muredach P, Ridker, Paul M, Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Fall, Tove, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stančáková, Alena, Stirrups, Kathleen, Swift, Amy J, Tiret, Laurence, Uitterlinden, Andre G, van Pelt, L Joost, Vedantam, Sailaja, Gusto, Gaëlle, Wainwright, Nicholas, Wijmenga, Cisca, Wild, Sarah H, Willemsen, Gonneke, Wilsgaard, Tom, Wilson, James F, Young, Elizabeth H, Zhao, Jing Hua, Adair, Linda S, Arveiler, Dominique, Haessler, Jeffrey, Assimes, Themistocles L, Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O, Boomsma, Dorret I, Borecki, Ingrid B, Bornstein, Stefan R, Bovet, Pascal, Burnier, Michel, Hall, Per, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chen, Yii-Der Ida, Collins, Francis S, Cooper, Richard S, Danesh, John, Dedoussis, George, de Faire, Ulf, Feranil, Alan B, Haller, Toomas, Ferrieres, Jean, Ferrucci, Luigi, Freimer, Nelson B, Gieger, Christian, Groop, Leif C, Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Hingorani, Aroon, Hallmans, Goran, Hofman, Albert, Hovingh, G Kees, Hsiung, Chao Agnes, Humphries, Steve E, Hunt, Steven C, Hveem, Kristian, 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Harris, T, Hattersley, A, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Homuth, G, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Illig, T, Jacobs, K, Jarvelin, M, Jockel, K, Johansen, B, Jousilahti, P, Jukema, J, Jula, A, Kaprio, J, Kastelein, J, Keinanen-Kiukaanniemi, S, Kiemeney, L, Knekt, P, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Marchand, L, Lehtimaki, T, Lyssenko, V, Mannisto, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Moll, F, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Madden, P, Pasterkamp, G, Peden, J, Peters, A, Postma, D, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Rioux, J, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schunkert, H, Schwarz, P, Sever, P, Shuldiner, A, Sinisalo, J, Stolk, R, Strauch, K, Tonjes, A, Tregouet, D, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Volker, U, Waeber, G, Willemsen, G, 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A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Freitag, D, Gurdasani, D, Heikkila, K, Johnson, T, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Teslovich, T, Van den Herik, E, Volcik, K, Wu, Y, Asiki, G, Been, L, Burnett, M, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Khaw, K, Kim, E, Komulainen, P, Lin, S, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Young, E, Bennett, F, Boomsma, D, Burnier, M, Feranil, A, Freimer, N, Hsiung, C, Kesaniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Meneton, P, Moilanen, L, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton-Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sober, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjogren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland-Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Brown, M, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Staessen, J, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Smith, G, Raffel, L, Yao, J, Schwartz, S, Ikram, M, W, L, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace-Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Wurtz, P, Ong, R, Dorr, M, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Guo, X, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, Palmer, L, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Alizadeh, B, de Boer, R, Boezen, H, Hillege, H, van der Klauw, M, 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J, Ramos, R, Williams, G, Nathan, D, Macrae, C, Berglund, G, Asselta, R, Duga, S, Spreafico, M, Daly, M, Nemesh, J, Korn, J, Surti, A, Gianniny, L, Parkin, M, Burtt, N, Gabriel, S, Wright, B, Ball, S, Schunkert, I, Linsel-Nitschke, P, Lieb, W, Fischer, M, Grosshennig, A, Preuss, M, Scholz, M, Chen, Z, Wilensky, R, Matthai, W, Qasim, A, Hakonarson, H, Devaney, J, Pichard, A, Kent, K, Satler, L, Lindsay, J, Waksman, R, Knouff, C, Scheffold, T, Berger, K, Huge, A, Martinelli, N, Olivieri, O, Corrocher, R, Xie, C, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, Di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Yang, T, Higashio, J, Williams, R, Nato, A, Ambite, J, Deelman, E, Manolio, T, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown-Gentry, K, Thornton-Wells, T, Dumitrescu, L, Bush, W, Mitchell, S, Goodloe, R, Wilson, S, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Spencer, K, Pendergrass, S, Le Marchand, L, Park, L, Tiirikainen, M, Kolonel, L, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Anderson, G, Carlson, C, Prentice, R, Lacroix, A, Wu, C, Carty, C, Rosse, S, Young, A, Kocarnik, J, Lin, Y, Jackson, R, Duggan, D, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hankinson, S, Hass, M, Janssens, A, Karasik, D, Keyzer, J, Kiel, D, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Melzer, D, Newman, A, Pare, G, Peeters, P, Pop, V, Raikkonen, K, Salumets, A, Stacey, S, Starr, J, Stathopoulou, M, Styrkarsdottir, U, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Widen, E, Wijnands-Van Gent, C, Yerges-Armstrong, L, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Streeten, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Koller, D, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Couper, D, Easton, D, Foroud, T, Kilpelainen, T, Li, S, Murray, S, Ness, A, Northstone, K, Peacock, M, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segre, A, Sovio, U, Srinivasan, S, Tammesoo, M, van Meurs, J, Young, L, Bierut, L, Econs, M, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International Endogene Consortium, Berndt, Sonja I, Justice, Anne E, Hyppönen, Elina Tuulikki, Epidemiology and Data Science, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
Subjects: Male, LOCI, Genome-wide association study, Continental Population Groups/genetics, VARIANTS, Body Mass Index, Insulin Secretion, Insulin, Age Factor, Adiposity, ddc:616, Adipogenesis, Genetic Predisposition to Disease/genetics, Synapse, 3. Good health, Continental Population Group, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], GENOME-WIDE ASSOCIATIONPROVIDES INSIGHTSGLYCEMIC TRAITSLOCIMETAANALYSISVARIANTSINDIVIDUALSHIPPOCAMPALARCHITECTURETOPIRAMATE, ddc:500, Adipogenesis/genetics, Single Nucleotide/genetics, Age Factors, Continental Population Groups, Energy Metabolism, Europe, Female, Genetic Predisposition to Disease, Glutamic Acid, Humans, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses, Genome-Wide Association Study, Multidisciplinary, genetics [Adiposity], Human, Socio-culturale, genetics [Energy Metabolism], ta3111, genetic, body mass index, obesity, SDG 3 - Good Health and Well-being, GLYCEMIC TRAITS, genetics [Continental Population Groups], Genetic variability, Polymorphism, GENOME-WIDE ASSOCIATION, genetics [Adipogenesis], METAANALYSIS, Genetic association, Adipogenesi, genetics [Quantitative Trait Loci], ta1184, metabolism [Glutamic Acid], ta1182, PATHWAYS, metabolism [Synapses], ta3121, medicine.disease, metabolism [Insulin], Adiposity/genetics, Clinical Medicine, Quantitative Trait Loci/genetics, Body mass index, HUMAN HEIGHT, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Synapses/metabolism, Medizin, Obesity/genetics, Bioinformatics, genetic basis, Obesity/metabolism, genetics [Obesity], body mass index (BMI), genetics [Genetic Predisposition to Disease], ethnology [Europe], 2. Zero hunger, Genetics, ARCHITECTURE, Genetics of obesity, Medicine (all), Single Nucleotide, Polymorphism, Single Nucleotide/genetics, Insulin/metabolism/secretion, Glutamic Acid/metabolism, genetics [Polymorphism, Single Nucleotide], EXPRESSION, Insulin/metabolism, PROVIDES INSIGHTS, genetics [Racial Groups], Biology, Obesity/genetics/metabolism, Europe/ethnology, metabolism [Obesity], Mendelian randomization, medicine, Energy Metabolism/genetics, body mass, genetic analysis, obesity, Klinisk medicin
Abstract: Item does not contain fulltext Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
Published: 2015

14. A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans

Author: Palmer, Nicholette D, McDonough, Caitrin W, Hicks, Pamela J, Roh, Bong H, Wing, Maria R, An, S Sandy, Hester, Jessica M, Cooke, Jessica N, Bostrom, Meredith A, Rudock, Megan E, Talbert, Matthew E, Lewis, Joshua P, DIAGRAM Consortium, MAGIC Investigators, Ferrara, Assiamira, Lu, Lingyi, Ziegler, Julie T, Sale, Michele M, Divers, Jasmin, Shriner, Daniel, Adeyemo, Adebowale, Rotimi, Charles N, Ng, Maggie CY, Langefeld, Carl D, Freedman, Barry I, Bowden, Donald W, Voight, Benjamin F, Scott, Laura J, Steinthorsdottir, Valgerdur, Morris, Andrew P, Dina, Christian, Welch, Ryan P, Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S, Thorleifsson, Gudmar, McCulloch, Laura J, Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J, Raychaudhuri, Soumya, McCarroll, Steve A, Langenberg, Claudia, Hofmann, Oliver M, Dupuis, Josée, Qi, Lu, Segrè, Ayellet V, Van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Benediktsson, Rafn, Bennett, Amanda J, Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L, Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P, Charpentier, Guillaume, Chines, Peter S, Cornelis, Marilyn, Couper, David J, Crawford, Gabe, Doney, Alex SF, Elliott, Katherine S, Elliott, Amanda L, Erdos, Michael R, Fox, Caroline S, Franklin, Christopher S, Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J, Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U, Johnson, Paul RV, Jørgensen, Torben, Kao, Wen HL, Klopp, Norman, Kong, Augustine, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Aloysius, Lindgren, Cecilia M, Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, Midthjell, Kristian, Morken, Mario A, Narisu, Narisu, Nilsson, Peter, Owen, Katharine R, Payne, Felicity, Perry, John RB, Petersen, Ann-Kristin, Platou, Carl, Proença, Christine, Prokopenko, Inga, Rathmann, Wolfgang, Rayner, N William, Robertson, Neil R, Rocheleau, Ghislain, Roden, Michael, Sampson, Michael J, Saxena, Richa, Shields, Beverley M, Shrader, Peter, Sigurdsson, Gunnar, Sparsø, Thomas, Strassburger, Klaus, Stringham, Heather M, Sun, Qi, Swift, Amy J, Thorand, Barbara, Tichet, Jean, Tuomi, Tiinamaija, Van Dam, Rob M, Van Haeften, Timon W, Van Herpt, Thijs, Van Vliet-Ostaptchouk, Jana V, Walters, G Bragi, Weedon, Michael N, Wijmenga, Cisca, Witteman, Jacqueline, Bergman, Richard N, Cauchi, Stephane, Collins, Francis S, Gloyn, Anna L, Gyllensten, Ulf, Hansen, Torben, Hide, Winston A, Hitman, Graham A, Hofman, Albert, Hunter, David J, Hveem, Kristian, Laakso, Markku, Mohlke, Karen L, Morris, Andrew D, Palmer, Colin NA, Pramstaller, Peter P, Rudan, Igor, Sijbrands, Eric, Stein, Lincoln D, Tuomilehto, Jaakko, Uitterlinden, Andre, Walker, Mark, Wareham, Nicholas J, Watanabe, Richard M, Abecasis, Goncalo R, Boehm, Bernhard O, Campbell, Harry, Daly, Mark J, Hattersley, Andrew T, Hu, Frank B, Meigs, James B, Pankow, James S, Pedersen, Oluf, Wichmann, H-Erich, Barroso, Inês, Florez, Jose C, Frayling, Timothy M, Groop, Leif, Sladek, Rob, Thorsteinsdottir, Unnur, Wilson, James F, Illig, Thomas, Froguel, Philippe, Van Duijn, Cornelia M, Stefansson, Kari, Altshuler, David, Boehnke, Michael, McCarthy, Mark I, Soranzo, Nicole, Wheeler, Eleanor, Glazer, Nicole L, Bouatia-Naji, Nabila, Mägi, Reedik, Randall, Joshua, Johnson, Toby, Elliott, Paul, Rybin, Denis, Henneman, Peter, Dehghan, Abbas, Hottenga, Jouke Jan, Song, Kijoung, Goel, Anuj, Egan, Josephine M, Lajunen, Taina, Doney, Alex, Kanoni, Stavroula, Cavalcanti-Proença, Christine, Kumari, Meena, Timpson, Nicholas J, Zabena, Carina, Ingelsson, Erik, An, Ping, O'Connell, Jeffrey, Luan, Jian'an, Elliott, Amanda, McCarroll, Steven A, Roccasecca, Rosa Maria, Pattou, François, Sethupathy, Praveen, Ariyurek, Yavuz, Barter, Philip, Beilby, John P, Ben-Shlomo, Yoav, Bergmann, Sven, Bochud, Murielle, Bonnefond, Amélie, Borch-Johnsen, Knut, Böttcher, Yvonne, Brunner, Eric, Bumpstead, Suzannah J, Chen, Yii-Der Ida, Chines, Peter, Clarke, Robert, Coin, Lachlan JM, Cooper, Matthew N, Crisponi, Laura, Day, Ian NM, De Geus, Eco JC, Delplanque, Jerome, Fedson, Annette C, Fischer-Rosinsky, Antje, Forouhi, Nita G, Frants, Rune, Franzosi, Maria Grazia, Galan, Pilar, Goodarzi, Mark O, Graessler, Jürgen, Grundy, Scott, Gwilliam, Rhian, Hallmans, Göran, Hammond, Naomi, Han, Xijing, Hartikainen, Anna-Liisa, Hayward, Caroline, Heath, Simon C, Hercberg, Serge, Hicks, Andrew A, Hillman, David R, Hingorani, Aroon D, Hui, Jennie, Hung, Joe, Jula, Antti, Kaakinen, Marika, Kaprio, Jaakko, Kesaniemi, Y Antero, Kivimaki, Mika, Knight, Beatrice, Koskinen, Seppo, Kovacs, Peter, Kyvik, Kirsten Ohm, Lathrop, G Mark, Lawlor, Debbie A, Le Bacquer, Olivier, Lecoeur, Cécile, Li, Yun, Mahley, Robert, Mangino, Massimo, Manning, Alisa K, Martínez-Larrad, María Teresa, McAteer, Jarred B, McPherson, Ruth, Meisinger, Christa, Melzer, David, Meyre, David, Mitchell, Braxton D, Mukherjee, Sutapa, Naitza, Silvia, Neville, Matthew J, Oostra, Ben A, Orrù, Marco, Pakyz, Ruth, Paolisso, Giuseppe, Pattaro, Cristian, Pearson, Daniel, Peden, John F, Pedersen, Nancy L, Perola, Markus, Pfeiffer, Andreas FH, Pichler, Irene, Polasek, Ozren, Posthuma, Danielle, Potter, Simon C, Pouta, Anneli, Province, Michael A, Psaty, Bruce M, Rayner, Nigel W, Rice, Kenneth, Ripatti, Samuli, Rivadeneira, Fernando, Rolandsson, Olov, Sandbaek, Annelli, Sandhu, Manjinder, Sanna, Serena, Sayer, Avan Aihie, Scheet, Paul, Seedorf, Udo, Sharp, Stephen J, Shields, Beverley, Sijbrands, Eric JG, Silveira, Angela, Simpson, Laila, Singleton, Andrew, Smith, Nicholas L, Sovio, Ulla, Swift, Amy, Syddall, Holly, Syvänen, Ann-Christine, Tanaka, Toshiko, Tönjes, Anke, Uitterlinden, André G, Van Dijk, Ko Willems, Varma, Dhiraj, Visvikis-Siest, Sophie, Vitart, Veronique, Vogelzangs, Nicole, Waeber, Gérard, Wagner, Peter J, Walley, Andrew, Ward, Kim L, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Witteman, Jaqueline CM, Yarnell, John WG, Zelenika, Diana, Zethelius, Björn, Zhai, Guangju, Zhao, Jing Hua, Zillikens, M Carola, Borecki, Ingrid B, Loos, Ruth JF, Meneton, Pierre, Magnusson, Patrik KE, Nathan, David M, Williams, Gordon H, Silander, Kaisa, Salomaa, Veikko, Smith, George Davey, Bornstein, Stefan R, Schwarz, Peter, Spranger, Joachim, Karpe, Fredrik, Shuldiner, Alan R, Cooper, Cyrus, Dedoussis, George V, Serrano-Ríos, Manuel, Lind, Lars, Palmer, Lyle J, Franks, Paul W, Ebrahim, Shah, Marmot, Michael, Kao, WH Linda, Pramstaller, Peter Paul, Wright, Alan F, Stumvoll, Michael, Hamsten, Anders, Buchanan, Thomas A, Valle, Timo T, Rotter, Jerome I, Siscovick, David S, Penninx, Brenda WJH, Boomsma, Dorret I, Deloukas, Panos, Spector, Timothy D, Ferrucci, Luigi, Cao, Antonio, Scuteri, Angelo, Schlessinger, David, Uda, Manuela, Ruokonen, Aimo, Jarvelin, Marjo-Riitta, Waterworth, Dawn M, Vollenweider, Peter, Peltonen, Leena, Mooser, Vincent, Sladek, Robert, Center for Liver, Digestive and Metabolic Diseases (CLDM), Palmer, Nd, Mcdonough, Cw, Hicks, Pj, Roh, Bh, Wing, Mr, An, S, Hester, Jm, Cooke, Jn, Bostrom, Ma, Rudock, Me, Talbert, Me, Lewis, Jp, Diagram, Consortium, Magic, Investigator, Ferrara, A, Lu, L, Ziegler, Jt, Sale, Mm, Divers, J, Shriner, D, Adeyemo, A, Rotimi, Cn, Ng, Mc, Langefeld, Cd, Freedman, Bi, Bowden, Dw, Voight, Bf, Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Couper, Dj, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, J, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Johnson, T, Elliott, P, Rybin, D, Henneman, P, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Egan, Jm, Lajunen, T, Kanoni, S, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Frants, R, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hicks, Aa, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Manning, Ak, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Oostra, Ba, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Perola, M, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Psaty, Bm, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tanaka, T, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Borecki, Ib, Loos, Rj, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Salomaa, V, Smith, Gd, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Dedoussis, Gv, Serrano Ríos, M, Lind, L, Palmer, Lj, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Buchanan, Ta, Valle, Tt, Rotter, Ji, Siscovick, D, Penninx, Bw, Boomsma, Di, Deloukas, P, Spector, Td, Ferrucci, L, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Waterworth, Dm, Vollenweider, P, Peltonen, L, Mooser, V, Sladek, R., Medical Research Council (MRC), Human genetics, Psychiatry, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, Langenberg, Claudia [0000-0002-5017-7344], Griffin, Simon [0000-0002-2157-4797], Wareham, Nicholas [0000-0003-1422-2993], Soranzo, Nicole [0000-0003-1095-3852], Wheeler, Eleanor [0000-0002-8616-6444], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Apollo - University of Cambridge Repository, DIAGRAM Consortium, MAGIC Investigators, Johnson, T., Bergman, S., Bochud, M., Waeber, G., and Vollenweider, P.
Subjects: Netherlands Twin Register (NTR), Male, Adult, African Americans/genetics, Aged, Case-Control Studies, Cohort Studies, Diabetes Mellitus, Type 2/ethnology, Diabetes Mellitus, Type 2/genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Validation Studies as Topic, Medicin och hälsovetenskap, Linkage disequilibrium, Genetic Screens, endocrine system diseases, lcsh:Medicine, Genome-wide association study, Medical and Health Sciences, 0302 clinical medicine, Endocrinology, Genome Sequencing, lcsh:Science, Medicine(all), Genetics, African Americans, 0303 health sciences, education.field_of_study, INSULIN-RESISTANCE, Multidisciplinary, Agricultural and Biological Sciences(all), LARGE-SCALE ASSOCIATION, STAGE RENAL-DISEASE, COMMON VARIANTS, Genomics, Medicine, Research Article, SUSCEPTIBILITY LOCI, General Science & Technology, Population, Single-nucleotide polymorphism, Biology, DIAGRAM Consortium, 03 medical and health sciences, MAGIC Investigators, SDG 3 - Good Health and Well-being, Genetic linkage, MD Multidisciplinary, Genome-Wide Association Studies, SNP, ddc:610, education, Genotyping, 030304 developmental biology, Diabetic Endocrinology, LINKAGE ANALYSIS, Biochemistry, Genetics and Molecular Biology(all), lcsh:R, TCF7L2 GENE, Case-control study, Computational Biology, nutritional and metabolic diseases, Human Genetics, Diabetes Mellitus Type 2, Stage renal-disease, large-scale association, Susceptibility loci, Insulin-resistance, Fasting glucose, Tissue factor, Homeodomain protein, Linkage analysis, Common variants, TCF7L2 gene, Black or African American, Diabetes Mellitus, Type 2, TISSUE FACTOR, Genetics of Disease, HOMEODOMAIN PROTEIN, Genetic Polymorphism, lcsh:Q, Genome Expression Analysis, 030217 neurology & neurosurgery, Population Genetics, FASTING GLUCOSE
Abstract: African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P
Published: 2012

15. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author: Wain, Louise V, Verwoert, Germaine C, O'Reilly, Paul F, Shi, Gang, Johnson, Toby, Johnson, Andrew D, Bochud, Murielle, Rice, Kenneth M, Henneman, Peter, Smith, Albert V, Ehret, Georg B, Amin, Najaf, Larson, Martin G, Mooser, Vincent, Hadley, David, Dörr, Marcus, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile JW, Zhao, Jing Hua, Heath, Simon, Laan, Maris, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'an, Arora, Pankaj, Lucas, Gavin, Pirastu, Nicola, Pichler, Irene, Jackson, Anne U, Webster, Rebecca J, Zhang, Feng, Peden, John F, Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I, Trompet, Stella, Bragg-Gresham, Jennifer L, Alizadeh, Behrooz Z, Chambers, John C, Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M, Polašek, Ozren, Boban, Mladen, Nelson, Christopher P, Morrison, Alanna C, Pihur, Vasyl, Ganesh, Santhi K, Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco US, Rivadeneira, Fernando, Sijbrands, Eric JG, Uitterlinden, Andre G, Hwang, Shih-Jen, Vasan, Ramachandran S, Wang, Thomas J, Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, McArdle, Wendy L, Kroemer, Heyo K, Völker, Uwe, Völzke, Henry, Glazer, Nicole L, Taylor, Kent D, Harris, Tamara B, Alavere, Helene, Haller, Toomas, Keis, Aime, Tammesoo, Mari-Liis, Aulchenko, Yurii, Barroso, Inês, Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M, Penninx, Brenda W, Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, d'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco, Fabiola M, Facheris, Maurizio, Collins, Francis S, Bergman, Richard N, Beilby, John P, Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Anders, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S, Navarro, Pau, Wild, Sarah H, Corsi, Anna Maria, Singleton, Andrew, de Geus, Eco JC, Willemsen, Gonneke, Parker, Alex N, Rose, Lynda M, Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, LifeLines Cohort Study, van der Klauw, Melanie M, Zhang, Weihua, Li, Xinzhong, Scott, James, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thomas, Davies, Gail, Starr, John M, Emilsson, Valur, Plump, Andrew, Lindeman, Jan H, Hoen, Peter AC 't, König, Inke R, EchoGen consortium, Felix, Janine F, Clarke, Robert, Hopewell, Jemma C, Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L, Fornage, Myriam, AortaGen Consortium, Mitchell, Gary F, CHARGE Consortium Heart Failure Working Group, Smith, Nicholas L, KidneyGen consortium, Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, CKDGen consortium, Cardiogenics consortium, CardioGram, Samani, Nilesh J, Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J, Wichmann, H-Erich, Raitakari, Olli T, Palmas, Walter, Kooner, Jaspal S, Stolk, Ronald P, Jukema, J Wouter, Wright, Alan F, Boomsma, Dorret I, Bandinelli, Stefania, Gyllensten, Ulf B, Wilson, James F, Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D, Palmer, Lyle J, Tuomilehto, Jaakko, Pfeufer, Arne, Gasparini, Paolo, Siscovick, David, Altshuler, David, Loos, Ruth JF, Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J, Oostra, Ben A, Metspalu, Andres, Launer, Lenore, Rettig, Rainer, Strachan, David P, Beckmann, Jacques S, Witteman, Jacqueline CM, Erdmann, Jeanette, van Dijk, Ko Willems, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M, Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R, Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B, Psaty, Bruce M, Caulfield, Mark J, Rao, Dabeeru C, Tobin, Martin D, Elliott, Paul, van Duijn, Cornelia M, Zhao, Jing Hua [0000-0003-4930-3582], Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Khaw, Kay-Tee [0000-0002-8802-2903], Soranzo, Nicole [0000-0003-1095-3852], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Genetic Loci, Case-Control Studies, Hypertension, Humans, Blood Pressure, cardiovascular diseases, Arteries, Polymorphism, Single Nucleotide, Linkage Disequilibrium, circulatory and respiratory physiology, Follow-Up Studies, Genome-Wide Association Study
Abstract: Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
Published: 2011

16. Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

Author: Spector, Tim D., Rotimi, Charles N., Hedblad, Bo, Brand, Eva, Day, Ian N. M., Kita, Yoshikuni, Chandak, Giriraj R., Tomaszewski, Maciej, Wong, Andrew, Ogihara, Toshio, Salomaa, Veikko, Igl, Wilmar, Laitinen, Jaana, Olden, Matthias, Okamura, Tomonori, Peltonen, Leena, Witteman, Jacqueline C. M., Wichmann, H-erich, Palmer, Lyle J., Boerwinkle, Eric, Talmud, Philippa J., Tabara, Yasuharu, Platou, Carl G. P., Gyllensten, Ulf B., Meneton, Pierre, Dominiczak, Anna F., Frayling, Timothy M., Groop, Leif, Smith, Albert V., Jackson, Anne U., Kutlar, Abdullah, Heath, Simon, Voight, Benjamin F., Meitinger, Thomas, Stringham, Heather M., Gaunt, Tom R., Islam, Muhammad, Tai, E. Shyong, Hofman, Albert, Lohman, Kurt K., Rotter, Jerome I., Hoffman Bolton, Judith A., Schouw, Yvonne T., Raffel, Leslie J., Lawrence, Robert W., Rudock, Megan E., Scuteri, Angelo, Peden, John F., Eyheramendy, Susana, Aspelund, Thor, Adair, Linda S., Demirkan, Ayse, Staessen, Jan A., Glazer, Nicole L., Launer, Lenore, Ganesh, Santhi, Hirschorn, Joel N., Seshadri, Sudha, Sjo&#776, gren, Marketa, Musani, Solomon K., Verwoert, Germaine C., Umemura, Satoshi, Bis, Joshua C., Dreisbach, Albert W., Keating, Brendan J., Ala-korpela, Mika, Hartikainen, Anna-liisa, Galan, Pilar, Strachan, David P., Hadley, David, Prokopenko, Inga, Young, J. Hunter, Ehret, Georg B., Prabhakaran, Dorairajan, Scott, Laura J., Mosley, Thomas H., Viikari, Jorma, Ohkubo, Takayoshi, Wiggins, Kerri L., Emilsson, Valur, Salako, Tunde, Vo&#776, lker, Uwe, Bornstein, Stefan R., lzke, Henry, Dries, Daniel L., Sharma, Pankaj, Ueshima, Hirotsugu, Wright, Alan F., Lee, Nanette R., Loos, Ruth J. F., Lawlor, Debbie A., Kathiresan, Sekar, Cho, Yoon Shin, Luan, Jian An, Jafar, Tazeen H., Bakker, Stephan J. L., Altshuler, David, Arking, Dan E., Tayo, Bamidele O., Smith, George Davey, Liu, Kiang, Taylor, Herman A., Parsa, Afshin, Mattace-raso, Francesco U. S., Wild, Sarah H., Guo, Xiuqing, Shuldiner, Alan R., Zhang, Weihua, Zhang, Feng, Harris, Tamara B., Kuusisto, Johanna, Zukowska-szczechowska, Ewa, Nyberg, Fredrik, Vineis, Paolo, Dahgam, Santosh, Hayward, Caroline, Hicks, Andrew A., Kuh, Diana, Shriner, Daniel, Taylor, Andrew, Mckenzie, Colin A., Wang, Thomas J., Steinle, Nanette I., Elosua, Roberto, Sim, Xueling, Kang, Sun J., Rivadeneira, Fernando, Palmen, Jutta, Cooper, Matthew N., Lyon, Helen N., Levy, Daniel, Swift, Amy J., Raitakari, Olli, Lyytika&#776, inen, Leo-pekka, Saleheen, Danish, Rudan, Igor, Schwarz, Peter E. H., Kooner, Jaspal S., Smith, Nicholas L., Matullo, Giuseppe, Barroso, Ine&#770, s, O Connell, Jeffrey R., Hunt, Steven C., Hernandez, Dena, Erdmann, Jeanette, Wu&#776, rz, Peter, Forrester, Terrence, Burton, Paul R., Ongen, Halit, Bandinelli, Stefania, Thelle, Dag S., Sehmi, Joban S., O Reilly, Paul F., Braund, Peter S., Danesh, John, Wyatt, Sharon B., Parker, Alex N., Polak, Josef F., Collins, Rory, Zhao, Jing Hua, Shi, Gang, Dehghan, Abbas, Rosengren, Annika, Whincup, Peter H., Duijn, Cornelia M., Hwang, Shih-jen, Ridker, Paul M., Chakravarti, Aravinda, Uda, Manuela, Tanaka, Toshiko, Pramstaller, Peter P., Morken, Mario A., Soininen, Pasi, Abecasis, Gonc&#807, alo R., Zhai, Guangju, Curb, J. David, Ferrucci, Luigi, Doumatey, Ayo P., Fox, Ervin R., Bergman, Richard N., Johnson, Toby, Larson, Martin G., Snieder, Harold, Morris, Richard W., Onland-moret, N. Charlotte, Johnson, Andrew D., Narisu, Narisu, Samani, Nilesh J., Pihur, Vasyl, Chaturvedi, Nish, Melander, Olle, Hamsten, Anders, Charchar, Fadi J., Ludwig, Barbara, Kim, Hyung-lae, Bergmann, Sven, Nalls, Michael A., Milaneschi, Yuri, Palmer, Nicholette D., Alexander, Myriam, Townsend, Raymond R., Caulfield, Mark J., Hilton, Gina, Tuomilehto, Jaakko, Lee, Jong-young, Perola, Markus, Grobbee, Diederick E., Longstreth, Will T., Munroe, Patricia B., Uitterlinden, Andre G., Iwai, Naoharu, Adeyemo, Adebowale, Cooper, Richard S., Mcardle, Wendy L., Sun, Yan V., Sijbrands, Eric J. G., Fabsitz, Richard R., Nguyen, Khanh-dung Hoang, Martin, Lisa W., Wareham, Nicholas J., Brown, Morris J., Wang, Xiaoling, Kuznetsova, Tatiana, Rao, Dabeeru C., Org, Elin, Gilst, Wiek H., Orru, Marco, Oostra, Ben A., Howard, Philip, Wagenknecht, Lynne E., Meschia, James F., Mooser, Vincent, Lehtima&#776, ki, Terho, Wong, Tien Y., Langefeld, Carl D., Bragg-gresham, Jennifer L., Bochud, Murielle, Arora, Pankaj, Kivimaki, Mika, Seielstad, Mark, O Donnell, Chris, Chasman, Daniel I., Farrall, Martin, Polasek, Ozren, Fava, Cristiano, Vitart, Veronique, Mani, K. Radha, Uiterwaal, Cuno S. P. M., Chang, Yen-pei C., Zhu, Haidong, Morrison, Alanna C., Bonnycastle, Lori L., Najjar, Samer, Vollenweider, Peter, Eaton, Charles B., Singleton, Andrew, Teumer, Alexander, Deloukas, Panos, Campbell, Harry, Terzic, Janos, Aulchenko, Yurii, Farlow, Deborah N., Psaty, Bruce M., Beckmann, Jacques S., Scott, James, Tobin, Martin D., Kao, Wen Hong Linda, Harst, Pim, Amin, Najaf, Zitting, Paavo, Pattaro, Cristian, Casas, Juan P., Ikram, M. Arfan, Coresh, Josef, Hingorani, Aroon D., Kulkarni, Smita R., Shrine, Nick R. G., Yao, Jie, Fowkes, F. Gerald R., Clarke, Robert, Gra&#776, ssler, Ju&#776, rgen, Hercberg, Serge, Wain, Louise V., Redline, Susan, Isaacs, Aaron, Hopewell, Jemma C., Lathrop, Mark, Vinay, D. G., Marmot, Michael G., Laan, Maris, Rasheed, Asif, So&#771, ber, Siim, Vartiainen, Erkki, Han, Bok-ghee, Rettig, Rainer, Kinra, Sanjay, Artigas, Maria Soler, Veldre, Gudrun, Navis, Gerjan, Shaw-hawkins, Sue, Franceschini, Nora, Lucas, Gavin, Penman, Alan D., Ong, Rick Twee-hee, Mohlke, Karen L., Beilby, John P., Zhu, Xiaofeng, Bots, Michiel L., Chen, Ming-huei, Denniff, Matthew, Brand, Stefan-martin, Kangas, Antti J., Hveem, Kristian, Chambers, John C., Tukiainen, Taru, Boehnke, Michael, Ramachandran, Vasan S., Connell, John M., Collins, Francis S., Khaw, Kay-tee, Nilsson, Peter, Wilson, James F., Yajnik, Chittaranjan S., Guarrera, Simonetta, Gieger, Christian, Elliott, Paul, Plump, Andrew, Ricceri, Fulvio, Tzoulaki, Ioanna, Garcia, Melissa, Ka&#776, ho&#776, nen, Mika, Laakso, Markku, Kumari, Meena, Stanca&#769, kova&#769, Alena, Corsi, Anna Maria, Soranzo, Nicole, Kettunen, Johannes, Gudnason, Vilmundur, Kardia, Sharon L. R., Hardy, Rebecca, Lakatta, Edward G., Goel, Anuj, Liu, Yongmei, Dong, Yanbin, Humphries, Steve E., Rice, Kenneth M., Newton-cheh, Christopher, Ko&#776, ttgen, Anna, Viigimaa, Margus, Tripathy, Vikal, Mangino, Massimo, Janipalli, Charles S., Heckbert, Susan R., Palmas, Walter, Watkins, Hugh, Do&#776, rr, Marcus, Kroemer, Heyo K., Weder, Alan B., Wu, Ying, Schwartz, Steven M., Miki, Tetsuro, Zelenika, Diana, Cooper, Jackie A., Kumar, M. J. Kranthi, International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), Ja&#776, rvelin, Marjo-riitt, EchoGen consortium, CARDIoGRAM consortium, CKDGen consortium, Charge-hf, Consortium, KidneyGen consortium, Medical Research Council (MRC), Kuznetsova, Tatiana, Staessen, Jan A, Pediatrics, Ehret, Georg Benedikt, International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), CARDIoGRAM consortium, CKDGen consortium, KidneyGen consortium, EchoGen consortium, CHARGE-HF consortium, Morrison, Alanna C [0000-0001-6381-4296], Ramachandran, Vasan S [0000-0001-7357-5970], Adeyemo, Adebowale [0000-0002-3105-3231], Martin, Lisa W [0000-0003-4352-0914], Caulfield, Mark J [0000-0001-9295-3594], Levy, Daniel [0000-0003-1843-8724], Apollo - University of Cambridge Repository, Epidemiologie, and RS: CARIM School for Cardiovascular Diseases
Subjects: Male, Candidate gene, Blood pressure, GWAS, genetic variant, African Americans, Genome-wide association study, Blood Pressure, 030204 cardiovascular system & hematology, Cardiovascular, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, Diastole, 2.1 Biological and endogenous factors, International Consortium for Blood Pressure Genome-wide Association Studies (ICBP-GWAS), European Continental Ancestry Group/genetics, Aetiology, International HapMap Project, International Consortium for Blood Pressure Genome-wide Association Studies, Genetics (clinical), ddc:616, Genetics, Genetics & Heredity, 0303 health sciences, Association Studies Articles, Single Nucleotide, General Medicine, 11 Medical And Health Sciences, Biological Sciences, Middle Aged, 3. Good health, Phenotype, Hypertension, Female, Adult, Genotype, Systole, European Continental Ancestry Group, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, White People, genome-wide association, hypertension prevalence, receptor, disease, family, loci, vasculature, awareness, traits, design, 03 medical and health sciences, Clinical Research, Genetic variation, Humans, Genetic variability, Polymorphism, Hypertension/epidemiology/genetics, Molecular Biology, 030304 developmental biology, Genetic association, Aged, African Americans/genetics, Human Genome, 06 Biological Sciences, Black or African American, Genetic Loci, Genome-Wide Association Study, Hypertension/epidemiology, Hypertension/genetics, Imputation (genetics)
Abstract: The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. ispartof: HUMAN MOLECULAR GENETICS vol:20 issue:11 pages:2273-2284 ispartof: location:England status: published
Published: 2011

17. Distribution of plasma levels of adiponectin and leptin in an adult Caucasian population

Author: Marques-Vidal Pedro, Bochud Murielle, Paccaud Fred, Mooser Vincent, Waeber Gérard, and Vollenweider Peter
Subjects: Adult, Leptin, Male, Population, Age Factors, nutritional and metabolic diseases, Middle Aged, White People, Body Mass Index, Cross-Sectional Studies, Adipose Tissue, Humans, Female, Adiponectin, Menopause, Life Style, hormones, hormone substitutes, and hormone antagonists, Switzerland, Aged
Abstract: OBJECTIVES Little is known regarding the distribution and the determinants of leptin and adiponectin levels in the general population. DESIGN Cross sectional study. PATIENTS Women (3004) and men (2552) aged 35 74 living in Lausanne Switzerland. MEASUREMENTS Plasma levels of leptin and adiponectin (ELISA measurement). RESULTS Women had higher leptin and adiponectin levels than men. In both genders leptin and adiponectin levels increased with age. After adjusting for fat mass leptin levels were significantly and negatively associated with age in women: 18.1 +/ 0.3 17.1 +/ 0.3 16.7 +/ 0.3 and 15.5 +/ 0.4 ng/ml (adjusted mean +/ SE) for age groups [35 44] [45 54] [55 64] and [65 75] respectively P < 0.001. A similar but nonsignificant trend was also found in men. Conversely the age related increase of adiponectin was unrelated to body fat in both genders. Post menopausal women had higher leptin and adiponectin levels than premenopausal women independently of hormone replacement therapy. Although body fat mass was associated with leptin and adiponectin the associations were stronger with body mass index (BMI) waist and hip in both genders. Finally after adjusting for age and anthropometry no relationships were found between leptin or adiponectin levels with alcohol caffeine consumption and physical activity whereas smoking and diabetes decreased leptin and adiponectin levels in women only. CONCLUSIONS The age related increase in leptin levels is attributable to changes in fat mass in women and probably also in men. Leptin and adiponectin levels are more related to BMI than to body fat mass. The effects of smoking and diabetes appear to be gender specific.
Published: 2009

18. Variants in the melatonin receptor 1B gene (MTNR1B) influence fasting glucose levels

Author: Prokopenko, Inga, Langenberg, Claudia, Florez, Jose C., Saxena, Richa, Soranzo, Nicole, Thorleifsson, Gudmar, Loos, Ruth J.F., Manning, Alisa K., Jackson, Anne U., Aulchenko, Yurii, Potter, Simon C., Erdos, Michael R., Sanna, Serena, Hottenga, Jouke-Jan, Wheeler, Eleanor, Kaakinen, Marika, Lyssenko, Valeriya, Chen, Wei-Min, Ahmadi, Kourosh, Beckmann, Jacques S., Bergman, Richard N., Bochud, Murielle, Bonnycastle, Lori L., Buchanan, Thomas A., Cao, Antonio, Cervino, Alessandra, Coin, Lachlan, Collins, Francis S., Crisponi, Laura, de Geus, Eco JC, Dehghan, Abbas, Deloukas, Panos, Doney, Alex S F, Elliott, Paul, Freimer, Nelson, Gateva, Vesela, Herder, Christian, Hofman, Albert, Hughes, Thomas E., Hunt, Sarah, Illig, Thomas, Inouye, Michael, Isomaa, Bo, Johnson, Toby, Kong, Augustine, Krestyaninova, Maria, Kuusisto, Johanna, Laakso, Markku, Lim, Noha, Lindblad, Ulf, Lindgren, Cecilia M., McCann, Owen T., Mohlke, Karen L., Morris, Andrew D, Naitza, Silvia, Orrù, Marco, Palmer, Colin N A, Pouta, Anneli, Randall, Joshua, Rathmann, Wolfgang, Saramies, Jouko, Scheet, Paul, Scott, Laura J., Scuteri, Angelo, Sharp, Stephen, Sijbrands, Eric, Smit, Jan H., Song, Kijoung, Steinthorsdottir, Valgerdur, Stringham, Heather M., Tuomi, Tiinamaija, Tuomilehto, Jaakko, Uitterlinden, André G., Voight, Benjamin F., Waterworth, Dawn, Wichmann, H.-Erich, Willemsen, Gonneke, Witteman, Jacqueline CM, Yuan, Xin, Zhao, Jing Hua, Zeggini, Eleftheria, Schlessinger, David, Sandhu, Manjinder, Boomsma, Dorret I, Uda, Manuela, Spector, Tim D., Penninx, Brenda WJH, Altshuler, David, Vollenweider, Peter, Jarvelin, Marjo Riitta, Lakatta, Edward, Waeber, Gerard, Fox, Caroline S., Peltonen, Leena, Groop, Leif C., Mooser, Vincent, Cupples, L. Adrienne, Thorsteinsdottir, Unnur, Boehnke, Michael, Barroso, Inês, Van Duijn, Cornelia, Dupuis, Josée, Watanabe, Richard M., Stefansson, Kari, McCarthy, Mark I., Wareham, Nicholas J., Meigs, James B., and Abecasis, Goncalo R.
Subjects: Blood Glucose, Diabetes Mellitus, Type 2, Meta-Analysis as Topic, Receptor, Melatonin, MT2, Case-Control Studies, Quantitative Trait Loci, Receptors, Melatonin, Humans, Genetic Predisposition to Disease, Fasting, Polymorphism, Single Nucleotide, Article, Genome-Wide Association Study
Abstract: To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
Published: 2008

19. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals

Author: Dastani, Zari, Hivert, Marie-France, Timpson, Nicholas, Perry, John RB, Yuan, Xin, Scott, Robert A, Henneman, Peter, Heid, Iris M, Kizer, Jorge R, Lyytikäinen, Leo-Pekka, Fuchsberger, Christian, Tanaka, Toshiko, Morris, Andrew P, Small, Kerrin, Isaacs, Aaron, Beekman, Marian, Coassin, Stefan, Lohman, Kurt, Qi, Lu, Kanoni, Stavroula, Pankow, James S, Uh, Hae-Won, Wu, Ying, Bidulescu, Aurelian, Rasmussen-Torvik, Laura J, Greenwood, Celia MT, Ladouceur, Martin, Grimsby, Jonna, Manning, Alisa K, Liu, Ching-Ti, Kooner, Jaspal, Mooser, Vincent E, Vollenweider, Peter, Kapur, Karen A, Chambers, John, Wareham, Nicholas J, Langenberg, Claudia, Frants, Rune, Willems-Vandijk, Ko, Oostra, Ben A, Willems, Sara M, Lamina, Claudia, Winkler, Thomas W, Psaty, Bruce M, Tracy, Russell P, Brody, Jennifer, Chen, Ida, Viikari, Jorma, Kähönen, Mika, Pramstaller, Peter P, Evans, David M, St Pourcain, Beate, Sattar, Naveed, Wood, Andrew R, Bandinelli, Stefania, Carlson, Olga D, Egan, Josephine M, Böhringer, Stefan, Van Heemst, Diana, Kedenko, Lyudmyla, Kristiansson, Kati, Nuotio, Marja-Liisa, Loo, Britt-Marie, Harris, Tamara, Garcia, Melissa, Kanaya, Alka, Haun, Margot, Klopp, Norman, Wichmann, H-Erich, Deloukas, Panos, Katsareli, Efi, Couper, David J, Duncan, Bruce B, Kloppenburg, Margreet, Adair, Linda S, Borja, Judith B, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, Wilson, James G, Musani, Solomon, Guo, Xiuqing, Johnson, Toby, Semple, Robert, Teslovich, Tanya M, Allison, Matthew A, Redline, Susan, Buxbaum, Sarah G, Mohlke, Karen L, Meulenbelt, Ingrid, Ballantyne, Christie M, Dedoussis, George V, Hu, Frank B, Liu, Yongmei, Paulweber, Bernhard, Spector, Timothy D, Slagboom, P Eline, Ferrucci, Luigi, Jula, Antti, Perola, Markus, Raitakari, Olli, Florez, Jose C, Salomaa, Veikko, Eriksson, Johan G, Frayling, Timothy M, Hicks, Andrew A, Lehtimäki, Terho, Smith, George Davey, Siscovick, David S, Kronenberg, Florian, Van Duijn, Cornelia, Loos, Ruth JF, Waterworth, Dawn M, Meigs, James B, Dupuis, Josee, Richards, J Brent, Voight, Benjamin F, Scott, Laura J, Steinthorsdottir, Valgerdur, Dina, Christian, Welch, Ryan P, Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S, Thorleifsson, Gudmar, McCulloch, Laura J, Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J, Raychaudhuri, Soumya, McCarroll, Steve A, Hofmann, Oliver M, Segrè, Ayellet V, Van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Benediktsson, Rafn, Bennett, Amanda J, Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L, Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P, Charpentier, Guillaume, Chines, Peter S, Cornelis, Marilyn, Crawford, Gabe, Doney, Alex SF, Elliott, Katherine S, Elliott, Amanda L, Erdos, Michael R, Fox, Caroline S, Franklin, Christopher S, Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J, Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U, Johnson, Paul RV, Jørgensen, Torben, Kao, Wen HL, Kong, Augustine, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Aloysius, Lindgren, Cecilia M, Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, Midthjell, Kristian, Morken, Mario A, Narisu, Narisu, Nilsson, Peter, Owen, Katharine R, Payne, Felicity, Petersen, Ann-Kristin, Platou, Carl, Proença, Christine, Prokopenko, Inga, Rathmann, Wolfgang, Rayner, N William, Robertson, Neil R, Rocheleau, Ghislain, Roden, Michael, Sampson, Michael J, Saxena, Richa, Shields, Beverley M, Shrader, Peter, Sigurdsson, Gunnar, Sparsø, Thomas, Strassburger, Klaus, Stringham, Heather M, Sun, Qi, Swift, Amy J, Thorand, Barbara, Tichet, Jean, Tuomi, Tiinamaija, Van Dam, Rob M, Van Haeften, Timon W, Van Herpt, Thijs, Van Vliet-Ostaptchouk, Jana V, Walters, G Bragi, Weedon, Michael N, Wijmenga, Cisca, Witteman, Jacqueline, Bergman, Richard N, Cauchi, Stephane, Collins, Francis S, Gloyn, Anna L, Gyllensten, Ulf, Hansen, Torben, Hide, Winston A, Hitman, Graham A, Hofman, Albert, Hunter, David J, Hveem, Kristian, Laakso, Markku, Morris, Andrew D, Palmer, Colin NA, Rudan, Igor, Sijbrands, Eric, Stein, Lincoln D, Tuomilehto, Jaakko, Uitterlinden, Andre, Walker, Mark, Watanabe, Richard M, Abecasis, Goncalo R, Boehm, Bernhard O, Campbell, Harry, Daly, Mark J, Hattersley, Andrew T, Pedersen, Oluf, Barroso, Inês, Groop, Leif, Sladek, Rob, Thorsteinsdottir, Unnur, Wilson, James F, Illig, Thomas, Froguel, Philippe, Van Duijn, Cornelia M, Stefansson, Kari, Altshuler, David, Boehnke, Michael, McCarthy, Mark I, Soranzo, Nicole, Wheeler, Eleanor, Glazer, Nicole L, Bouatia-Naji, Nabila, Mägi, Reedik, Randall, Joshua, Elliott, Paul, Rybin, Denis, Dehghan, Abbas, Hottenga, Jouke Jan, Song, Kijoung, Goel, Anuj, Lajunen, Taina, Doney, Alex, Cavalcanti-Proença, Christine, Kumari, Meena, Timpson, Nicholas J, Zabena, Carina, Ingelsson, Erik, An, Ping, O'Connell, Jeffrey, Luan, Jian'an, Elliott, Amanda, McCarroll, Steven A, Roccasecca, Rosa Maria, Pattou, François, Sethupathy, Praveen, Ariyurek, Yavuz, Barter, Philip, Beilby, John P, Ben-Shlomo, Yoav, Bergmann, Sven, Bochud, Murielle, Bonnefond, Amélie, Borch-Johnsen, Knut, Böttcher, Yvonne, Brunner, Eric, Bumpstead, Suzannah J, Chen, Yii-Der Ida, Chines, Peter, Clarke, Robert, Coin, Lachlan JM, Cooper, Matthew N, Crisponi, Laura, Day, Ian NM, De Geus, Eco JC, Delplanque, Jerome, Fedson, Annette C, Fischer-Rosinsky, Antje, Forouhi, Nita G, Franzosi, Maria Grazia, Galan, Pilar, Goodarzi, Mark O, Graessler, Jürgen, Grundy, Scott, Gwilliam, Rhian, Hallmans, Göran, Hammond, Naomi, Han, Xijing, Hartikainen, Anna-Liisa, Hayward, Caroline, Heath, Simon C, Hercberg, Serge, Hillman, David R, Hingorani, Aroon D, Hui, Jennie, Hung, Joe, Kaakinen, Marika, Kaprio, Jaakko, Kesaniemi, Y Antero, Kivimaki, Mika, Knight, Beatrice, Koskinen, Seppo, Kovacs, Peter, Kyvik, Kirsten Ohm, Lathrop, G Mark, Lawlor, Debbie A, Le Bacquer, Olivier, Lecoeur, Cécile, Li, Yun, Mahley, Robert, Mangino, Massimo, Martínez-Larrad, María Teresa, McAteer, Jarred B, McPherson, Ruth, Meisinger, Christa, Melzer, David, Meyre, David, Mitchell, Braxton D, Mukherjee, Sutapa, Naitza, Silvia, Neville, Matthew J, Orrù, Marco, Pakyz, Ruth, Paolisso, Giuseppe, Pattaro, Cristian, Pearson, Daniel, Peden, John F, Pedersen, Nancy L, Pfeiffer, Andreas FH, Pichler, Irene, Polasek, Ozren, Posthuma, Danielle, Potter, Simon C, Pouta, Anneli, Province, Michael A, Rayner, Nigel W, Rice, Kenneth, Ripatti, Samuli, Rivadeneira, Fernando, Rolandsson, Olov, Sandbaek, Annelli, Sandhu, Manjinder, Sanna, Serena, Sayer, Avan Aihie, Scheet, Paul, Seedorf, Udo, Sharp, Stephen J, Shields, Beverley, Sigurðsson, Gunnar, Sijbrands, Eric JG, Silveira, Angela, Simpson, Laila, Singleton, Andrew, Smith, Nicholas L, Sovio, Ulla, Swift, Amy, Syddall, Holly, Syvänen, Ann-Christine, Tönjes, Anke, Uitterlinden, André G, Van Dijk, Ko Willems, Varma, Dhiraj, Visvikis-Siest, Sophie, Vitart, Veronique, Vogelzangs, Nicole, Waeber, Gérard, Wagner, Peter J, Walley, Andrew, Ward, Kim L, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Witteman, Jaqueline CM, Yarnell, John WG, Zelenika, Diana, Zethelius, Björn, Zhai, Guangju, Zhao, Jing Hua, Zillikens, M Carola, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Borecki, Ingrid B, Meneton, Pierre, Magnusson, Patrik KE, Nathan, David M, Williams, Gordon H, Silander, Kaisa, Bornstein, Stefan R, Schwarz, Peter, Spranger, Joachim, Karpe, Fredrik, Shuldiner, Alan R, Cooper, Cyrus, Serrano-Ríos, Manuel, Lind, Lars, Palmer, Lyle J, Franks, Paul W, Ebrahim, Shah, Marmot, Michael, Kao, WH Linda, Pramstaller, Peter Paul, Wright, Alan F, Stumvoll, Michael, Hamsten, Anders, Procardis Consortium, Buchanan, Thomas A, Valle, Timo T, Rotter, Jerome I, Penninx, Brenda WJH, Boomsma, Dorret I, Cao, Antonio, Scuteri, Angelo, Schlessinger, David, Uda, Manuela, Ruokonen, Aimo, Jarvelin, Marjo-Riitta, Peltonen, Leena, Mooser, Vincent, Sladek, Robert, MAGIC Investigators, GLGC Consortium, Musunuru, Kiran, Smith, Albert V, Edmondson, Andrew C, Stylianou, Ioannis M, Koseki, Masahiro, Pirruccello, James P, Chasman, Daniel I, Johansen, Christopher T, Fouchier, Sigrid W, Peloso, Gina M, Barbalic, Maja, Ricketts, Sally L, Bis, Joshua C, Feitosa, Mary F, Orho-Melander, Marju, Melander, Olle, Li, Xiaohui, Li, Mingyao, Cho, Yoon Shin, Go, Min Jin, Kim, Young Jin, Lee, Jong-Young, Park, Taesung, Kim, Kyunga, Sim, Xueling, Ong, Rick Twee-Hee, Croteau-Chonka, Damien C, Lange, Leslie A, Smith, Joshua D, Ziegler, Andreas, Zhang, Weihua, Zee, Robert YL, Whitfield, John B, Thompson, John R, Surakka, Ida, Spector, Tim D, Smit, Johannes H, Sinisalo, Juha, Scott, James, Saharinen, Juha, Sabatti, Chiara, Rose, Lynda M, Roberts, Robert, Rieder, Mark, Parker, Alex N, Pare, Guillaume, O'Donnell, Christopher J, Nieminen, Markku S, Nickerson, Deborah A, Montgomery, Grant W, McArdle, Wendy, Masson, David, Martin, Nicholas G, Marroni, Fabio, Lucas, Gavin, Luben, Robert, Lokki, Marja-Liisa, Lettre, Guillaume, Launer, Lenore J, Lakatta, Edward G, Laaksonen, Reijo, Kyvik, Kirsten O, König, Inke R, Khaw, Kay-Tee, Kaplan, Lee M, Johansson, Åsa, Janssens, A Cecile JW, Igl, Wilmar, Hovingh, G Kees, Hengstenberg, Christian, Havulinna, Aki S, Hastie, Nicholas D, Harris, Tamara B, Haritunians, Talin, Hall, Alistair S, Groop, Leif C, Gonzalez, Elena, Freimer, Nelson B, Erdmann, Jeanette, Ejebe, Kenechi G, Döring, Angela, Dominiczak, Anna F, Demissie, Serkalem, Deloukas, Panagiotis, De Faire, Ulf, Crawford, Gabriel, Chen, Yii-Der I, Caulfield, Mark J, Boekholdt, S Matthijs, Assimes, Themistocles L, Quertermous, Thomas, Seielstad, Mark, Wong, Tien Y, Tai, E-Shyong, Feranil, Alan B, Kuzawa, Christopher W, Taylor, Herman A, Gabriel, Stacey B, Holm, Hilma, Gudnason, Vilmundur, Krauss, Ronald M, Ordovas, Jose M, Munroe, Patricia B, Kooner, Jaspal S, Tall, Alan R, Hegele, Robert A, Kastelein, John JP, Schadt, Eric E, Strachan, David P, Reilly, Muredach P, Samani, Nilesh J, Schunkert, Heribert, Cupples, L Adrienne, Sandhu, Manjinder S, Ridker, Paul M, Rader, Daniel J, and Kathiresan, Sekar
Subjects: 2. Zero hunger, Male, Waist-Hip Ratio, Cholesterol, HDL, Gene Expression, Glucose Tolerance Test, Polymorphism, Single Nucleotide, White People, 3. Good health, Black or African American, Asian People, Diabetes Mellitus, Type 2, Humans, Female, Genetic Predisposition to Disease, Adiponectin, Insulin Resistance, Metabolic Networks and Pathways, Genome-Wide Association Study
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p

20. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author: International Consortium For Blood Pressure Genome-Wide Association Studies, Ehret, Georg B, Munroe, Patricia B, Rice, Kenneth M, Bochud, Murielle, Johnson, Andrew D, Chasman, Daniel I, Smith, Albert V, Tobin, Martin D, Verwoert, Germaine C, Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F, Amin, Najaf, Bragg-Gresham, Jennifer L, Teumer, Alexander, Glazer, Nicole L, Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sõber, Siim, Parsa, Afshin, Luan, Jian'an, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A, Jackson, Anne U, Peden, John F, Tanaka, Toshiko, Wild, Sarah H, Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N, Fava, Cristiano, Chambers, John C, Fox, Ervin R, Kumari, Meena, Go, Min Jin, Van Der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, DG, Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H, Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Nguyen, Khanh-Dung Hoang, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R, Onland-Moret, N Charlotte, Cooper, Matthew N, Platou, Carl GP, Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S, Kuznetsova, Tatiana, Uiterwaal, Cuno SPM, Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D, CARDIoGRAM Consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen Consortium, CHARGE-HF Consortium, Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C, O'Connell, Jeffrey R, Steinle, Nanette I, Grobbee, Diederick E, Arking, Dan E, Kardia, Sharon L, Morrison, Alanna C, Hernandez, Dena, Najjar, Samer, McArdle, Wendy L, Hadley, David, Brown, Morris J, Connell, John M, Hingorani, Aroon D, Day, Ian NM, Lawlor, Debbie A, Beilby, John P, Lawrence, Robert W, Clarke, Robert, Hopewell, Jemma C, Ongen, Halit, Dreisbach, Albert W, Li, Yali, Young, J Hunter, Bis, Joshua C, Kähönen, Mika, Viikari, Jorma, Adair, Linda S, Lee, Nanette R, Chen, Ming-Huei, Olden, Matthias, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M, Islam, Muhammad, Jafar, Tazeen H, Erdmann, Jeanette, Kulkarni, Smita R, Bornstein, Stefan R, Grässler, Jürgen, Groop, Leif, Voight, Benjamin F, Kettunen, Johannes, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inês, Khaw, Kay-Tee, Weder, Alan B, Hunt, Steven C, Sun, Yan V, Bergman, Richard N, Collins, Francis S, Bonnycastle, Lori L, Scott, Laura J, Stringham, Heather M, Peltonen, Leena, Perola, Markus, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A, Wang, Thomas J, Burton, Paul R, Soler Artigas, Maria, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K, Rudock, Megan E, Heckbert, Susan R, Smith, Nicholas L, Wiggins, Kerri L, Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margus, Kinra, Sanjay, Prabhakaran, Dorairaj, Tripathy, Vikal, Langefeld, Carl D, Rosengren, Annika, Thelle, Dag S, Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, McKenzie, Colin A, Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thomas, Wichmann, H-Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, James, Sehmi, Joban S, Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J, Yao, Jie, Kathiresan, Sekar, O'Donnell, Christopher J, Schwartz, Stephen M, Ikram, M Arfan, Longstreth, WT, Mosley, Thomas H, Seshadri, Sudha, Shrine, Nick RG, Wain, Louise V, Morken, Mario A, Swift, Amy J, Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A, Humphries, Steve E, Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Anders, Watkins, Hugh, Bakker, Stephan JL, Van Gilst, Wiek H, Janipalli, Charles S, Mani, K Radha, Yajnik, Chittaranjan S, Hofman, Albert, Mattace-Raso, Francesco US, Oostra, Ben A, Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G, Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J, Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Ong, Rick Twee-Hee, Dörr, Marcus, Kroemer, Heyo K, Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Panos, Mangino, Massimo, Spector, Tim D, Zhai, Guangju, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Terzic, Janos, Kumar, MV Kranthi, Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E, Fowkes, F Gerald R, Charchar, Fadi J, Schwarz, Peter EH, Hayward, Caroline, Guo, Xiuqing, Rotimi, Charles, Bots, Michiel L, Brand, Eva, Samani, Nilesh J, Polasek, Ozren, Talmud, Philippa J, Nyberg, Fredrik, Kuh, Diana, Laan, Maris, Hveem, Kristian, Palmer, Lyle J, Van Der Schouw, Yvonne T, Casas, Juan P, Mohlke, Karen L, Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K, Wong, Tien Y, Tai, E Shyong, Cooper, Richard S, Laakso, Markku, Rao, Dabeeru C, Harris, Tamara B, Morris, Richard W, Dominiczak, Anna F, Kivimaki, Mika, Marmot, Michael G, Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R, Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S, Melander, Olle, Ridker, Paul M, Bandinelli, Stefania, Gyllensten, Ulf B, Wright, Alan F, Wilson, James F, Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P, Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric JG, Altshuler, David, Loos, Ruth JF, Shuldiner, Alan R, Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G, Wareham, Nicholas J, Gudnason, Vilmundur, Rotter, Jerome I, Rettig, Rainer, Uda, Manuela, Strachan, David P, Witteman, Jacqueline CM, Hartikainen, Anna-Liisa, Beckmann, Jacques S, Boerwinkle, Eric, Vasan, Ramachandran S, Boehnke, Michael, Larson, Martin G, Järvelin, Marjo-Riitta, Psaty, Bruce M, Abecasis, Gonçalo R, Chakravarti, Aravinda, Elliott, Paul, Van Duijn, Cornelia M, Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J, and Johnson, Toby
Subjects: Asia, Blood Pressure, Coronary Artery Disease, Polymorphism, Single Nucleotide, 3. Good health, Europe, Stroke, Cardiovascular Diseases, Africa, Hypertension, Humans, Genetic Predisposition to Disease, Kidney Diseases, Genome-Wide Association Study
Abstract: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

21. A first update on mapping the human genetic architecture of COVID-19

Author: COVID-19 Host Genetics Initiative, Pathak, GA, Karjalainen, J, Stevens, C, Neale, BM, Daly, M, Ganna, A, Andrews, SJ, Kanai, M, Cordioli, M, Polimanti, R, Harerimana, N, Pirinen, M, Liao, RG, Chwialkowska, K, Trankiem, A, Balaconis, MK, Nguyen, H, Solomonson, M, Veerapen, K, Wolford, B, Roberts, G, Park, D, Ball, CA, Coignet, M, McCurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Hong, EL, Rand, K, Girshick, A, Guturu, H, Baltzell, AH, Niemi, MEK, Rahmouni, S, Guntz, J, Beguin, Y, Pigazzini, S, Nkambule, L, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Azarzar, S, Gofflot, S, Claassen, S, Malaise, O, Huynen, P, Meuris, C, Thys, M, Jacques, J, Leonard, P, Frippiat, F, Giot, J-B, Sauvage, A-S, Frenckell, CV, Belhaj, Y, Lambermont, B, Nakanishi, T, Morrison, DR, Mooser, V, Richards, JB, Butler-Laporte, G, Forgetta, V, Li, R, Ghosh, B, Laurent, L, Belisle, A, Henry, D, Abdullah, T, Adeleye, O, Mamlouk, N, Kimchi, N, Afrasiabi, Z, Rezk, N, Vulesevic, B, Bouab, M, Guzman, C, Petitjean, L, Tselios, C, Xue, X, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Brassard, N, Durand, M, Schurr, E, Lepage, P, Ragoussis, J, Auld, D, Chassé, M, Kaufmann, DE, Lathrop, GM, Adra, D, Hayward, C, Glessner, JT, Shaw, DM, Campbell, A, Morris, M, Hakonarson, H, Porteous, DJ, Below, J, Richmond, A, Chang, X, Polikowski, H, Lauren, PE, Chen, H-H, Wanying, Z, Fawns-Ritchie, C, North, K, McCormick, JB, Glessner, JR, Gignoux, CR, Wicks, SJ, Crooks, K, Barnes, KC, Daya, M, Shortt, J, Rafaels, N, Chavan, S, Timmers, PRHJ, Wilson, JF, Tenesa, A, Kerr, SM, D’Mellow, K, Shahin, D, El-Sherbiny, YM, von Hohenstaufen, KA, Sobh, A, Eltoukhy, MM, Nkambul, L, Elhadidy, TA, Abd Elghafar, MS, El-Jawhari, JJ, Mohamed, AAS, Elnagdy, MH, Samir, A, Abdel-Aziz, M, Khafaga, WT, El-Lawaty, WM, Torky, MS, El-shanshory, MR, Yassen, AM, Hegazy, MAF, Okasha, K, Eid, MA, Moahmed, HS, Medina-Gomez, C, Ikram, MA, Uitterlinden, AG, Mägi, R, Milani, L, Metspalu, A, Laisk, T, Läll, K, Lepamets, M, Esko, T, Reimann, E, Naaber, P, Laane, E, Pesukova, J, Peterson, P, Kisand, K, Tabri, J, Allos, R, Hensen, K, Starkopf, J, Ringmets, I, Tamm, A, Kallaste, A, Alavere, H, Metsalu, K, Puusepp, M, Batini, C, Tobin, MD, Venn, LD, Lee, PH, Shrine, N, Williams, AT, Guyatt, AL, John, C, Packer, RJ, Ali, A, Free, RC, Wang, X, Wain, LV, Hollox, EJ, Bee, CE, Adams, EL, Palotie, A, Ripatti, S, Ruotsalainen, S, Kristiansson, K, Koskelainen, S, Perola, M, Donner, K, Kivinen, K, Kaunisto, M, Rivolta, C, Bochud, P-Y, Bibert, S, Boillat, N, Nussle, SG, Albrich, W, Quinodoz, M, Kamdar, D, Suh, N, Neofytos, D, Erard, V, Voide, C, Friolet, R, Vollenweider, P, Pagani, JL, Oddo, M, zu Bentrup, FM, Conen, A, Clerc, O, Marchetti, O, Guillet, A, Guyat-Jacques, C, Foucras, S, Rime, M, Chassot, J, Jaquet, M, Viollet, RM, Lannepoudenx, Y, Portopena, L, Bochud, PY, Desgranges, F, Filippidis, P, Guéry, B, Haefliger, D, Kampouri, EE, Manuel, O, Munting, A, Papadimitriou-Olivgeris, M, Regina, J, Rochat-Stettler, L, Suttels, V, Tadini, E, Tschopp, J, Van Singer, M, Viala, B, Boillat-Blanco, N, Brahier, T, Hügli, O, Meuwly, JY, Pantet, O, Gonseth Nussle, S, Bochud, M, D’Acremont, V, Estoppey Younes, S, Albrich, WC, Cerny, A, O’Mahony, L, von Mering, C, Frischknecht, M, Kleger, G-R., Filipovic, M, Kahlert, CR, Wozniak, H, Negro, TR, Pugin, J, Bouras, K, Knapp, C, Egger, T, Perret, A, Montillier, P, di Bartolomeo, C, Barda, B, de Cid, R, Carreras, A, Moreno, V, Kogevinas, M, Galván-Femenía, I, Blay, N, Farré, X, Sumoy, L, Cortés, B, Mercader, JM, Guindo-Martinez, M, Torrents, D, Garcia-Aymerich, J, Castaño-Vinyals, G, Dobaño, C, Gori, M, Renieri, A, Mari, F, Mondelli, MU, Castelli, F, Vaghi, M, Rusconi, S, Montagnani, F, Bargagli, E, Franchi, F, Mazzei, MA, Cantarini, L, Tacconi, D, Feri, M, Scala, R, Spargi, G, Nencioni, C, Bandini, M, Caldarelli, GP, Canaccini, A, Ognibene, A, D’Arminio Monforte, A, Girardis, M, Antinori, A, Francisci, D, Schiaroli, E, Scotton, PG, Panese, S, Scaggiante, R, Monica, MD, Capasso, M, Fiorentino, G, Castori, M, Aucella, F, Biagio, AD, Masucci, L, Valente, S, Mandalà, M, Zucchi, P, Giannattasio, F, Coviello, DA, Mussini, C, Tavecchia, L, Crotti, L, Rizzi, M, Rovere, MTL, Sarzi-Braga, S, Bussotti, M, Ravaglia, S, Artuso, R, Perrella, A, Romani, D, Bergomi, P, Catena, E, Vincenti, A, Ferri, C, Grassi, D, Pessina, G, Tumbarello, M, Pietro, MD, Sabrina, R, Luchi, S, Furini, S, Dei, S, Benetti, E, Picchiotti, N, Sanarico, M, Ceri, S, Pinoli, P, Raimondi, F, Biscarini, F, Stella, A, Zguro, K, Capitani, K, Tanfoni, M, Fallerini, C, Daga, S, Baldassarri, M, Fava, F, Frullanti, E, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Mencarelli, MA, Rizzo, CL, Pinto, AM, Beligni, G, Tommasi, A, Sarno, LD, Palmieri, M, Carriero, ML, Alaverdian, D, Busani, S, Bruno, R, Vecchia, M, Belli, MA, Mantovani, S, Ludovisi, S, Quiros-Roldan, E, Antoni, MD, Zanella, I, Siano, M, Emiliozzi, A, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Guerrini, S, Conticini, E, Frediani, B, Spertilli, C, Donati, A, Guidelli, L, Corridi, M, Croci, L, Piacentini, P, Desanctis, E, Cappelli, S, Verzuri, A, Anemoli, V, Pancrazzi, A, Lorubbio, M, Miraglia, FG, Venturelli, S, Cossarizza, A, Vergori, A, Gabrieli, A, Riva, A, Paciosi, F, Andretta, F, Gatti, F, Parisi, SG, Baratti, S, Piscopo, C, Russo, R, Andolfo, I, Iolascon, A, Carella, M, Merla, G, Squeo, GM, Raggi, P, Marciano, C, Perna, R, Bassetti, M, Sanguinetti, M, Giorli, A, Salerni, L, Parravicini, P, Menatti, E, Trotta, T, Coiro, G, Lena, F, Martinelli, E, Mancarella, S, Gabbi, C, Maggiolo, F, Ripamonti, D, Bachetti, T, Suardi, C, Parati, G, Bottà, G, Domenico, PD, Rancan, I, Bianchi, F, Colombo, R, Barbieri, C, Acquilini, D, Andreucci, E, Segala, FV, Tiseo, G, Falcone, M, Lista, M, Poscente, M, Vivo, OD, Petrocelli, P, Guarnaccia, A, Baroni, S, van Heel, DA, Hunt, KA, Trembath, RC, Huang, QQ, Martin, HC, Mason, D, Trivedi, B, Wright, J, Finer, S, Akhtar, S, Anwar, M, Arciero, E, Ashraf, S, Breen, G, Chung, R, Curtis, CJ, Chowdhury, M, Colligan, G, Deloukas, P, Durham, C, Griffiths, C, Hurles, M, Hussain, S, Islam, K, Khan, A, Lavery, C, Lee, SH, Lerner, R, MacArthur, D, MacLaughlin, B, Martin, H, Miah, S, Newman, B, Safa, N, Tahmasebi, F, Griffiths, CJ, Smith, AV, Boughton, AP, Li, KW, LeFaive, J, Annis, A, Niavarani, A, Aliannejad, R, Sharififard, B, Amirsavadkouhi, A, Naderpour, Z, Tadi, HA, Aleagha, AE, Ahmadi, S, Moghaddam, SBM, Adamsara, A, Saeedi, M, Abdollahi, H, Hosseini, A, Chariyavilaskul, P, Jantarabenjakul, W, Hirankarn, N, Chamnanphon, M, Suttichet, TB, Shotelersuk, V, Pongpanich, M, Phokaew, C, Chetruengchai, W, Putchareon, O, Torvorapanit, P, Puthanakit, T, Suchartlikitwong, P, Nilaratanakul, V, Sodsai, P, Brumpton, BM, Hveem, K, Willer, C, Zhou, W, Rogne, T, Solligard, E, Åsvold, BO, Franke, L, 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Susanna, Meloni, Ilaria, Mencarelli, Maria Antonietta, Rizzo, Caterina Lo, Pinto, Anna Maria, Beligni, Giada, Tommasi, Andrea, Sarno, Laura Di, Palmieri, Maria, Carriero, Miriam Lucia, Alaverdian, Diana, Busani, Stefano, Bruno, Raffaele, Vecchia, Marco, Belli, Mary Ann, Mantovani, Stefania, Ludovisi, Serena, Quiros-Roldan, Eugenia, Antoni, Melania Degli, Zanella, Isabella, Siano, Matteo, Emiliozzi, Arianna, Fabbiani, Massimiliano, Rossetti, Barbara, Bergantini, Laura, D’Alessandro, Miriana, Cameli, Paolo, Bennett, David, Anedda, Federico, Marcantonio, Simona, Scolletta, Sabino, Guerrini, Susanna, Conticini, Edoardo, Frediani, Bruno, Spertilli, Chiara, Donati, Alice, Guidelli, Luca, Corridi, Marta, Croci, Leonardo, Piacentini, Paolo, Desanctis, Elena, Cappelli, Silvia, Verzuri, Agnese, Anemoli, Valentina, Pancrazzi, Alessandro, Lorubbio, Maria, Miraglia, Federica Gaia, Venturelli, Sophie, Cossarizza, Andrea, Vergori, Alessandra, Gabrieli, Arianna, Riva, Agostino, Paciosi, Francesco, Andretta, Francesca, Gatti, Francesca, Parisi, Saverio Giuseppe, Baratti, Stefano, Piscopo, Carmelo, Russo, Roberta, Andolfo, Immacolata, Iolascon, Achille, Carella, Massimo, Merla, Giuseppe, Squeo, Gabriella Maria, Raggi, Pamela, Marciano, Carmen, Perna, Rita, Bassetti, Matteo, Sanguinetti, Maurizio, Giorli, Alessia, Salerni, Lorenzo, Parravicini, Pierpaolo, Menatti, Elisabetta, Trotta, Tullio, Coiro, Gabriella, Lena, Fabio, Martinelli, Enrico, Mancarella, Sandro, Gabbi, Chiara, Maggiolo, Franco, Ripamonti, Diego, Bachetti, Tiziana, Suardi, Claudia, Parati, Gianfranco, Bottà, Giordano, Domenico, Paolo Di, Rancan, Ilaria, Bianchi, Francesco, Colombo, Riccardo, Barbieri, Chiara, Acquilini, Donatella, Andreucci, Elena, Segala, Francesco Vladimiro, Tiseo, Giusy, Falcone, Marco, Lista, Mirjam, Poscente, Monica, Vivo, Oreste De, Petrocelli, Paola, Guarnaccia, Alessandra, Baroni, Silvia, van Heel, David A., Hunt, Karen A., Trembath, Richard C., Huang, Qin Qin, Martin, Hilary C., Mason, Dan, 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Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Putchareon, Opa, Torvorapanit, Pattama, Puthanakit, Thanyawee, Suchartlikitwong, Pintip, Nilaratanakul, Voraphoj, Sodsai, Pimpayao, Brumpton, Ben M., Hveem, Kristian, Willer, Cristen, Zhou, Wei, Rogne, Tormod, Solligard, Erik, Åsvold, Bjørn Olav, Franke, Lude, Boezen, Marike, Deelen, Patrick, Claringbould, Annique, Lopera, Esteban, Warmerdam, Robert, Vonk, Judith. M., van Blokland, Irene, Lanting, Pauline, Ori, Anil P. S., Feng, Yen-Chen Anne, Mercader, Josep, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Green, Robert C., Perez, Emma F., Zöllner, Sebastian, Wang, Jiongming, Beck, Andrew, Sloofman, Laura G., Ascolillo, Steven, Sebra, Robert P., Collins, Brett L., Levy, Te, Buxbaum, Joseph D., Sealfon, Stuart C., Jordan, Daniel M., Thompson, Ryan C., Gettler, Kyle, Chaudhary, Kumardeep, Belbin, Gillian M., Preuss, Michael, Hoggart, Clive, Choi, Sam, Underwood, Slayton J., Salib, Irene, Britvan, Bari, Keller, Katherine, Tang, Lara, Peruggia, Michael, Hiester, Liam L., Niblo, Kristi, Aksentijevich, Alexandra, Labkowsky, Alexander, Karp, Avromie, Zlatopolsky, Menachem, Zyndorf, Marissa, Charney, Alexander W., Beckmann, Noam D., Schadt, Eric E., Abul-Husn, Noura S., Cho, Judy H., Itan, Yuval, Kenny, Eimear E., Loos, Ruth J. F., Nadkarni, Girish N., Do, Ron, O’Reilly, Paul, Huckins, Laura M., Ferreira, Manuel A. R., Abecasis, Goncalo R., Leader, Joseph B., Cantor, Michael N., Justice, Anne E., Carey, Dave J., Chittoor, Geetha, Josyula, Navya Shilpa, Kosmicki, Jack A., Horowitz, Julie E., Baras, Ari, Gass, Matthew C., Yadav, Ashish, Mirshahi, Tooraj, Hottenga, Jouke Jan, Bartels, Meike, de geus, Eco E. J. C., Nivard, Michel M. G., Verma, Anurag, Ritchie, Marylyn D., Rader, Daniel, Li, Binglan, Verma, Shefali S., Lucas, Anastasia, Bradford, Yuki, Abedalthagafi, Malak, Alaamery, Manal, Alshareef, Abdulraheem, Sawaji, Mona, Massadeh, Salam, AlMalik, Abdulaziz, Alqahtani, Saleh, Baraka, Dona, Harthi, Fawz Al, Alsolm, Ebtehal, Safieh, Leen Abu, Alowayn, Albandary M., Alqubaishi, Fatimah, Mutairi, Amal Al, Mangul, Serghei, Almutairi, Mansour, Aljawini, Nora, Albesher, Nour, Arabi, Yaseen M., Mahmoud, Ebrahim S., Khattab, Amin K., Halawani, Roaa T., Alahmadey, Ziab Z., Albakri, Jehad K., Felemban, Walaa A., Suliman, Bandar A., Hasanato, Rana, Al-Awdah, Laila, Alghamdi, Jahad, AlZahrani, Deema, AlJohani, Sameera, Al-Afghani, Hani, AlDhawi, Nouf, AlBardis, Hadeel, Alkwai, Sarah, Alswailm, Moneera, Almalki, Faisal, Albeladi, Maha, Almohammed, Iman, Barhoush, Eman, Albader, Anoud, Alotaibi, Sara, Alghamdi, Bader, Jung, Junghyun, fawzy, Mohammad S., Alrashed, May, Zeberg, Hugo, Nkambul, Lindo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Tardif, Nicola, Rooyackers, Olav, Grip, Jonathan, Maricic, Tomislav, Helgeland, Øyvind, Magnus, Per, Trogstad, Lill-Iren S., Lee, Yunsung, Harris, Jennifer R., Mangino, Massimo, Spector, Tim D., Emma, Duncan, Moutsianas, Louka, Caulfield, Mark J., Scott, Richard H., Kousathanas, Athanasio, Pasko, Dorota, Walker, Susan, Stuckey, Alex, Odhams, Christopher A., Rhodes, Daniel, Fowler, Tom, Rendon, Augusto, Chan, Georgia, Arumugam, Prabhu, Karczewski, Konrad J., Martin, Alicia R., Wilson, Daniel J., Spencer, Chris C. A., Crook, Derrick W., Wyllie, David H., O’Connell, Anne Marie, Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikola, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Seed, Cotton, Daly, Mark J., Finucane, Hilary, Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicola, Koelling, Nil, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, Cusick, Caroline, Soranzo, Nicole, Zhao, Jing Hua, Danesh, John, Angelantonio, Emanuele Di, Butterworth, Adam S., Sun, Yan V., Huffman, Jennifer E., Cho, Kelly, O’Donnell, Christopher J., Tsao, Phil, Gaziano, J. Michael, Peloso, Gina, Ho, Yuk-Lam, Smieszek, Sandra P., Polymeropoulos, Christo, Polymeropoulos, Vasilio, Polymeropoulos, Mihael H., Przychodzen, Bartlomiej P., Fernandez-Cadenas, Israel, Planas, Anna M., Perez-Tur, Jordi, Llucià-Carol, Laia, Cullell, Natalia, Muiño, Elena, Cárcel-Márquez, Jara, DeDiego, Marta L., Iglesias, Lara Lloret, Soriano, Alex, Rico, Veronica, Agüero, Daiana, Bedini, Josep L., Lozano, Francisco, Domingo, Carlo, Robles, Veronica, Ruiz-Jaén, Francisca, Márquez, Leonardo, Gomez, Juan, Coto, Eliecer, Albaiceta, Guillermo M., García-Clemente, Marta, Dalmau, David, Arranz, Maria J., Dietl, Beatriz, Serra-Llovich, Alex, Soler, Pere, Colobrán, Roger, Martín-Nalda, Andrea, Martínez, Alba Parra, Bernardo, David, Rojo, Silvia, Fiz-López, Aida, Arribas, Elisa, de la Cal-Sabater, Paloma, Segura, Tomá, González-Villa, Esther, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Jiménez-Xarrié, Elena, de Felipe Mimbrera, Alicia, Masjuan, Jaime, García-Madrona, Sebastian, Domínguez-Mayoral, Anna, Villalonga, Joan Montaner, Menéndez-Valladares, Paloma, Chasman, Daniel I., Sesso, Howard D., Manson, JoAnn E., Buring, Julie E., Ridker, Paul M., Franco, Giulianini, Davis, Lea, Lee, Sulggi, Priest, Jame, Sankaran, Vijay G., van Heel, David, Biesecker, Le, Kerchberger, V. Eric, Baillie, J. Kenneth, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Biological Psychology, APH - Mental Health, AMS - Sports, AMS - Ageing & Vitality, APH - Methodology, Mccurdy, Shannon, Mccormick, Joseph B., Macarthur, Daniel, Maclaughlin, Bev, Lefaive, Jonathon, Almalik, Abdulaziz, Alzahrani, Deema, Aljohani, Sameera, Aldhawi, Nouf, Albardis, Hadeel, Fawzy, Mohammad S., Dediego, Marta L., Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), University of Zurich, COVID-19 Host Genetics Initiative, Barcelona Supercomputing Center, COVID-19 Genetics Initiative, including authors, Institute for Molecular Medicine Finland, and Data Science Genetic Epidemiology Lab
Subjects: Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], Quantitative Trait Loci, MUC5B PROMOTER POLYMORPHISM, Genome-wide association studies, COVID-19 (Malaltia), UFSP13-7 Evolution in Action: From Genomes to Ecosystems, COVID-19 (Disease), Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, SDG 3 - Good Health and Well-being, Humans, genetics, Genetic variation, Genomes, Medicinsk genetik, 1000 Multidisciplinary, Multidisciplinary, Chromosome Mapping, COVID-19, Human Genetics, 10124 Institute of Molecular Life Sciences, covid-19, 3121 General medicine, internal medicine and other clinical medicine, 570 Life sciences, biology, Medical Genetics
Abstract: Matters arising from: Mapping the human genetic architecture of COVID-19 Original Article published on 08 July 2021 https://www.nature.com/articles/s41586-021-03767-x The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity. Here we present meta-analyses bringing together 60 studies from 25 countries (Fig. 1 and Supplementary Table 1) for three COVID-19-related phenotypes: (1) individuals critically ill with COVID-19 on the basis of requiring respiratory support in hospital or who died as a consequence of the disease (9,376 cases, of which 3,197 are new in this data release, and 1,776,645 control individuals); (2) individuals with moderate or severe COVID-19 defined as those hospitalized due to symptoms associated with the infection (25,027 cases, 11,386 new and 2,836,272 control individuals); and (3) all cases with reported SARS-CoV-2 infection regardless of symptoms (125,584 cases, 76,022 new and 2,575,347 control individuals). Most studies have reported results before the roll out of the COVID-19 vaccination campaign. An overview of the study design is provided in Supplementary Fig. 1. We found a total of 23 genome-wide significant loci (P
Published: 2022

22. Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative

Author: Guillaume, Butler-Laporte, Gundula, Povysil, Kosmicki, Jack A., Cirulli, Elizabeth T., Theodore, Drivas, Furini, Simone, Chadi, Saad, Axel, Schmidt, Pawel, Olszewski, Urszula, Korotko, Mathieu, Quinodoz, Elifnaz, Çelik, Kousik, Kundu, Klaudia, Walter, Junghyun, Jung, Stockwell, Amy D., Sloofman, Laura G., Jordan, Daniel M., Thompson, Ryan C., Diane Del Valle, Nicole, Simons, Esther, Cheng, Robert, Sebra, Schadt, Eric E., Seunghee, Kim-Schulze, Sacha, Gnjatic, Miriam, Merad, Buxbaum, Joseph D., Beckmann, Noam D., Charney, Alexander W., Bartlomiej, Przychodzen, Timothy, Chang, Pottinger, Tess D., Ning, Shang, Fabian, Brand, Fava, Francesca, Mari, Francesca, Karolina, Chwialkowska, Magdalena, Niemira, Szymon, Pula, J Kenneth Baillie, Alex, Stuckey, Antonio, Salas, Xabier, Bello, Jacobo, Pardo-Seco, Alberto, Gómez-Carballa, Irene, Rivero-Calle, Federico, Martinón-Torres, Andrea, Ganna, Karczewski, Konrad J., Kumar, Veerapen, Mathieu, Bourgey, Guillaume, Bourque, Robert JM Eveleigh, Vincenzo, Forgetta, David, Morrison, David, Langlais, Mark, Lathrop, Vincent, Mooser, Tomoko, Nakanishi, Robert, Frithiof, Michael, Hultström, Miklos, Lipcsey, Yanara, Marincevic-Zuniga, Jessica, Nordlund, Schiabor Barrett, Kelly M., William, Lee, Alexandre, Bolze, Simon, White, Stephen, Riffle, Francisco, Tanudjaja, Efren, Sandoval, Iva, Neveux, Shaun, Dabe, Nicolas, Casadei, Susanne, Motameny, Manal, Alaamery, Salam, Massadeh, Nora, Aljawini, Almutairi, Mansour S., Arabi, Yaseen M., Alqahtani, Saleh A., Al Harthi, Fawz S., Amal, Almutairi, Fatima, Alqubaishi, Sarah, Alotaibi, Albandari, Binowayn, Alsolm, Ebtehal A., Hadeel El Bardisy, Mohammad, Fawzy, Fang, Cai, Nicole, Soranzo, Adam, Butterworth, COVID-19 Host Genetics Initiative, DeCOI Host Genetics Group, GEN-COVID Multicenter Study (Italy), Daga, Sergio, Meloni, Ilaria, Mount Sinai Clinical Intelligence Center, GEN-COVID consortium (Spain), Genomicc, Consortium, Japan COVID-19 Task Force, Regeneron Genetics Center, Geschwind, Daniel H., Stephanie, Arteaga, Alexis, Stephens, Butte, Manish J., Boutros, Paul C., Yamaguchi, Takafumi N., Shu, Tao, Stefan, Eng, Timothy, Sanders, Tung, Paul J., Broudy, Michael E., Pan, Yu, Alfredo, Gonzalez, Nikhil, Chavan, Ruth, Johnson, Bogdan, Pasaniuc, Brian, Yaspan, Sandra, Smieszek, Carlo, Rivolta, Stephanie, Bibert, Pierre-Yves, Bochud, Maciej, Dabrowski, Pawel, Zawadzki, Mateusz, Sypniewski, Elżbieta, Kaja, Pajaree, Chariyavilaskul, Voraphoj, Nilaratanakul, Nattiya, Hirankarn, Vorasuk, Shotelersuk, Monnat, Pongpanich, Chureerat, Phokaew, Wanna, Chetruengchai, Katsushi, Tokunaga, Masaya, Sugiyama, Yosuke, Kawai, Takanori, Hasegawa, Tatsuhiko, Naito, Namkoong, Ho, Ryuya, Edahiro, Akinori, Kimura, Seishi, Ogawa, Takanori, Kanai, Koichi, Fukunaga, Yukinori, Okada, Seiya, Imoto, Satoru, Miyano, Serghei, Mangul, Abedalthagafi, Malak S., Hugo, Zeberg, Grzymski, Joseph J., Washington, Nicole L., Stephan, Ossowski, Ludwig, Kerstin U., Schulte, Eva C., Olaf, Riess, Marcin, Moniuszko, Miroslaw, Kwasniewski, Hamdi, Mbarek, Ismail, Said I., Anurag, Verma, Goldstein, David B., Krzysztof, Kiryluk, Renieri, Alessandra, Ferreira, Manuel A. R., J Brent Richards, Butler-Laporte, Guillaume, Povysil, Gundula, Kosmicki, Jack A, Cirulli, Elizabeth T, Drivas, Theodore, Furini, Simone, Saad, Chadi, Schmidt, Axel, Olszewski, Pawel, Korotko, Urszula, Quinodoz, Mathieu, Çelik, Elifnaz, Kundu, Kousik, Walter, Klaudia, Jung, Junghyun, Stockwell, Amy D, Sloofman, Laura G, Jordan, Daniel M, Thompson, Ryan C, Del Valle, Diane, Simons, Nicole, Cheng, Esther, Sebra, Robert, Schadt, Eric E, Kim-Schulze, Seunghee, Gnjatic, Sacha, Merad, Miriam, Buxbaum, Joseph D, Beckmann, Noam D, Charney, Alexander W, Przychodzen, Bartlomiej, Chang, Timothy, Pottinger, Tess D, Shang, Ning, Brand, Fabian, Fava, Francesca, Mari, Francesca, Chwialkowska, Karolina, Niemira, Magdalena, Pula, Szymon, Baillie, J Kenneth, Stuckey, Alex, Salas, Antonio, Bello, Xabier, Pardo-Seco, Jacobo, Gómez-Carballa, Alberto, Rivero-Calle, Irene, Martinón-Torres, Federico, Ganna, Andrea, Karczewski, Konrad J, Veerapen, Kumar, Bourgey, Mathieu, Bourque, Guillaume, Eveleigh, Robert Jm, Forgetta, Vincenzo, Morrison, David, Langlais, David, Lathrop, Mark, Mooser, Vincent, Nakanishi, Tomoko, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Marincevic-Zuniga, Yanara, Nordlund, Jessica, Schiabor Barrett, Kelly M, Lee, William, Bolze, Alexandre, White, Simon, Riffle, Stephen, Tanudjaja, Francisco, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Casadei, Nicola, Motameny, Susanne, Alaamery, Manal, Massadeh, Salam, Aljawini, Nora, Almutairi, Mansour S, Arabi, Yaseen M, Alqahtani, Saleh A, Al Harthi, Fawz S, Almutairi, Amal, Alqubaishi, Fatima, Alotaibi, Sarah, Binowayn, Albandari, Alsolm, Ebtehal A, El Bardisy, Hadeel, Fawzy, Mohammad, Cai, Fang, Soranzo, Nicole, Butterworth, Adam, Geschwind, Daniel H, Arteaga, Stephanie, Stephens, Alexi, Butte, Manish J, Boutros, Paul C, Yamaguchi, Takafumi N, Tao, Shu, Eng, Stefan, Sanders, Timothy, Tung, Paul J, Broudy, Michael E, Pan, Yu, Gonzalez, Alfredo, Chavan, Nikhil, Johnson, Ruth, Pasaniuc, Bogdan, Yaspan, Brian, Smieszek, Sandra, Rivolta, Carlo, Bibert, Stephanie, Bochud, Pierre-Yve, Dabrowski, Maciej, Zawadzki, Pawel, Sypniewski, Mateusz, Kaja, Elżbieta, Chariyavilaskul, Pajaree, Nilaratanakul, Voraphoj, Hirankarn, Nattiya, Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Tokunaga, Katsushi, Sugiyama, Masaya, Kawai, Yosuke, Hasegawa, Takanori, Naito, Tatsuhiko, Namkoong, Ho, Edahiro, Ryuya, Kimura, Akinori, Ogawa, Seishi, Kanai, Takanori, Fukunaga, Koichi, Okada, Yukinori, Imoto, Seiya, Miyano, Satoru, Mangul, Serghei, Abedalthagafi, Malak S, Zeberg, Hugo, Grzymski, Joseph J, Washington, Nicole L, Ossowski, Stephan, Ludwig, Kerstin U, Schulte, Eva C, Riess, Olaf, Moniuszko, Marcin, Kwasniewski, Miroslaw, Mbarek, Hamdi, Ismail, Said I, Verma, Anurag, Goldstein, David B, Kiryluk, Krzysztof, Renieri, Alessandra, Ferreira, Manuel A R, Richards, J Brent, Data Science Genetic Epidemiology Lab, Institute for Molecular Medicine Finland, University of Helsinki, and Helsinki Institute of Life Science HiLIFE
Subjects: Infectious Medicine, Cancer Research, Host genetics is a key determinant of COVID-19 outcomes. Previously, Infektionsmedicin, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights, Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, Genetics, Humans, Exome, Genetic Predisposition to Disease, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Medicinsk genetik, SARS-CoV-2, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, 1184 Genetics, developmental biology, physiology, COVID-19, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5, 737 controls, Toll-Like Receptor 7, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, 085 severe disease cases and 571, thereby informing therapeutics development. Here, Medical Genetics, Genome-Wide Association Study
Abstract: Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
Published: 2022

23. Mapping the human genetic architecture of COVID-19

Author: Niemi, MEK, Karjalainen, J, Liao, RG, Neale, BM, Daly, M, Ganna, A, Pathak, GA, Andrews, SJ, Kanai, M, Veerapen, K, Fernandez-Cadenas, I, Schulte, EC, Striano, P, Marttila, M, Minica, C, Marouli, E, Karim, MA, Wendt, FR, Savage, J, Sloofman, L, Butler-Laporte, G, Kim, H-N, Kanoni, S, Okada, Y, Byun, J, Han, Y, Uddin, MJ, Smith, GD, Willer, CJ, Buxbaum, JD, Mehtonen, J, Finucane, H, Cordioli, M, Martin, AR, Zhou, W, Pasaniuc, B, Julienne, H, Aschard, H, Shi, H, Yengo, L, Polimanti, R, Ghoussaini, M, Schwartzentruber, J, Dunham, I, Chwialkowska, K, Francescatto, M, Trankiem, A, Balaconis, MK, Davis, L, Lee, S, Priest, J, Renieri, A, Sankaran, VG, van Heel, D, Deelen, P, Richards, JB, Nakanishi, T, Biesecker, L, Kerchberger, VE, Kenneth, J, Mari, F, Bernasconi, A, Ceri, S, Canakoglu, A, Wolford, B, Faucon, A, Dutta, AK, Schurmann, C, Harry, E, Birney, E, Nguyen, H, Nasir, J, Kaunisto, M, Solomonson, M, Dueker, N, Vadgama, N, Limou, S, Rahmouni, S, Mbarek, H, Darwish, D, Uddin, MM, Albertos, R, Perez-Tur, J, Li, R, Folkersen, L, Moltke, I, Koelling, N, Teumer, A, Kousathanas, A, Utrilla, A, Verdugo, RA, Zarate, R, Medina-Gomez, C, Gomez-Cabrero, D, Carnero-Montoro, E, Cadilla, CL, Moreno-Estrada, A, Garmendia, A, Moya, L, Sedaghati-Khayat, B, Boua, PR, Fave, M-J, Francioli, L, Lemacon, A, Migeotte, I, Patel, S, Varnai, R, Szentpeteri, JL, Sipeky, C, Colombo, F, von Hohenstaufen, K, Lio, P, Vallerga, C, Wang, Q, Tanigawa, Y, Im, H, Han, C, Song, H, Lim, J, Lee, Y, Kim, S, Im, S, Atanasovska, B, Ahmad, HF, Boer, C, Jansen, P, Franke, L, Kaja, E, Pasko, D, Kennis-Szilagyi, I, Kornilov, SA, Prijatelj, V, Prokic, I, Sivanadhan, I, Perumal, S, Esmaeeli, S, Pearson, NM, Auton, A, Shelton, JF, Shastri, AJ, Filshtein-Sonmez, T, Coker, D, Symons, A, Esparza-Gordillo, J, Aslibekyan, S, O'Connell, J, Ye, C, Weldon, CH, Perera, M, O'Leary, K, Tuck, M, O'Brien, T, Meltzer, D, O'Donnell, P, Nutescu, E, Yang, G, Alarcon, C, Herrmann, S, Mazurek, S, Banagan, J, Hamidi, Z, Barbour, A, Raffat, N, Moreno, D, Friedman, P, Ferwerda, B, van de Beek, D, Brouwer, MC, Vlaar, APJ, Wiersinga, WJ, Posthuma, D, Tissink, E, Zwinderman, AHK, Uffelmann, E, van Agtmael, M, Algera, AG, van Baarle, F, Bax, D, Beudel, M, Bogaard, HJ, Bomers, M, Bonta, PI, Bos, L, Botta, M, de Brabander, J, de Bree, G, de Bruin, S, Bugiani, M, Bulle, E, Chouchane, O, Cloherty, A, Dongelmans, D, Elbers, P, Fleuren, L, Geerlings, S, Geerts, B, Geijtenbeek, T, Girbes, A, Goorhuis, B, Grobusch, MP, Hafkamp, F, Hagens, L, Hamann, J, Harris, V, Hemke, R, Hermans, SM, Heunks, L, Hollmann, M, Horn, J, Hovius, JW, de Jong, MD, Koning, R, van Mourik, N, Nellen, J, Nossent, EJ, Paulus, F, Peters, E, van der Poll, T, Preckel, B, Prins, JM, Raasveld, J, Reijnders, T, Schinkel, M, Schultz, MJ, Schuurman, A, Sigaloff, K, Smit, M, Stijnis, CS, Stilma, W, Teunissen, C, Thoral, P, Tsonas, A, van der Valk, M, Veelo, D, de Vries, H, van Vugt, M, Wouters, D, Minnaar, RP, Kromhout, A, van Uffelen, KWJ, Wolterman, RA, Roberts, G, Park, D, Ball, CA, Coignet, M, McCurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Hong, EL, Rand, K, Girshick, A, Guturu, H, Baltzell, AH, Guntz, J, Beguin, Y, Pigazzini, S, Nkambule, L, Bouysran, Y, Busson, A, Peyrassol, X, Wilkin, F, Pichon, B, Smits, G, Vandernoot, I, Goffard, J-C, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Jadot, L, Azarzar, S, Dellot, P, Gofflot, S, Claassen, S, Bertrand, A, Parzibut, G, Clarinval, M, Moermans, C, Malaise, O, El Kandoussi, K, Thonon, R, Huynen, P, Mesdagh, A, Melo, S, Jacques, N, Di Valentin, E, Giroule, F, Collignon, A, Radermecker, C, Lebrun, M, Peree, H, Latour, S, Barada, O, Sanchez, J, Josse, C, Boujemla, B, Meunier, M, Mariavelle, E, Anania, S, Gazon, H, Juszczak, D, Fadeur, M, Camby, S, Meuris, C, Thys, M, Jacques, J, Henket, M, Leonard, P, Frippiat, F, Giot, J-B, Sauvage, A-S, Von Frenckell, C, Mni, M, Wery, M, Staderoli, A, Belhaj, Y, Lambermont, B, Morrison, DR, Mooser, V, Forgetta, V, Ghosh, B, Laurent, L, Belisle, A, Henry, D, Abdullah, T, Adeleye, O, Mamlouk, N, Kimchi, N, Afrasiabi, Z, Rezk, N, Vulesevic, B, Bouab, M, Guzman, C, Petitjean, L, Tselios, C, Xue, X, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Brassard, N, Durand, M, Schurr, E, Lepage, P, Ragoussis, J, Auld, D, Chasse, M, Kaufmann, DE, Lathrop, GM, Adra, D, Davis, LK, Cox, NJ, Below, JE, Sealock, JM, Faucon, AB, Shuey, MM, Polikowsky, HG, Petty, LE, Shaw, DM, Chen, H-H, Zhu, W, Ludwig, KU, Schroeder, J, Maj, C, Rolker, S, Noethen, MM, Fazaal, J, Keitel, V, Jensen, B-EO, Feldt, T, Kurth, I, Marx, N, Dreher, M, Pink, I, Cornberg, M, Illig, T, Lehmann, C, Schommers, P, Augustin, M, Rybniker, J, Knopp, L, Eggermann, T, Volland, S, Altmueller, J, Berger, MM, Brenner, T, Hinney, A, Witzke, O, Bals, R, Herr, C, Ludwig, N, Walter, J, Fuchsberger, C, Pattaro, C, De Grandi, A, Pramstaller, P, Emmert, D, Melotti, R, Foco, L, Mascalzoni, D, Gogele, M, 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Mandalà, Marco, Zucchi, Patrizia, Giannattasio, Ferdinando, Coviello, Domenico A., Mussini, Cristina, Bosio, Giancarlo, Tavecchia, Luisa, Crotti, Lia, Rizzi, Marco, La Rovere, Maria Teresa, Sarzi-Braga, Simona, Bussotti, Maurizio, Ravaglia, Sabrina, Artuso, Rosangela, Perrella, Antonio, Romani, Davide, Bergomi, Paola, Catena, Emanuele, Vincenti, Antonella, Ferri, Claudio, Grassi, Davide, Pessina, Gloria, Tumbarello, Mario, Di Pietro, Massimo, Sabrina, Ravaglia, Luchi, Sauro, Barbieri, Chiara, Acquilini, Donatella, Andreucci, Elena, Paciosi, Francesco, Segala, Francesco Vladimiro, Tiseo, Giusy, Falcone, Marco, Lista, Mirjam, Poscente, Monica, De Vivo, Oreste, Petrocelli, Paola, Guarnaccia, Alessandra, Baroni, Silvia, Perticaroli, Valentina, Furini, Simone, Dei, Simona, Benetti, Elisa, Picchiotti, Nicola, Sanarico, Maurizio, Ceri, Stefano, Pinoli, Pietro, Raimondi, Francesco, Biscarini, Filippo, Stella, Alessandra, Bergomi, Mattia, Zguro, Kristina, Capitani, Katia, Tanfoni, Marco, 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Eunsoon, Jang, Hye Yoon, Kim, Sunmie, Kym, Sungmin, Kim, Yeon-Sook, Jeong, Hyeongseok, Kwon, Ki Tae, Kim, Shin-Woo, Kim, Jin Yong, Jang, Young Rock, Kim, Hyun ah, Lee, Ji Yeon, Lee, Jeong Eun, Lee, Shinwon, Choe, Kang-Won, Kang, Yu Min, Jee, Sun Ha, Jung, Keum Ji, Parikh, Victoria, Ashley, Euan, Wheeler, Matthew, Rivas, Manuel, Bustamante, Carlo, Pinksy, Benjamin, Febbo, Phillip, Farh, Kyle, Schroth, Gary P., Desouza, Franci, Dalton, Karen, Christle, Jeff, Deboever, Christopher, Szalma, Sándor, Rubinacci, Simone, Delaneau, Olivier, Gorzynski, John, de Jong, Hannah, Sutton, Shirley, Youlton, Nathan, Joshi, Ruchi, Jimenez-Morales, David, Hughes, Christopher, Amar, David, Ioannidis, Alex, Hershman, Steve, Kirillova, Anna, Seo, Kinya, Huang, Yong, Shoura, Massa, Hammond, Nathan, Watson, Nathaniel, Raja, Archana, Huang, Chunhong, Sahoo, Malaya, Wang, Hannah, Zhen, Jimmy, Rakitko, Alexander, Ilinsky, Valery, Yermakovich, Danat, Popov, Iaroslav, Chernitsov, Alexander, Kovalenko, Elena, Krasnenko, Anna, Plotnikov, Nikolay, Stetsenko, Ivan, Kim, Anna, Cirulli, Elizabeth T., Schiabor Barrett, Kelly M., Bolze, Alexandre, White, Simon, Washington, Nicole L., Lu, James T., Riffle, Stephen, Tanudjaja, Francisco, Wang, Xueqing, Ramirez, Jimmy M., Leonetti, Nicole, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Grzymski, Joseph J., Esteban Miñano, Juan Ignacio, Aguirre, Luis A., López-Collazo, Eduardo, de la Mata Pazos, Manuel, Cerrato, Luciano, Lozano-Rodríguez, Roberto, Avendaño-Ortiz, José, Arcos, Verónica Terrón, Montalbán-Hernández, Karla Marina, Quiroga, Jaime Valentín, Pascual-Iglesias, Alejandro, Maroun-Eid, Charbel, Martín-Quirós, Alejandro, Namkoong, Ho, Imoto, Seiya, Katayama, Kazuhiko, Fukunaga, Koichi, Kitagawa, Yuko, Sato, Toshiro, Hasegawa, Naoki, Kumanogoh, Atsushi, Kimura, Akinori, Ai, Masumi, Tokunaga, Katsushi, Kanai, Takanori, Miyano, Satoru, Ogawa, Seishi, Edahiro, Ryuya, Sonehara, Kyuto, Shirai, Yuya, Ishii, Makoto, Kabata, Hiroki, Masaki, Katsunori, Kamata, Hirofumi, Ikemura, Shinnosuke, Chubachi, Shotaro, Okamori, Satoshi, Terai, Hideki, Tanaka, Hiromu, Morita, Atsuho, Lee, Ho, Asakura, Takanori, Sasaki, Junichi, Morisaki, Hiroshi, Uwamino, Yoshifumi, Nanki, Kosaku, Mikami, Yohei, Tomono, Kazunori, Kato, Kazuto, Matsuda, Fumihiko, Takahashi, Meiko, Hizawa, Nobuyuki, Takeda, Yoshito, Hirata, Haruhiko, Shiroyama, Takayuki, Miyawaki, Satoru, Suzuki, Ken, Maeda, Yuichi, Nii, Takuro, Noda, Yoshimi, Niitsu, Takayuki, Adachi, Yuichi, Enomoto, Takatoshi, Amiya, Saori, Hara, Reina, Takahashi, Kunihiko, Anzai, Tatsuhiko, Hasegawa, Takanori, Ito, Satoshi, Koike, Ryuji, Endo, Akifumi, Uchimura, Yuji, Miyazaki, Yasunari, Honda, Takayuki, Tateishi, Tomoya, Tohda, Shuji, Ichimura, Naoya, Sonobe, Kazunari, Sassa, Chihiro, Nakajima, Jun, Nannya, Yasuhito, Omae, Yosuke, Takahashi, Kazuhisa, Harada, Norihiro, Hiki, Makoto, Takagi, Haruhi, Nakamura, Ai, Tagaya, Etsuko, Kawana, Masatoshi, Arimura, Ken, Ishiguro, Takashi, Takayanagi, Noboru, Isono, Taisuke, Takaku, Yotaro, Takano, Kenji, Anan, Ryusuke, Nakajima, Yukiko, Nakano, Yasushi, Nishio, Kazumi, Ueda, Soichiro, Hayashi, Reina, Tateno, Hiroki, Hase, Isano, Yoshida, Shuichi, Suzuki, Shoji, Mitamura, Keiko, Saito, Fumitake, Ueda, Tetsuya, Azuma, Masanori, Nagasaki, Tadao, Yasui, Yoshinori, Hasegawa, Yoshinori, Mutoh, Yoshikazu, Yoshiyama, Takashi, Shoko, Tomohisa, Kojima, Mitsuaki, Adachi, Tomohiro, Ishikawa, Motonao, Takahashi, Kenichiro, Watanabe, Kazuyoshi, Manabe, Tadashi, Ito, Fumimaro, Fukui, Takahiro, Funatsu, Yohei, Koh, Hidefumi, Hirai, Yoshihiro, Kawashima, Hidetoshi, Narita, Atsuya, Niwa, Kazuki, Sekikawa, Yoshiyuki, Saito, Fukuki, Yoshiya, Kazuhisa, Yoshihara, Tomoyuki, Suzuki, Yusuke, Nakayama, Sohei, Masuzawa, Keita, Nishi, Koichi, Nishitsuji, Masaru, Tani, Maiko, Inoue, Takashi, Hirano, Toshiyuki, Kobayashi, Keigo, Miyazawa, Naoki, Kimura, Yasuhiro, Sado, Reiko, Ogura, Takashi, Kitamura, Hideya, Murohashi, Kota, Nakachi, Ichiro, Baba, Rie, Arai, Daisuke, Fuke, Satoshi, Saito, Hiroshi, Kuwahara, Naota, Fujiwara, Akiko, Okada, Takenori, Baba, Tomoya, Noda, Junya, Mashimo, Shuko, Yagi, Kazuma, Shiomi, Tetsuya, Hashiguchi, Mizuha, Odani, Toshio, Mochimaru, Takao, Oyamada, Yoshitaka, Mori, Nobuaki, Izumi, Namiki, Nagata, Kaoru, Taki, Reiko, Murakami, Koji, Yamada, Mitsuhiro, Sugiura, Hisatoshi, Hayashi, Kentaro, Shimizu, Tetsuo, Gon, Yasuhiro, Fujitani, Shigeki, Tsuchida, Tomoya, Yoshida, Toru, Kagaya, Takashi, Kita, Toshiyuki, Sakagami, Satoru, Kimizuka, Yoshifumi, Kawana, Akihiko, Nakamura, Yoshihiko, Ishikura, Hiroyasu, Takata, Tohru, Kikuchi, Takahide, Taniyama, Daisuke, Nakamura, Morio, Kodama, Nobuhiro, Kaneyama, Yasunari, Maeda, Shunsuke, Nagasaki, Yoji, Okamoto, Masaki, Ishihara, Sayoko, Ito, Akihiro, Chihara, Yusuke, Takeuchi, Mayumi, Onoi, Keisuke, Hashimoto, Naozumi, Wakahara, Keiko, Ando, Akira, Masuda, Makoto, Wakabayashi, Aya, Watanabe, Hiroki, Sageshima, Hisako, Nakada, Taka-Aki, Abe, Ryuzo, Shimada, Tadanaga, Kawamura, Kodai, Ichikado, Kazuya, Nishiyama, Kenta, Yamasaki, Masaki, Hashimoto, Satoru, Kusaka, Yu, Ohba, Takehiko, Isogai, Susumu, Takada, Minoru, Kanda, Hidenori, Komase, Yuko, Sano, Fumiaki, Asano, Koichiro, Oguma, Tsuyoshi, Harada, Masahiro, Takahashi, Takeshi, Shibusawa, Takayuki, Abe, Shinji, Kono, Yuta, Togashi, Yuki, Izumo, Takehiro, Inomata, Minoru, Awano, Nobuyasu, Ogawa, Shinichi, Ogata, Tomouki, Ishihara, Shoichiro, Kanehiro, Arihiko, Ozaki, Shinji, Fuchimoto, Yasuko, Kitagawa, Yuichiro, Yoshida, Shozo, Ogura, Shinji, Nishiyama, Kei, Yoshida, Kousuke, Beppu, Satoru, Fukuyama, Satoru, Eriguchi, Yoshihiro, Yonekawa, Akiko, Inoue, Yoshiaki, Yamagata, Kunihiro, Chiba, Shigeru, Narumoto, Osamu, Nagai, Hideaki, Ooshima, Nobuharu, Motegi, Mitsuru, Sagara, Hironori, Tanaka, Akihiko, Ohta, Shin, Shibata, Yoko, Tanino, Yoshinori, Sato, Yuki, Yamada, Yuichiro, Hashino, Takuya, Shinoki, Masato, Iwagoe, Hajime, Imamura, Tomonori, Umeda, Akira, Shimada, Hisato, Endo, Mayu, Hayashi, Shinichi, Takahashi, Mai, Nakano, Shigefumi, Yatomi, Masakiyo, Maeno, Toshitaka, Ishii, Tomoo, Utsugi, Mitsuyoshi, Ono, Akihiro, Kanaoka, Kensuke, Ihara, Shoichi, Komuta, Kiyoshi, Boezen, Marike, Claringbould, Annique, Lopera, Esteban, Warmerdam, Robert, Vonk, Judith. M., van Blokland, Irene, Lanting, Pauline, Ori, Anil P. S., Obeidat, Ma’En, Hernández Cordero, Ana I., Sin, Don D., Bossé, Yohan, Joubert, Philippe, Hao, Ke, Nickle, David, Timens, Wim, van den Berge, Maarten, Feng, Yen-Chen Anne, Mercader, Josep, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Green, Robert C., Perez, Emma F., Zöllner, Sebastian, Wang, Jiongming, Beck, Andrew, Sloofman, Laura G., Ascolillo, Steven, Sebra, Robert P., Collins, Brett L., Levy, Te, Sealfon, Stuart C., Jordan, Daniel M., Thompson, Ryan C., Gettler, Kyle, Chaudhary, Kumardeep, Belbin, Gillian M., Preuss, Michael, Hoggart, Clive, Choi, Sam, Underwood, Slayton J., Salib, Irene, Britvan, Bari, Keller, Katherine, Tang, Lara, Peruggia, Michael, Hiester, Liam L., Niblo, Kristi, Aksentijevich, Alexandra, Labkowsky, Alexander, Karp, Avromie, Zlatopolsky, Menachem, Zyndorf, Marissa, Charney, Alexander W., Beckmann, Noam D., Schadt, Eric E., Abul-Husn, Noura S., Cho, Judy H., Itan, Yuval, Kenny, Eimear E., Loos, Ruth J. F., Nadkarni, Girish N., Do, Ron, O’Reilly, Paul, Huckins, Laura M., Ferreira, Manuel A. R., Abecasis, Goncalo R., Leader, Joseph B., Cantor, Michael N., Justice, Anne E., Carey, Dave J., Chittoor, Geetha, Josyula, Navya Shilpa, Kosmicki, Jack A., Horowitz, Julie E., Baras, Ari, Gass, Matthew C., Yadav, Ashish, Mirshahi, Tooraj, Jan Hottenga, Jouke, Bartels, Meike, de Geus, Eco J. C., Nivard, Michel G., Verma, Anurag, Ritchie, Marylyn D., Rader, Daniel, Li, Binglan, Verma, Shefali S., Lucas, Anastasia, Bradford, Yuki, Zara, Federico, Salpietro, Vincenzo, Scala, Marcello, Iacomino, Michele, Scudieri, Paolo, Bocciardi, Renata, Minetti, Carlo, Riva, Antonella, Vari, Maria Stella, Rahier, Jean-Françoi, Giorgio, Elisa, Carli, Diana, Louis, Edouad, Bulik, Cynthia M., Landén, Mikael, Brusco, Alfredo, Ferrero, Giovanni Battista, Madia, Francesca, Fundín, Bengt, Ismail, Said I., Saad, Chadi, Al-Sarraj, Yaser, Badji, Radja Messai, Al-Muftah, Wadha, Al Thani, Asma, Afifi, Nahla, Klovins, Jani, Rovite, Vita, Rescenko, Raimond, Peculis, Raiti, Ustinova, Monta, Zeberg, Hugo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Johnson, Ruth, Geschwind, Daniel H., Freimer, Nelson, Butte, Manish J., Ding, Yi, Chiu, Alec, Chang, Timothy S., Boutros, Paul, Moutsianas, Louka, Caulfield, Mark J., Scott, Richard H., Walker, Susan, Stuckey, Alex, Odhams, Christopher A., Rhodes, Daniel, Fowler, Tom, Rendon, Augusto, Chan, Georgia, Arumugam, Prabhu, Karczewski, Konrad J., Wilson, Daniel J., Spencer, Chris A., Crook, Derrick W., Wyllie, David H., O’Connell, Anne Marie, Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikola, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Seed, Cotton, Daly, Mark J., Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicola, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, Cusick, Caroline, Soranzo, Nicole, Zhao, Jing Hua, Danesh, John, Di Angelantonio, Emanuele, Butterworth, Adam S., Sun, Yan V., Huffman, Jennifer E., Cho, Kelly, O’Donnell, Christopher J., Tsao, Phil, Gaziano, J. Michael, Peloso, Gina, Ho, Yuk-Lam, Mian, Michael, Scaggiante, Federica, Chang, Xiao, Glessner, Joseph R., Hakonarson, Hakon, Mcguigan, Peter J., Prockter Moore, Luke Stephen, Vizcaychipi, Marcela Paola, Hall, Kathryn, Campbell, Andy, Nichol, Ailstair, Ward, Geraldine, Page, Valerie Joan, Semple, Malcolm G., Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Aldera, Erin L., Alegria, Ana, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nichola, Bassford, Christopher, Basude, Sneha, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Best, Nicola, Bothma, Pieter, Chadwick, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chri, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, Drummond, Andrew, Durand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Christopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B., Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tama, Lillie, Patrick, Limb, Jame, Linnett, Vanessa, Little, Jeff, Lyttle, Mark, Macmahon, Michael, Macnaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, Mccullough, Katherine, Mcewen, Ruth, Meda, Manjula, Mills, Gary H., Minton, Jane, Ward, Karl, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, Jame, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapa, Nelson, Mark, O’Shea, Matthew K., Otahal, Igor, Ostermann, Marlie, Pais, Mark, Panchatsharam, Selva, Papakonstantinou, Danai, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Pooni, Jagtur Singh, Post, Frank, Price, David, Prout, Rachel, Rae, Nikola, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ryan, Brendan, Saluja, Taranprit, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tama, Tatham, Kate, Thomas, Jo, Thompson, Chri, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Ustianowski, Andrew, Vallotton, Nick, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Papineni, Padmasayee, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Cole, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wooton, Daniel G., Workman, Andrew, Yates, Bryan, Young, Peter, Beale, Rupert, Bretherick, Andrew D., Clohisey, Sara, Fourman, Max Head, Furniss, Jame, Gountouna, Elvina, Grimes, Graeme, Haley, Chri, Harrison, David, Hayward, Caroline, Keating, Sean, Klaric, Lucija, Klenerman, Paul, Law, Andy, Meynert, Alison M., Millar, Jonathan, Pairo-Castineira, Erola, Parkinson, Nichola, Ponting, Chris P., Porteous, David J., Rawlik, Konrad, Richmond, Anne, Rowan, Kathy, Russell, Clark D., Shen, Xia, Shih, Barbara, Tenesa, Albert, Vitart, Veronique, Wang, Bo, Wilson, James F., Wu, Yang, Yang, Jian, Yang, Zhijian, Zechner, Marie, Zhai, Ranran, Zheng, Chenqing, Norman, Lisa, Pius, Riinu, Drake, Thomas M., Fairfield, Cameron J., Knight, Stephen R., Mclean, Kenneth A., Murphy, Derek, Shaw, Catherine A., Dalton, Jo, Girvan, Michelle, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Leeming, Gary, Law, Andrew, Wham, Murray, Hendry, Ro, Scott-Brown, Jame, Begg, Colin, Hinds, Charle, Wai Ho, Antonia Ying, Horby, Peter W., Knight, Julian, Ling, Lowell, Maslove, David, Mcauley, Danny, Montgomery, Hugh, Nichol, Alistair, Openshaw, Peter J. M., Summers, Charlotte, Walsh, Timothy, Armstrong, Lisa, Bates, Hayley, Dooks, Emma, Farquhar, Fiona, Hairsine, Brigid, Mcparland, C., Packham, Sophie, Alldis, Zoe, Astin-Chamberlain, Raine, Bibi, Fatima, Biddle, Jack, Blow, Sarah, Bolton, Matthew, Borra, Catherine, Bowles, Ruth, Burton, Maudrian, Choudhury, Yasmin, Collier, David, Cox, Amber, Easthope, Amy, Ebano, Patrizia, Fotiadis, Stavro, Gurasashvili, Jana, Halls, Rosslyn, Hartridge, Pippa, Kallon, Delordson, Kassam, Jamila, Lancoma-Malcolm, Ivone, Matharu, Maninderpal, May, Peter, Mitchelmore, Oliver, Newman, Tabitha, Patel, Mital, Pheby, Jane, Pinzuti, Irene, Prime, Zoe, Prysyazhna, Oleksandra, Shiel, Julian, Taylor, Melanie, Tierney, Carey, Wood, Suzanne, Zak, Anne, Zongo, Olivier, Forsey, Miranda, Nicholson, Anne, Riches, Joanne, Vertue, Mark, Wasson, Christopher, Finn, Stephanie, Green, Jackie, Collins, Erin, King, Bernadette, Grauslyte, Lina, Hussain, Musarat, Pogreban, Tatiana, Rosaroso, Lace, Salciute, Erika, Franke, George, Wong, Joanna, George, Aparna, Akeroyd, Louise, Bano, Shereen, Bromley, Matt, Gurr, Lucy, Lawton, Tom, Morgan, Jame, Sellick, Kirsten, Warren, Deborah, Wilkinson, Brian, Mcgowan, Janet, Ledgard, Camilla, Stacey, Amelia, Pye, Kate, Bellwood, Ruth, Bentley, Michael, Loosley, Ronda, Mcguinness, Heather, Tench, Helen, Wolf-Roberts, Rebecca, Gibson, Sian, Lyle, Amanda, Mcneela, Fiona, Radhakrishnan, Jayachandran, Hughes, Alistair, Ali, Asifa, Brady, Megan, Dale, Sam, Dance, Annalisa, Gledhill, Lisa, Greig, Jill, Hanson, Kathryn, Holdroyd, Kelly, Home, Marie, Kelly, Diane, Kitson, Ro, Matapure, Lear, Melia, Deborah, Mellor, Samantha, Nortcliffe, Tonicha, Pinnell, Jez, Robinson, Matthew, Shaw, Lisa, Shaw, Ryan, Thomis, Lesley, Wilson, Alison, Wood, Tracy, Bayo, Lee-Ann, Merwaha, Ekta, Ishaq, Tahira, Hanley, Sarah, Antcliffe, David, Banach, Dorota, Brett, Stephen, Coghlan, Phoebe, Fernandez, Ziortza, Gordon, Anthony, Rojo, Roceld, Arias, Sonia Sousa, Templeton, Maie, Jha, Rajeev, Krishnamurthy, Vinodh, Lim, Lai, Bi, Rehana, Scholefield, Barney, Ashton, Lydia, Williams, Alison, Cheyne, Claire, Saunderson, Anne, Allan, Angela, Anderson, Felicity, Kaye, Callum, Liew, Jade, Medhora, Jasmine, Scott, Teresa, Trumper, Erin, Botello, Adriana, Polgarova, Petra, Stroud, Katerina, Meaney, Eoghan, Jones, Megan, Ng, Anthony, Agrawal, Shruti, Pathan, Nazima, White, Deborah, Daubney, Esther, Elston, Kay, Parker, Robert, Reddy, Amie, Turner-Bone, Ian, Wilding, Laura, Harding, Peter, Jacob, Reni, Jones, Cathy, Denmade, Craig, Croft, Maria, White, Ian, Lim, Li, Griffin, Denise, Muchenje, Nycola, Mupudzi, Mcdonald, Partridge, Richard, Conyngham, Jo-Anna, Thomas, Rachel, Wright, Mary, Corral, Maria Alvarez, Bastion, Victoria, Clarke, Daphene, David, Beena, Kent, Harriet, Lorusso, Rachel, Lubimbi, Gamu, Murdoch, Sophie, Penacerrada, Melchizedek, Thomas, Alastair, Valentine, Jennifer, Vochin, Ana, Wulandari, Retno, Djeugam, Brice, Dawson, Joy, Garrioch, Sweyn, Tolson, Melanie, Aldridge, Jonathan, de Almeida Martins, Laura Gome, Carungcong, Jaime, Beavis, Sarah, Dale, Katie, Gascoyne, Rachel, Hawes, Joanne, Pritchard, Kelly, Stevenson, Lesley, Whileman, Amanda, Cowley, Anne, Highgate, Judith, Crawley, Rikki, Crew, Abigail, Cunningham, Mishell, Daniels, Allison, Harrison, Laura, Hope, Susan, Inweregbu, Ken, Jones, Sian, Lancaster, Nicola, Matthews, Jamie, Nicholson, Alice, Wray, Gemma, Benham, Leonie, Bradshaw, Zena, Brown, Joanna, Caswell, Melanie, Melling, Sarah, Preston, Stephen, Slawson, Nicola, Stoddard, Emma, Warden, Scott, Combes, Edward, Joefield, Teishel, Monnery, Sonja, Beech, Valerie, Trotman, Sallyanne, Hopkins, Bridget, Scriven, Jame, Thrasyvoulou, Laura, Willis, Heather, Anderson, Susan, Birch, Janine, Collins, Emma, Hammerton, Kate, O’Leary, Ryan, Abernathy, Caroline, Foster, Louise, Gratrix, Andrew, Martinson, Vicky, Parkinson, Priyai, Stones, Elizabeth, Carbral-Ortega, Llucia, Kapoor, Ritoo, Loader, David, Castle, Karen, Brandwood, Craig, Smith, Lara, Clark, Richard, Birchall, Katie, Kolakaluri, Laurel, Baines, Deborah, Sukumaran, Anila, Mapfunde, Isheunesu, Meredith, Megan, Morris, Lucy, Ryan, Lucy, Clark, Amy, Sampson, Julia, Peters, Cecilia, Dent, Martin, Langley, Margaret, Ashraf, Saima, Wei, Shuying, Andrew, Angela, Chablani, Manish, Kirkby, Amy, Netherton, Kimberley, Bates, Michelle, Dasgin, Jo, Gill, Jaspret, Nilsson, Annette, Apetri, Elena, Basikolo, Cathrine, Blackledge, Bethan, Catlow, Laura, Charles, Bethan, Doonan, Reece, Harris, Jade, Harvey, Alice, Horner, Daniel, Knowles, Karen, Lee, Stephanie, Lomas, Diane, Lyons, Chloe, Marsden, Tracy, Mclaughlan, Danielle, Mcmorrow, Liam, Pendlebury, Jessica, Perez, Jane, Poulaka, Maria, Proudfoot, Nicola, Slaughter, Melanie, Slevin, Kathryn, Thomas, Vicky, Walker, Danielle, Michael, Angiy, Collis, Matthew, Clark, Martyn, Coulding, Martina, Jude, Edward, Mccormick, Jacqueline, Mercer, Oliver, Potla, Darsh, Rehman, Hafiz, Savill, Heather, Turner, Victoria, Davey, Miriam, Golden, David, Seaman, Rebecca, Hunt, Jodie, Dearden, Joy, Dobson, Emma, Mulcahy, Michelle, Munt, Sheila, O’Connor, Grainne, Philbin, Jennifer, Rishton, Chloe, Tully, Redmond, Winnard, Sarah, Cagova, Lenka, Fofano, Adama, Garner, Lucie, Holcombe, Helen, Mepham, Sue, Mitchell, Alice Michael, Mwaura, Lucy, Praman, K., Vuylsteke, Alain, Zamikula, Julie, Bercades, Georgia, Brealey, David, Hass, Ingrid, Maccallum, Niall, Martir, Glady, Raith, Eamon, Reyes, Anna, Smyth, Deborah, Taylor, Abigail, Hughes, Rachel Anne, Thomas, Helen, Rees, Alun, Duskova, Michaela, Phipps, Janet, Brooks, Suzanne, Edwards, Michelle, Alexander, Peter, Allen, Schvearn, Bradley-Potts, Joanne, Brantwood, Craig, Egan, Jasmine, Felton, Timothy, Padden, Grace, Ward, Luke, Moss, Stuart, Glasgow, Susannah, Beesley, Kate, Board, Sarah, Kubisz-Pudelko, Agnieszka, Lewis, Alison, Perry, Je, Pippard, Lucy, Wood, Di, Buckley, Clare, Brown, Alison, Gregory, Jane, O’Connell, Susan, Smith, Tim, Belagodu, Zakaula, Fuller, Bridget, Gherman, Anca, Olufuwa, Olumide, Paramsothy, Remi, Stuart, Carmel, Oakley, Naomi, Kamundi, Charlotte, Tyl, David, Collins, Katy, Silva, Pedro, Taylor, June, King, Laura, Coates, Charlotte, Crowley, Maria, Wakefield, Phillipa, Beadle, Jane, Johnson, Laura, Sargeant, Janet, Anderson, Madeleine, Jardine, Catherine, Williams, Dewi, Parris, Victoria, Quaid, Sheena, Watson, Ekaterina, Melville, Julie, Naisbitt, Jay, Joseph, Rosane, Lazo, Maria, Walton, Olivia, Neal, Alan, Hill, Michaela, Kannan, Thogulava, Wild, Laura, Allan, Elizabeth, Darlington, Kate, Davies, Ffyon, Easton, Jack, Kumar, Sumit, Lean, Richard, Menzies, Daniel, Pugh, Richard, Qiu, Xinyi, Davies, Llino, Williams, Hannah, Scanlon, Jeremy, Davies, Gwyneth, Mackay, Callum, Lewis, Joannne, Rees, Stephanie, Coetzee, Samantha, Gales, Alistair, Raj, Meena, Sell, Craig, Langton, Helen, Watters, Malcolm, Novis, Catherine, Arbane, Gill, Bociek, Aneta, Campos, Sara, Grau, Neu, Jones, Tim Owen, Lim, Rosario, Marotti, Martina, Whitton, Christopher, Barron, Anthony, Collins, Ciara, Kaul, Sundeep, Passmore, Heather, Prendergast, Claire, Reed, Anna, Rogers, Paula, Shokkar, Rajvinder, Woodruff, Meriel, Middleton, Hayley, Polgar, Oliver, Nolan, Claire, Thwaites, Vicky, Mahay, Kanta, Sri-Chandana, Chunda, Scherewode, Joslan, Stephenson, Lorraine, Marsh, Sarah, Bancroft, Hollie, Bellamy, Mary, Carmody, Margaret, Daglish, Jacqueline, Moore, Faye, Rhodes, Joanne, Sangombe, Mirriam, Kadiri, Salma, Ayers, Amanda, Harrison, Wendy, North, Julie, Cavazza, Anna, Cockrell, Maeve, Corcoran, Eleanor, Depante, Maria, Finney, Clare, Jerome, Ellen, Mcphail, Mark, Nayak, Monalisa, Noble, Harriet, O’Reilly, Kevin, Pappa, Evita, Saha, Rohit, Saha, Sian, Smith, John, Knighton, Abigail, Gill, Mandy, Paul, Paul, Ratnam, Valli, Shelton, Sarah, Wynter, Inez, Baptista, David, Crowe, Rebecca, Fernandes, Rita, Herdman-Grant, Rosaleen, Joseph, Anna, Loveridge, Adam, Mckenley, India, Morino, Eriko, Naranjo, Andre, Simms, Richard, Sollesta, Kathryn, Swain, Andrew, Venkatesh, Harish, Khera, Jacyntha, Fox, Jonathan, Barber, Russell, Hewitt, Claire, Hilldrith, Annette, Jackson-Lawrence, Karen, Shepardson, Sarah, Wills, Maryanne, Butler, Susan, Tavares, Silvia, Cunningham, Amy, Hindale, Julia, Arif, Sarwat, George, Linsha, Twiss, Sophie, Wright, David, Holland, Maureen, Keenan, Natalie, Lyons, Marc, Wassall, Helen, Marsh, Chri, Mahenthran, Mervin, Carter, Emma, Kong, Thoma, Adanini, Oluronke, Bhatia, Nikhil, Msiska, Maine, Mew, Louise, Mwaura, Esther, Williams, Felicity, Wren, Lynn, Sutherland, Sara-Beth, Battle, Ceri, Brinkworth, Elaine, Harford, Rachel, Murphy, Carl, Newey, Luke, Rees, Tabitha, Williams, Marie, Arnold, Sophie, Hardy, John, Houlden, Henry, Moncur, Eleanor, Tariq, Ambreen, Tucci, Arianna, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Keshet-Price, Jocelyn, Randell, Georgina, Stammers, Katie, Abdelrazik, Marwa, Bakthavatsalam, Dhanalakshmi, Elhassan, Munzir, Ganesan, Arunkumar, Haldeos, Anne, Moreno-Cuesta, Jeronimo, Purohit, Dharam, Vincent, Rachel, Xavier, Kugan, Rohit, Kumar, Alasdair, Frater, Saleem, Malik, David, Carter, Jenkins, Samuel, Lamond, Zoe, Wall, Alanna, Reynolds, Jessica, Campbell, Helen, Thompsom, Maria, Dodds, Steve, Duffy, Stacey, Butcher, Deborah, O’Sullivan, Susie, Butterworth-Cowin, Nicola, Deacon, Bethan, Hibbert, Meg, Pothecary, Carla, Tetla, Dariusz, Woodford, Christopher, Durga, Latha, Kennard-Holden, Gareth, de Gordoa, Laura Ortiz-Ruiz, Peasgood, Emily, Phillips, Claire, Skinner, Denise, Gaylard, Jane, Mullan, Dee, Newman, Julie, Davies, Ellie, Roche, Lisa, Sathe, Sonia, Brimfield, Lutece, Daly, Zoe, Pogson, David, Rose, Steve, Collins, Amy, Khaliq, Waqa, Gude, Estefania Treu, Allen, Louise, Beranova, Eva, Crisp, Nikki, Deery, Joanne, Hazelton, Tracy, Knight, Alicia, Price, Carly, Tilbey, Sorrell, Turki, Salah, Turney, Sharon, Giles, Julian, Booth, Simon, Bell, Gillian, English, Katy, Katary, Amro, Wilcox, Louise, Campbell, Rachael, Clarke, Noreen, Whiteside, Jonathan, Mascarenhas, Mairi, Donaldson, Avril, Matheson, Joanna, Barrett, Fiona, O’Hara, Marianne, O’Keefe, Laura, Bradley, Clare, Collier, Dawn, Walker, Rachel, Maynard, Victoria, Patel, Tahera, Smith, Matthew, Kazi, Aayesha, Hartley, Janice, Dykes, Joseph, Hijazi, Muhammad, Keith, Sarah, Khan, Meherunnisa, Ryan-Smith, Janet, Springle, Philippa, Thomas, Jacqueline, Truman, Nick, Saad, Samuel, Coleman, Dabheoc, Fine, Christopher, Matt, Roseanna, Gay, Bethan, Dalziel, Jack, Ali, Syamlan, Goodchild, Drew, Harling, Rhiannan, Bhatterjee, Ravi, Goddard, Wendy, Davison, Chloe, Duberly, Stephen, Hargreaves, Jeanette, Bolton, Rachel, Verlander, Mark, Williams, Alexandra, Blackman, Helen, Creagh-Brown, Ben, Donlon, Sinead, Michalak-Glinska, Natalia, Mtuwa, Sheila, Pristopan, Veronika, Salberg, Armorel, Smith, Eleanor, Stone, Sarah, Piercy, Charle, Verula, Jerik, Burda, Dorota, Montaser, Rugia, Harden, Lesley, Mayangao, Irving, Marriott, Cheryl, Bradley, Paul, Harris, Celia, Cooper, Joshua, Finch, Cheryl, Liderth, Sarah, Quinn, Alison, Waddington, Natalia, Fidler, Katy, Tagliavini, Emma, Donnelly, Kevin, Abel, Lynn, Brett, Michael, Digby, Brian, Gemmell, Lisa, Hornsby, Jame, Macgoey, Patrick, O’Neil, Pauline, Price, Richard, Rodden, Natalie, Rooney, Kevin, Sundaram, Radha, Thomson, Nicola, Flanagan, Rebecca, Hughes, Gareth, Latham, Scott, Mckenna, Emma, Anderson, Jennifer, Hull, Robert, Rhead, Kat, Branney, Debbie, Frankham, Jordan, Pitts, Sally, White, Nigel, Cristiano, Daniele, Dormand, Natalie, Farzad, Zohreh, Gummadi, Mahitha, Liyanage, Kamal, Patel, Brijesh V., Salmi, Sara, Sloane, Geraldine, Varghese, Mathew, Zborowski, Anelise C., Bean, Sarah, Burt, Karen, Spivey, Michael, Eastgate-Jackson, Christine, Filipe, Helder, Martin, Daniel, Maharajh, Amitaa, Garcia, Sara Mingo, De Neef, Mark, Lynch, Ceri, Howe, Gwenllian Sera, Singh, Jayaprakash, Turner, Keri, Ellis, Hannah, Stroud, Natalie, Cherian, Shiney, Cutler, Sean, Heron, Anne Emma, Roynon-Reed, Anna, Williams, Gemma, Richards, Owen, Cheema, Yusuf, Ahmad, Norfaizan, Barker, Joann, Bauchmuller, Kri, Bird, Sarah, Cawthron, Kay, Harrington, Kate, Jackson, Yvonne, Kibutu, Faith, Lenagh, Becky, Masuko, Shamiso, Raithatha, Ajay, Wiles, Matthew, Willson, Jayne, Newell, Helen, Lye, Alison, Nwafor, Lorenza, Jarman, Claire, Rowland-Jones, Sarah, Foote, David, Cole, Joby, Thompson, Roger, Watson, Jame, Hesseldon, Lisa, Macharia, Irene, Chetam, Luke, Smith, Jacqui, Ford, Amber, Anderson, Samantha, Birchall, Kathryn, Housley, Kay, Walker, Sara, Milner, Leanne, Hanratty, Helena, Trower, Helen, Phillips, Patrick, Oxspring, Simon, Donne, Ben, Bevan, Emily, Martin, Jane, Trodd, Dawn, Watson, Geoff, Brown, Caroline Wrey, Bunni, Lara, Jennings, Claire, Latif, Monica, Marshall, Rebecca, Subramanian, Gayathri, Bandla, Nageswar, Gellamucho, Minnie, Davies, Michelle, Thompson, Christopher, Trim, Fiona, Eapen, Beena, Ahmed, Cecilia, Baines, Balvinder, Clamp, Sarah, Colley, Julie, Haq, Risna, Hayes, Anne, Hulme, Jonathan, Hussain, Samia, Joseph, Sibet, Kumar, Rita, Maqsood, Zahira, Purewal, Manjit, Chandler, Ben, Elliott, Kerry, Mallinson, Janine, Turnbull, Alison, Dent, Kathy, Horsley, Elizabeth, Akhtar, Muhmmad Nauman, Pearson, Sandra, Potoczna, Dorota, Spencer, Sue, Blakemore, Hayley, Borislavova, Borislava, Faulkner, Beverley, Gendall, Emma, Goff, Elizabeth, Hayes, Kati, Thomas, Matt, Worner, Ruth, Smith, Kerry, Stephens, Deanna, Delgado, Carlos Castro, Dawson, Deborah, Ding, Lijun, Durrant, Georgia, Ezeobu, Obiageri, Farnell-Ward, Sarah, Harrison, Abiola, Kanu, Rebecca, Leaver, Susannah, Maccacari, Elena, Manna, Soumendu, Saluzzio, Romina Peperman, Queiroz, Joana, Samakomva, Tinashe, Sicat, Christine, Texeira, Joana, Da Gloria, Edna Fernande, Lisboa, Ana, Rawlins, John, Mathew, Jisha, Kinch, Ashley, Hurt, William Jame, Shah, Nirav, Clark, Victoria, Thanasi, Maria, Yun, Nikki, Patel, Kamal, Crickmore, Vikki, Debreceni, Gabor, Wilkins, Joy, Nicol, Liz, Burn, Iona, Hambrook, Geraldine, Manso, Katarina, Penn, Ruth, Shanmugasundaram, Pradeep, Tebbutt, Julie, Thornton, Danielle, Rostron, Anthony, Roy, Alistair, Woods, Lindsey, Cornell, Sarah, Wakinshaw, Fiona, Rogerson, Kimberley, Jarmain, Jordan, Anderson, Peter, Archer, Katie, Austin, Karen, Davis, Caroline, Durie, Alison, Kelsall, Olivia, Thrush, Jessica, Vigurs, Charlie, Wood, Hannah-Louise, Tranter, Helen, Harrison, Alison, Cowley, Nichola, Mcalindon, Michael, Digby, Stephen, Low, Emma, Morgan, Aled, Cother, Naiara, Rankin, Tobia, Clayton, Sarah, Mccurdy, Alex, Allibone, Suzanne, Mary-Genetu, Roman, Patel, Amit, Mac, Ainhi, Murphy, Anthony, Mahjoob, Parisa, Nazari, Roonak, Worsley, Lucy, Fagan, Andrew, Mohamed Ali, Inthakab Ali, Beaumont, Karen, Blunt, Mark, Coton, Zoe, Curgenven, Hollie, Elsaadany, Mohamed, Fernandes, Kay, Ally, Sameena Mohamed, Rangarajan, Harini, Sarathy, Varun, Selvanayagam, Sivarupan, Vedage, Dave, White, Matthew, Fernandez-Roman, Jaime, Hamilton, David O., Johnson, Emily, Johnston, Brian, Martinez, Maria Lopez, Mulla, Suleman, Shaw, David, Waite, Alicia A. C., Waugh, Victoria, Welters, Ingeborg D., Williams, Karen, Bemand, Thoma, Black, Ethel, Rosa, Arnold Dela, Howle, Ryan, Jhanji, Shaman, Baikady, Ravishankar Rao, Tatham, Kate Colette, Thomas, Benjamin, Halkes, Matthew, Mercer, Pauline, Thornton, Lorraine, West, Joe, Baird, Tracy, Ruddy, Jim, Reece-Anthony, Rosie, Birt, Mark, Cowton, Amanda, Kay, Andrea, Kent, Melanie, Potts, Kathryn, Wilkinson, Ami, Naylor, Suzanne, Brown, Ellen, Clark, Michele, Purvis, Sarah, Cole, Jade, Davies, Rhy, Duffin, Donna, Hill, Helen, Player, Ben, Thomas, Emma, Williams, Angharad, Beith, Claire Marie, Black, Karen, Clements, Suzanne, Morrison, Alan, Strachan, Dominic, Taylor, Margaret, Clarkson, Michelle, D’Sylva, Stuart, Norman, Kathryn, Coventry, Tina, Fowler, Susan, Mcgregor, Amanda, Brady, Ailbhe, Chan, Rebekah, Mcivor, Shane, Prady, Helena, Whittle, Helen, Mathew, Bijoy, Clapham, Melanie, Harper, Rosemary, Poultney, Una, Rice, Polly, Mutch, Rachel, Baird, Yolanda, Butler, Aaron, Chadbourn, Indra, Folkes, Linda, Fox, Heather, Gardner, Amy, Gomez, Raquel, Hobden, Gillian, King, Kirsten, Margarson, Michael, Martindale, Tim, Meadows, Emma, Raynard, Dana, Thirlwall, Yvette, Helm, David, Margalef, Jordi, Greer, Sandra, Shuker, Karen, Smuts, Sara, Duffield, Joseph, Smith, Oliver, Mallon, Lewi, Claire, Watkin, Birkinshaw, Isobel, Carter, Joseph, Howard, Kate, Ingham, Joanne, Joy, Rosie, Pearson, Harriet, Roche, Samantha, Scott, Zoe, Knights, Ellen, Price, Alicia, Thomas, Alice, Thorpe, Chri, Abraheem, Azmerelda, Bamford, Peter, Cawley, Kathryn, Dunmore, Charlie, Faulkner, Maria, Girach, Rumanah, Jeffrey, Helen, Jones, Rhianna, London, Emily, Nagra, Imrun, Nasir, Farah, Sainsbury, Hannah, Smedley, Clare, Khade, Reena, Sundar, Ashok, Tsinaslanidis, George, Behan, Teresa, Burnett, Caroline, Hatton, Jonathan, Heeney, Elaine, Mitra, Atideb, Newton, Maria, Pollard, Rachel, Stead, Rachael, Birch, Jenny, Bough, Laura, Goodsell, Josie, Tutton, Rebecca, Williams, Patricia, Williams, Sarah, Winter-Goodwin, Barbara, Auld, Fiona, Donnachie, Joanne, Edmond, Ian, Prentice, Lynn, Runciman, Nikole, Salutous, Dario, Symon, Lesley, Todd, Anne, Turner, Patricia, Short, Abigail, Sweeney, Laura, Murdoch, Euan, Senaratne, Dhaneesha, Burns, Karen, Higham, Andrew, Anderson, Taya, Hawcutt, Dan, O’Malley, Laura, Rad, Laura, Rogers, Naomi, Saunderson, Paula, Allison, Kathryn Sian, Afolabi, Deborah, Whitbread, Jennifer, Jones, Dawn, Dore, Rachael, Lankester, Liana, Nikitas, Nikita, Wells, Colin, Stowe, Bethan, Spencer, Kayleigh, Cathcart, Susanne, Duffy, Katharine, Puxty, Alex, Puxty, Kathryn, Turner, Lynne, Ireland, Jane, Semple, Gary, Barry, Peter, Hilltout, Paula, Evitts, Jayne, Tyler, Amanda, Waldron, Joanne, Irvine, Val, Shelley, Benjamin, Akinkugbe, Olugbenga, Bamford, Alasdair, Beech, Emily, Belfield, Holly, Bell, Michael, Davies, Charlene, Jones, Gareth A. L., Mchugh, Tara, Meghari, Hamza, O’Neill, Lauran, Peters, Mark J., Ray, Samiran, Tomas, Ana Luisa, Gorman, Claire, Gupta, Abhinav, Timlick, Elizabeth, Brady, Rebecca, Bonner, Stephen, Hugill, Keith, Jones, Jessica, Liggett, Steven, Bashyal, Archana, Davidson, Neil, Hutton, Paula, Mckechnie, Stuart, Wilson, Jean, Flint, Neil, Rekha, Patel, Hales, Dawn, Cruz, Carina, Gopal, Shameer, Harris, Nichola, Lake, Victoria, Metherell, Stella, Radford, Elizabeth, Clement, Ian, Patel, Bijal, Gulati, A., Hays, Carole, Webster, K., Hudson, Anne, Webster, Andrea, Stephenson, Elaine, Mccormack, Louise, Slater, Victoria, Nixon, Rachel, Hanson, Helen, Fearby, Maggie, Kelly, Sinead, Bridgett, Victoria, Robinson, Philip, Almaden-Boyle, Christine, Austin, Pauline, Cabrelli, Louise, Cole, Stephen, Casey, Matt, Chapman, Susan, Whyte, Clare, Brayne, Adam, Fisher, Emma, Hunt, Jane, Jackson, Peter, Kaye, Duncan, Love, Nichola, Parkin, Juliet, Tuckey, Victoria, van Koutrik, Lynne, Carter, Sasha, Andrew, Benedict, Findlay, Louise, Adams, Katie, Bruce, Michelle, Connolly, Karen, Duncan, Tracy, T. -Michael, Helen, Lindergard, Gabriella, Hey, Samuel, Fox, Claire, Alfonso, Jordan, Durrans, Laura Jayne, Guerin, Jacinta, Hruska, Martin, Eltayeb, Ayaa, Lamb, Thoma, Hodgkiss, Tracey, Cooper, Lisa, Rothwell, Joanne, Dennis, Catherine, Mcgregor, Alastair, Srikaran, Sinduya, Sukha, Anisha, Davies, Kim, O’Brien, Linda, Omar, Zohra, Perkins, Emma, Lewis, Tracy, Sutherland, Isobel, Brooke, Hollie, Buckley, Sarah, Suarez, Jose Cebrian, Charlesworth, Ruth, Hansson, Karen, Norris, John, Poole, Alice, Rose, Alastair, Sandhu, Rajdeep, Sloan, Brendan, Smithson, Elizabeth, Thirumaran, Muthu, Wagstaff, Veronica, Metcalfe, Alexandra, Camsooksai, Julie, Humphrey, Charlotte, Jenkins, Sarah, Wadams, Beverley, Death, Yasmin, Adams, Colene, Agasou, Anita, Arden, Tracie, Bowes, Amy, Boyle, Pauline, Beekes, Mandy, Button, Heather, Capps, Nigel, Carnahan, Mandy, Carter, Anne, Childs, Danielle, Donaldson, Denise, Hard, Kelly, Hurford, Fran, Hussain, Yasmin, Javaid, Ayesha, Jones, Jame, Jose, Sanal, Leigh, Michael, Martin, Terry, Millward, Helen, Motherwell, Nichola, Rikunenko, Rachel, Stickley, Jo, Summers, Julie, Ting, Louise, Tivenan, Helen, Tonks, Louise, Wilcox, Rebecca, Bokhari, Maria, Lucas, Rachael, Mccormick, Wendy, Ritzema, Jenny, Sanderson, Amanda, Wild, Helen, Baxter, Nicola, Henderson, Steven, Kennedy-Hay, Sophie, Mcparland, Christopher, Rooney, Laura, Sim, Malcolm, Mccreath, Gordan, Brunton, Mark, Caterson, Je, Coles, Holly, Frise, Matthew, Rai, Sabi Gurung, Keating, Liza, Tilney, Emma, Bartley, Shauna, Bhuie, Parminder, Downes, Charlotte, Holding, Kathleen, Riches, Katie, Hilton, Mary, Hayman, Mel, Subramanian, Deepak, Daniel, Priya, Zitter, Letizia, Benyon, Sarah, Marriott, Suzie, Park, Linda, Keenan, Samantha, Gordon, Elizabeth, Quinn, Helen, Baines, Kizzy, Andrew, Gillian, Barclay, Lucy, Callaghan, Marie, Clark, Sarah, Hope, Dave, Marshall, Lucy, Mcculloch, Corrienne, Briton, Kate, Singleton, Jo, Birch, Sophie, Simpson, Kerry, Craig, Jayne, Demetriou, Carrie, Eckbad, Charlotte, Hierons, Sarah, Howie, Lucy, Mitchard, Sarah, Ramos, Lidia, Serrano-Ruiz, Alfredo, White, Katie, Kelly, Fiona, Amin, Vishal, Anastasescu, Elena, Anumakonda, Vikram, Karthik, Komala, Kausar, Rizwana, Reid, Karen, Smith, Jacqueline, Imeson-Wood, Janet, Bellini, Arianna, Bryant, Jade, Mayer, Anton, Pickard, Amy, Roe, Nichola, Sowter, Jason, Howlett, Alex, Criste, Kristine, Cusack, Rebecca, Golder, Kim, Golding, Hannah, Jones, Oliver, Leggett, Samantha, Male, Michelle, Marani, Martyna, Prager, Kirsty, Williams, Toran, Roberts, Belinda, Salmon, Karen, Gondo, Prisca, Hadebe, B., Kayani, Abdul, Masunda, Bridgett, Ahmed, Ashar, Morris, Anna, Jakkula, Sriniva, Long, Kate, Whiteley, Simon, Wilby, Elizabeth, Ogg, Bethan, Moultrie, Sam, Odam, M., Bewley, Jeremy, Garland, Zoe, Grimmer, Lisa, Gumbrill, Bethany, Johnson, Rebekah, Sweet, Katie, Webster, Denise, Efford, Georgia, Bennett, Sara, Goodwin, Emma, Jackson, Matthew, Kent, Alissa, Tibke, Clare, Woodyatt, Wiesia, Zaki, Ahmed, Daniel, Amelia, Finn, Joanne, Saha, Rajnish, Bremmer, Pamela, Allan, J., Geary, T., Houston, Gordon, Meikle, A., O’Brien, P., Bell, Dina, Boyle, Rosalind, Douglas, Katie, Glass, Lynn, Lee, Emma, Lennon, Liz, Rattray, Austin, Charnock, Rob, Mcfarland, Denise, Cosgrove, Denise, Attwood, Ben, Parsons, Penny, Carmody, Siobhain, Oblak, Metod, Popescu, Monica, Thankachen, Mini, Baruah, Rosie, Morris, Sheila, Ferguson, Susie, Shepherd, Amy, Altabaibeh, Abdelhakim, Alvaro, Ana, Gilbert, Kayleigh, Ma, Louise, Mostoles, Loreta, Parmar, Chetan, Simpson, Kathryn, Jetha, Champa, Booker, Lauren, Pratley, Anezka, Cosier, Tracey, Millen, Gemma, Schumacher, Natasha, Weston, Heather, Rand, Jame, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S., Bogaert, Debby, Chand, Meera, Cooke, Graham S., Docherty, Annemarie B., Dunning, Jake, da Silva Filipe, Ana, Fletcher, Tom, Green, Christoper A., Harrison, Ewen M., Hiscox, Julian A., Ijaz, Samreen, Khoo, Saye, Lim, Wei Shen, Mentzer, Alexander J., Merson, Laura, Noursadeghi, Mahdad, Moore, Shona C., Palmarini, Massimo, Paxton, William A., Pollakis, Georgio, Price, Nichola, Rambaut, Andrew, Robertson, David L., Sancho-Shimizu, Vanessa, Scott, Janet T., de Silva, Thushan, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Tedder, Richard S., Thomson, Emma C., Roger Thompson, A. A., Thwaites, Ryan S., Turtle, Lance C. W., Gupta, Rishi K., Palmieri, Carlo, Swann, Olivia V., Zambon, Maria, Dumas, Marc-Emmanuel, Griffin, Julian L., Takats, Zoltan, Chechi, Kanta, Andrikopoulos, Petro, Osagie, Anthonia, Olanipekun, Michael, Liggi, Sonia, Lewis, Matthew R., Correia, Gonçalo dos Santo, Sands, Caroline J., Takis, Panteleimon, Maslen, Lynn, Greenhalf, William, Shaw, Victoria, Mcdonald, Sarah E., Keating, Seán, Ahmed, Katie A., Armstrong, Jane A., Ashworth, Milton, Asiimwe, Innocent G., Bakshi, Siddharth, Barlow, Samantha L., Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin W. A., Clark, Jordan J., Clarke, Emily A., Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chri, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis W. S., Foster, Terry, Garcia-Dorival, Isabel, Gunning, Philip, Hartley, Catherine, Jensen, Rebecca L., Jones, Christopher B., Jones, Trevor R., Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A., Mancini, Maria, Mcdonald, Sarah, Mcevoy, Laurence, Mclauchlan, John, Metelmann, Soeren, Miah, Nahida S., Middleton, Joanna, Mitchell, Joyce, Murphy, Ellen G., Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E., Shears, Rebecca K., Small, Benjamin, Subramaniam, Krishanthi S., Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Flaherty, Lisa, Maziere, Nicole, Cass, Emily, Carracedo, Alejandra Doce, Carlucci, Nicola, Holmes, Anthony, Massey, Hannah, Murphy, Lee, Wrobel, Nicola, Mccafferty, Sarah, Morrice, Kirstie, Maclean, Alan, Armstrong, Ruth, Boz, Ceilia, Brown, Adam, Coutts, Audrey, Cullum, Louise, Day, Nicky, Donnelly, Lorna, Duncan, Esther, Fawkes, Angie, Finernan, Paul, Gilchrist, Tammy, Golightly, Ailsa, Hafezi, Katarzyna, Law, Dawn, Law, Rachel, Law, Sarah, Macgillivray, Louise, Mal, Hanning, Mcmaster, Ellie, Meikle, Jen, Oosthuyzen, Wilna, Paterson, Trevor, Stenhouse, Andrew, Swets, Maaike, Szoor-McElhinney, Helen, Taneski, Filip, Wackett, Tony, Ward, Mairi, Weaver, Jane, Coyle, Judy, Gallagher, Bernadette, Lidstone-Scott, Rebecca, Hamilton, Debbie, Schon, Katherine, Furlong, Anita, Biggs, Heather, Griffiths, Fiona, Andrews, Eleanor, Brickell, Kathy, Smyth, Michelle, Murphy, Lorna, Carson, Gail, Hardwick, Hayley, Donohue, Chloe, Pérez-Tur, Jordi [0000-0002-9111-1712], Martín, Javier [0000-0002-2202-0622], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts General Hospital [Boston], A list of authors and their affiliations appears in the Supplementary Information, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-21-COVR-0039,GenMIS-C,Recherche 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[0000-0003-1513-6077], Apollo - University of Cambridge Repository, Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Guided Treatment in Optimal Selected Cancer Patients (GUTS), AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, Graduate School, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Niemi, M. E. K., Liao, R. G., Neale, B. M., Pathak, G. A., Andrews, S. J., Schulte, E. C., Karim, M. A., Wendt, F. 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E., Sealock, J. M., Faucon, A. B., Shuey, M. M., Polikowsky, H. G., Petty, L. E., Shaw, D. M., Chen, H. -H., Ludwig, K. U., Schroder, J., Nothen, M. M., Jensen, B. -E. O., Altmuller, J., Berger, M. M., Gogele, M., Gignoux, C. R., Wicks, S. J., Barnes, K. C., Goldstein, D. B., Reilly, M. P., Gharavi, A. G., O'Byrne, S. M., So, Y. S., Park, S. -K., Kim, H. -L., Kang, C. K., Lee, H. -J., Song, K. -H., Yoon, K. J., Paik, N. -J., Joo, E. -J., Park, W. B., Park, J. S., Park, K. U., Ham, S. Y., Kim, E. S., Kim, H. B., Caceres, M., Lenz, T. L., Julia, A., Holter, J. C., Fernandez, J., Sander, L. E., Banales, J. M., Romero-Gomez, M., Hov, J. R., Karlsen, T. H., Wacker, E. M., Elabd, H., Ruhlemann, M. C., Vadla, M. S., Lenning, O. B., Ozer, O., Kassens, J., Figuera Basso, M. E., Ortiz, A. B., Chercoles, A. G., Holten, A. R., Kildal, A. B., Gluck, A., Nolla, A. C., Dyrhol-Riise, A. M., Spinner, C. D., Hoff, D. A. L., Jimenez, D., Pestana, D., Helbig, E. T., Paraboschi, E. M., Sanchez, F. G., Hernandez, I., Galvan-Femenia, I., Badia, J. R., Muller, K. E., Gaede, K. I., Lippert, L. J., Tellez, L., Gutierrez-Stampa, M. A., Vehreschild, M. J. G. T., Marquie, M., Seilmaier, M. J., Rodriguez-Gandia, M., Ayo, N. I., Martinez, N., Cornely, O. A., Rodrigues, P. M., Espana, P. P., Garcia-Fernandez, A. -E., Fracanzani, A. L., Muniz-Diaz, E., Calderon, E. J., Solligard, E., Medrano, F. J., Muller, F., Afset, J. E., Damas, J. K., Ferrusquia-Acosta, J., Quero, J. H., Guerrero, J. M., Bettini, L. R., Gustad, L. T., Valsecchi, M. G., D'Angio, M., Gallego-Duran, R., Cejudo, T. G., Grimsrud, M. M., Gudbjartsson, D. F., Moore, K. H. S., Alarcon-Riquelme, M. E., Martinez-Bueno, M., Rello, S. R., Lall, K., Bochud, P. -Y., Nussle, S. G., Meyer zu Bentrup, F., Merlet Viollet, R., Guery, B., Hugli, O., Gonseth Nussle, S., Estoppey Younes, S., Rochat Negro, T., Mercader, J. M., Castano-Vinyals, G., Dobano, C., Mondelli, M. U., Mazzei, M. A., Caldarelli, G. P., Monforte, A. D., Scotton, P. G., Monica, M. D., Mandala, M., Coviello, D. A., La Rovere, M. T., Segala, F. V., Mencarelli, M. A., Pinto, A. M., Carriero, M. L., Ann Belli, M., Antoni, M. D., Miraglia, F. G., Parisi, S. G., Squeo, G. M., Botta, G., Hunt, K. A., Trembath, R. C., Martin, H. C., Griffiths, C. J., Curtis, C. J., Huang, Q. Q., Lee, S. H., Macarthur, D., Maclaughlin, B., Smith, A. V., Boughton, A. P., Li, K. W., Lefaive, J., Jannes, C. E., Krieger, J. E., Pereira, A. C., Lima, I. R., Tada, M. T., Mccarthy, M., Lee, J. E., Lee, H. S., Jang, H. Y., Kim, Y. -S., Kwon, K. T., Kim, S. -W., Kim, J. Y., Jang, Y. R., Kim, H., Lee, J. Y., Choe, K. -W., Kang, Y. M., Jee, S. H., Jung, K. J., Schroth, G. P., Desouza, F., Cirulli, E. T., Schiabor Barrett, K. M., Washington, N. L., Lu, J. T., Ramirez, J. M., Grzymski, J. J., Minano, J. I. E., Aguirre, L. A., Lopez-Collazo, E., Lozano-Rodriguez, R., Avendano-Ortiz, J., Arcos, V. T., Montalban-Hernandez, K. M., Quiroga, J. V., Martin-Quiros, A., Nakada, T. -A., Vonk, J. M., Ori, A. P. S., Hernandez Cordero, A. I., Sin, D. D., Bosse, Y., Feng, Y. -C. A., Weiss, S. T., Karlson, E. W., Smoller, J. W., Murphy, S. N., Meigs, J. B., Woolley, A. E., Green, R. C., Perez, E. F., Zollner, S., Sloofman, L. G., Sebra, R. P., Collins, B. L., Sealfon, S. C., Jordan, D. M., Thompson, R. C., Belbin, G. M., Underwood, S. J., Hiester, L. L., Charney, A. W., Beckmann, N. D., Schadt, E. E., Abul-Husn, N. S., Cho, J. H., Kenny, E. E., Loos, R. J. F., Nadkarni, G. N., Huckins, L. M., Ferreira, M. A. R., Abecasis, G. R., Leader, J. B., Cantor, M. N., Justice, A. E., Carey, D. J., Josyula, N. S., Kosmicki, J. A., Horowitz, J. E., Gass, M. C., Hottenga, J. J., de Geus, E. J. C., Nivard, M. G., Ritchie, M. D., Verma, S. S., Vari, M. S., Rahier, J. -F., Bulik, C. M., Landen, M., Ferrero, G. B., Fundin, B., Ismail, S. I., Badji, R. M., Hultstrom, M., Geschwind, D. H., Butte, M. J., Chang, T. S., Caulfield, M. J., Scott, R. 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A., de Almeida Martins, L. G., Mclaughlan, D., Mcmorrow, L., Mccormick, J., Mitchell, A. M., Maccallum, N., Hughes, R. A., Jones, T. O., Mcphail, M., Mckenley, I., Sutherland, S. -B., de Gordoa, L. O. -R., Gude, E. T., Macgoey, P., Mckenna, E., Patel, B. V., Zborowski, A. C., Garcia, S. M., Howe, G. S., Heron, A. E., Mills, G. H., Brown, C. W., Akhtar, M. N., Delgado, C. C., Saluzzio, R. P., Da Gloria, E. F., Hurt, W. J., Wood, H. -L., Mcalindon, M., Mccurdy, A., Ali, I. A. M., Ally, S. M., Hamilton, D. O., Lopez Martinez, M., Waite, A. A. C., Welters, I. D., Rosa, A. D., Baikady, R. R., Tatham, K. C., Beith, C. M., Mcgregor, A., Mcivor, S., Allison, K. S., Jones, G. A. L., Mchugh, T., Peters, M. J., Tomas, A. L., Mckechnie, S., Mccormack, L., Michael, H. T., Durrans, L. J., Suarez, J. C., Death, Y., Mccormick, W., Mccreath, G., Rai, S. G., Mcculloch, C., Mcfarland, D., Barclay, W. S., Cooke, G. S., Docherty, A. B., Green, C. A., Harrison, E. M., Hiscox, J. A., Lim, W. S., Mentzer, A. J., Paxton, W. A., Robertson, D. L., Scott, J. T., Tedder, R. S., Thomson, E. C., Thwaites, R. S., Gupta, R. K., Swann, O. V., Dumas, M. -E., Griffin, J. L., Lewis, M. R., dos Santos Correia, G., Sands, C. J., Mcdonald, S. E., Ahmed, K. A., Armstrong, J. A., Asiimwe, I. G., Barlow, S. L., Catterall, B. W. A., Clark, J. J., Clarke, E. A., Fisher, L. W. S., Jensen, R. L., Jones, C. B., Jones, T. R., Kiy, R. T., Livoti, L. A., Mcdonald, S., Mcevoy, L., Mclauchlan, J., Miah, N. S., Moore, S. C., Murphy, E. G., Matthew Ridley, P., Shaw, V. E., Shears, R. K., Subramaniam, K. S., Eunice Zhang, J., Carracedo, A. D., Mccafferty, S., Turtle, L. C. W., Data Science Genetic Epidemiology Lab, Institute for Molecular Medicine Finland, HUS Helsinki and Uusimaa Hospital District, University of Helsinki, Research Programs Unit, Doctoral Programme in Population Health, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, and University of Zurich
Subjects: Male, 45/43, Autoimmunity, Autoimmunity/genetics, Body Mass Index, COVID-19/genetics, COVID-19/virology, Critical Illness, Female, Genetic Loci/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Geographic Mapping, Hospitalization, Host-Pathogen Interactions/genetics, Humans, Inflammation/complications, Information Dissemination, Multifactorial Inheritance, Racial Groups/genetics, SARS-CoV-2/pathogenicity, Smoking, environmental risk factors, Q1, 631/208, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genetics, Genome-wide association studies, SARS-CoV-2, Viral infection, GWAS, Aetiology, Lung, QC, 0303 health sciences, HERITABILITY, 3. Good health, covid-19, Science & Technology - Other Topics, Identification (biology), Infection, Human, 631/208/205/2138, Settore BIO/11 - Biologia Molecolare, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Clinical Research, Biodefense, Genetics, GENOME-WIDE ASSOCIATION, Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714 [VDP], METAANALYSIS, 1000 Multidisciplinary, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, Prevention, Racial Groups, Pneumonia, genetic architecture, Human genetics, Genetic Loci, genetic factors, 570 Life sciences, biology, 030217 neurology & neurosurgery, Medizin, Infektionsmedicin, Genome-wide association studies, Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Pandemic, 2.1 Biological and endogenous factors, pandemi, Multidisciplinary, article, Public Health, Global Health, Social Medicine and Epidemiology, Racial Group, 10124 Institute of Molecular Life Sciences, Host-Pathogen Interaction, Multidisciplinary Sciences, Infectious Diseases, Host-Pathogen Interactions, Critical Illne, COVID-19, GWAS, genetic factors, environmental risk factors, therapy, Infectious Medicine, Coronavirus disease 2019 (COVID-19), SUSCEPTIBILITY LOCI, General Science & Technology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Computational biology, Biology, Vaccine Related, 692/699/255/2514, Environmental risk, Mendelian randomization, COVID-19 Host Genetics Initiative, QH426, 631/326/596/4130, 030304 developmental biology, Inflammation, therapy, SARS-CoV-2, Human Genome, COVID-19, Genetic architecture, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Emerging Infectious Diseases, Good Health and Well Being, Viral infection, 3111 Biomedicine
Abstract: Niemi, Mari E. K. et al. 39 páginas, figuras y tablas. Contiene material suplementario., The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Published: 2021

24. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Peter Kovacs, Alan F. Wright, Stephen Turner, Michèle M. Sale, Siim Sõber, Janoš Terzić, Elin Org, Richard S. Cooper, Alena Stančáková, Jerome I. Rotter, W. H. Linda Kao, Albert Hofman, Andrew B. Singleton, Florian Kronenberg, Jianjun Liu, Nicole L. Glazer, Christopher W. Knouff, Jennifer L. Bragg-Gresham, Juha Karjalainen, Li Ching Chang, Benjamin J. Wright, Jacqueline C.M. Witteman, Martin G. Larson, Klaus Stark, Richard J. Rodeheffer, Sharon L.R. Kardia, Douglas M. Ruderfer, Sheila Ulivi, Madhumathi Rao, Andrew A. Hicks, Eva Brand, Viviane Nicaud, Stephen G. Ball, Anna Köttgen, Germaine C. Verwoert, Anders Hamsten, Nick Shrine, Uwe Völker, Stefan Kloiber, Stephen Hancock, Emelia J. Benjamin, Bok Ghee Han, Kenneth Rice, Mark Woodward, Veronique Vitart, Karl Andersen, Nicholas J. Wareham, Robert Roberts, Maja Barbalić, David Couper, Yukinori Okada, André G. Uitterlinden, Sekar Kathiresan, Leo-Pekka Lyytikäinen, Pankaj Arora, Tatijana Zemunik, David S. Siscovick, Simonetta Guarrera, Dawn M. Waterworth, Tatjana Stojakovic, Braxton D. Mitchell, Devin Absher, Carmen A. Peralta, Mika Kivimäki, Xueling Sim, Norihiro Kato, Philippe Froguel, Keith L. Keene, Donna K. Arnett, Naoyuki Kamatani, Tazeen H. Jafar, Idris Guessous, Gunnar Jacobs, Michael M. Hoffmann, Kari Stefansson, Christian Hengstenberg, Tomonori Okamura, Inga Prokopenko, Christina Willenborg, Peter S. Braund, Rainer Rettig, Francesco U.S. Mattace-Raso, Vikal Tripathy, F. Gerald R. Fowkes, Laura R. Loehr, Harry Campbell, Margherita Cavalieri, Olle Melander, Hao Mei, I. Mateo Leach, Nicholette D. Palmer, Eva Albrecht, Naoharu Iwai, Stefan Martin Brand, Toshiko Tanaka, Jackie A. Cooper, Omri Gottesman, Manuela Uda, Angelo Scuteri, Aroon D. Hingorani, Cristiano Fava, Yusuke Nakamura, Jiang He, Min Jin Go, Serge Hercberg, Wendy L. McArdle, Philipp S. Wild, Florian Ernst, Paul Mitchell, Wolfgang Koenig, Caroline S. Fox, S. J.Cathy Fann, Janine F. Felix, Anna F. Dominiczak, Mike A. Nalls, Erik Ingelsson, Mario A. Morken, Susana Eyheramendy, Christopher Newton-Cheh, Igor Rudan, D. G. Vinay, Christopher P. Nelson, Ervin R. Fox, Xiuqing Guo, Jing Hua Zhao, Rick Twee-Hee Ong, Margaret M. Redfield, Oscar H. Franco, Yongmei Liu, Fulvio Ricceri, Mark A. Hlatky, Bernhard Paulweber, Mingyao Li, Themistocles L. Assimes, Karl Winkler, Inês Barroso, Sylvia E. Rosas, M Walker, Richard W Morris, Bo Hedblad, Hakon Hakonarson, Sonny Dandona, Peter H. Whincup, Martin Adam, Vilmundur Gudnason, Daniel Ackermann, Qiong Yang, Cuno S. P. M. Uiterwaal, Paul M. Ridker, George Davey Smith, Li Chen, C. Sinning, Terri L. Young, Jer-Yuarn Wu, Walter Palmas, Will Longstreth, Joe Devaney, Pavel Hamet, Xiaofeng Zhu, Fredrik Nyberg, Wilfried Renner, Anuj Goel, L. Adrienne Cupples, Nish Chaturvedi, Iftikhar J. Kullo, Nicholas D. Hastie, Aude Saint-Pierre, Panos Deloukas, Smita R. Kulkarni, Eric Boerwinkle, Wolfram Goessling, Gian Andri Thun, Eric J.G. Sijbrands, Shih-Jen Hwang, Carole Proust, Hirotsugu Ueshima, Kristian Hveem, Pierre Meneton, Joshua C. Denny, Olivier Devuyst, Kerri L. Wiggins, Ming-Huei Chen, Robert W. Lawrence, Robert L. Wilensky, Andre Franke, Nicole Soranzo, Simon Heath, Margot Haun, Karlhans Endlich, David Altshuler, Harald Grallert, Laurence Tiret, Luigi Ferrucci, Caroline Hayward, Sudha Seshadri, Bénédicte Stengel, Lynne E. Wagenknecht, John Attia, Andreas Ziegler, Renate B. Schnabel, Stefan Schreiber, Santosh Dahgam, Kurt Lohman, Christian M. Shaffer, Barbara Ludwig, Katalin Susztak, Chien-Hsiun Chen, Michele K. Evans, Paolo Vineis, Guo Li, Thomas J. Wang, Meena Kumari, Heather M. Stringham, Bruce M. Psaty, Norman Klopp, Halit Ongen, Ben A. Oostra, Stefan Coassin, Petra Bruse, Wei-Min Chen, Unnur Thorsteinsdottir, Charles N. Rotimi, Robert J. Carroll, Muredach P. Reilly, Niek Verweij, Dena G. Hernandez, Amy J. Swift, Barbara Kollerits, Hyung Lae Kim, Cristian Pattaro, Ivana Kolcic, Ronit Katz, John M. C. Connell, Dan E. Arking, Albert W. Dreisbach, Peter Vollenweider, C. S. Janipalli, Jian'an Luan, Erkki Vartiainen, James T. Willerson, John R. Thompson, Daniela Toniolo, Lyle J. Palmer, Alexander Teumer, Serkalem Demissie-Banjaw, Stella Trompet, James E. Hixson, Sue Shaw-Hawkins, Rossella Sorice, Bernhard R. Winkelmann, John Danesh, Anthony J. Balmforth, Toshio Ogihara, Jyotika K. Fernandes, Ulf Gyllensten, Ville Aalto, Åsa Johansson, Andres Metspalu, John F. Peden, Diana Kuh, Medea Imboden, Antonio Lupo, Su Chi Lim, Young-Jin Kim, Giovanni Malerba, Yurii S. Aulchenko, Satoshi Umemura, Ioanna Tzoulaki, Alan B. Weder, Helena Schmidt, Gerjan Navis, Susan R. Heckbert, Hans J. Rupprecht, Edward G. Lakatta, Christian Gieger, Najaf Amin, Paul Muntner, Lenore J. Launer, Ivana Persico, Hugh Watkins, Ian Ford, K. Radha Mani, Sylvia Stracke, Johanna Kuusisto, John Chalmers, Muhammad Islam, Lars Lind, Stefan R. Bornstein, Marjo-Riitta Järvelin, J. H. Young, Reiner Biffar, Santhi K. 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O'Reilly, David Hadley, Hermann Brenner, Paolo Gasparini, Nanette R. Lee, Bamidele O. Tayo, Robert Clarke, Henri Wallaschofski, Marketa Sjögren, Abbas Dehghan, Melanie Waldenberger, Neil Risch, Vasyl Pihur, Jessica D. Faul, François Cambien, Christian Fuchsberger, Nicholas G. Martin, John C. Chambers, Zouhair Aherrahrou, Karl J. Lackner, Leif Groop, Matthias Olden, Wiek H. van Gilst, Mathias Gorski, Yvonne T. van der Schouw, Patrick Diemert, Christoph Bickel, Yik Ying Teo, Giorgio Pistis, Ruth J. F. Loos, Gudrun Veldre, Thorsten Reffelmann, Lude Franke, Karen L. Mohlke, Stefan Blankenberg, Massimo Mangino, Ian N. M. Day, Atsushi Takahashi, Alan B. Zonderman, Hua Tang, Reijo Laaksonen, Holly Kramer, Gary C. Curhan, Adrienne Tin, Talin Haritunians, Loic Yengo, Philip Howard, Arnika Kathleen Wagner, Anna Maria Corsi, Yen Pei C. Chang, Karin Halina Greiser, Jeanette Erdmann, Solveig Gretarsdottir, Sanjay Kinra, Alex Parker, Belen Ponte, Marina Ciullo, Michael Preuss, Tin Aung, Nicholas L. Smith, Michiaki Kubo, Richard N. Bergman, Alan S. Go, Patricia P. Chang, Gudmundur Thorgeirsson, Christa Meisinger, Gonçalo R. Abecasis, Maria Blettner, Jaana Laitinen, Daniel Taliun, Carlos Iribarren, Paavo Zitting, Thomas Lumley, Andreas Meinitzer, Wayne D. Rosamond, Daehee Kang, Johanne Tremblay, Stephan B. Felix, Colin A. McKenzie, Yuan-Tsong Chen, Lyudmyla Kedenko, Mladen Boban, Fadi J. Charchar, Adebowale Adeyemo, Brendan M. Buckley, Jennifer A. Smith, Reinhold Schmidt, Jaspal S. Kooner, Gavin Lucas, Paul Elliott, Dorairajan Prabhakaran, Tune H. Pers, Tunde Salako, Terrence Forrester, Paul Burton, Jeffrey R. Gulcher, Kelly A. Volcik, Richard M. Myers, Andreas Tomaschitz, H.-Erich Wichmann, Jie Yao, Giuseppe Matullo, Carsten A. Böger, Henry Völzke, Daniela Ruggiero, Federico Murgia, Yoshikuni Kita, Augustine Kong, Giovanni Gambaro, Cinzia Sala, Peter P. Pramstaller, James Scott, Maris Laan, Laura J. Scott, Alistair S. Hall, Sanaz Sedaghat, James F. Wilson, Joanne M. Murabito, Yi-An Ko, Honghuang Lin, Mark Seielstad, Leena Peltonen, Sven Bergmann, Thomas Meitinger, Matthias Nauck, María Soler Artigas, Thomas Illig, Nanette I. Steinle, Samer S. Najjar, Christina Loley, Debbie A Lawlor, Steven C. Hunt, Yali Li, Weihua Zhang, Jie Jin Wang, Daniele Cusi, Marco Orrù, Stephen P. Fortmann, Melissa Garcia, Barry I. Freedman, Joseph M. Lindsay, Juan P. Casas, Tomohiro Katsuya, Grant W. Montgomery, Hubert Scharnagl, Khanh-Dung H. Nguyen, Steven M. Schwartz, Afshin Parsa, Elizabeth G. Holliday, Murielle Bochud, Kiran Musunuru, Bruno H. Stricker, Lori L. Bonnycastle, Ilja M. Nolte, Timothy M. Frayling, Stefan Enroth, Michiel L. Bots, Mark J. Caulfield, Laura Portas, Vincent Chouraki, Carl D. Langefeld, Eran Halperin, Shufeng Chen, Philippa J. Talmud, Terho Lehtimäki, Steve E. Humphries, Gudmar Thorleifsson, Anika Grosshennig, Norbert Watzinger, Fumihiko Takeuchi, Pim van der Harst, Takayoshi Ohkubo, Nabila Bouatia-Naji, Erwin P. 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Tobin, Joban Sehmi, Janja Nahrstedt, E. Shyong Tai, Thor Aspelund, Jürgen Grässler, Hilma Holm, Matthew Denniff, Joshua W. Knowles, Tien Yin Wong, Erika Salvi, James F. Meschia, Dongfeng Gu, Ron Waksman, Stacey Gabriel, Judith A. Hoffman Bolton, Michael Boehnke, Johannes Haerting, Darina Czamara, Heribert Schunkert, Thomas Quertermous, Peter M. Nilsson, Jong-Young Lee, Yasuharu Tabara, Chittaranjan S. Yajnik, Daniel Levy, John Beilby, Fernando Rivadeneira, Claire Perret, Gudny Eiriksdottir, Jingzhong Ding, George A. Wells, Harold Snieder, Ayo P. Doumatey, Dag S. Thelle, Anja Medack, N. Charlotte Onland-Moret, Michael Stumvoll, David Ellinghaus, Ingrid B. Borecki, Tatsuhiko Tsunoda, Ian H. de Boer, M. Arfan Ikram, Andrew M. Taylor, Johannes H. Smit, Gary F. Mitchell, Anna-Liisa Hartikainen, Markku Laakso, Mark McEvoy, Andrew S. Plump, Toby Johnson, Cornelia M. van Duijn, Ozren Polasek, Wilmar Igl, Vincent Mooser, Rodney J. 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Jafar, TH., Janipalli, CS., Johnson, T., Kathiresan, S., Khaw, KT., Kim, HL., Kinra, S., Kita, Y., Kivimaki, M., Kooner, JS., Kumar, MJ., Kuh, D., Kulkarni, SR., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, EG., Langefeld, CD., Larson, MG., Lathrop, M., Lawlor, DA., Lawrence, RW., Lee, JY., Lee, NR., Levy, D., Li, Y., Longstreth, WT., Luan£££Jian'an£££ J., Lucas, G., Ludwig, B., Mangino, M., Mani, KR., Marmot, MG., Mattace-Raso, FU., Matullo, G., McArdle, WL., McKenzie, CA., Meitinger, T., Melander, O., Meneton, P., Meschia, JF., Miki, T., Milaneschi, Y., Mohlke, KL., Mooser, V., Morken, MA., Morris, RW., Mosley, TH., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, KD., Nilsson, P., Nyberg, F., O'Donnell, CJ., Ogihara, T., Ohkubo, T., Okamura, T., Ong, RT., Ongen, H., Onland-Moret, NC., O'Reilly, PF., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, LJ., Palmer, ND., Parker, AN., Peden, JF., Peltonen, L., Perola, M., Pihur, V., Platou, CG., Plump, A., Prabhakaran, D., Psaty, BM., Raffel, LJ., Rao, DC., Rasheed, A., Ricceri, F., Rice, KM., Rosengren, A., Rotter, JI., Rudock, ME., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, NJ., Schwartz, SM., Schwarz, PE., Scott, LJ., Scott, J., Scuteri, A., Sehmi, JS., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, NR., Sijbrands, EJ., Sim, X., Singleton, A., Sjögren, M., Smith, NL., Soler Artigas, M., Spector, TD., Staessen, JA., Stancakova, A., Steinle, NI., Strachan, DP., Stringham, HM., Sun, YV., Swift, AJ., Tabara, Y., Tai, ES., Talmud, PJ., Taylor, A., Terzic, J., Thelle, DS., Tobin, MD., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, CS., Umemura, S., van der Harst, P., van der Schouw YT., van Gilst WH., Vartiainen, E., Vasan, RS., Veldre, G., Verwoert, GC., Viigimaa, M., Vinay, DG., Vineis, P., Voight, BF., Vollenweider, P., Wagenknecht, LE., Wain, LV., Wang, X., Wang, TJ., Wareham, NJ., 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Subjects: 0301 basic medicine, Nephrology, Genetics and Molecular Biology (all), estimated glomerular filtration rate, estimated glomerular filtration rate, chronic kidney disease, genetic determinants, General Physics and Astronomy, Kidney development, Genome-wide association study, Biochemistry, Settore MED/14 - NEFROLOGIA, Renal Insufficiency, Chronic, Genetics, AGEN Consortium, ddc:616, education.field_of_study, Kidney, Stage renal-disease, Multidisciplinary, Genome-wide association, CHARGe-Heart Failure Group, Gene Expression Regulation, Genome-Wide Association Study, Genotype, Humans, Renal Insufficiency, Chronic, Genetic Predisposition to Disease, Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Physics and Astronomy (all), Metaanalysis, Renal Insufficiency, Chronic/genetics, Biological sciences, Serum creatinine, medicine.anatomical_structure, Efficient, Ronyons -- Fisiologia, Hypertension, ICBP Consortium, Transmembrane transporter activity, genetic association, loci, kidney function, CARDIOGRAM, Human, medicine.medical_specialty, Science, Population, Renal function, ECHOGen Consortium, Replication, Biology, Environment, Research Support, General Biochemistry, Genetics and Molecular Biology, N.I.H, genetic determinants, 03 medical and health sciences, GENOME-WIDE ASSOCIATION, FALSE DISCOVERY RATES, STAGE RENAL-DISEASE, SERUM CREATININE, METAANALYSIS, VARIANTS, INDIVIDUALS, POPULATION, RISK, HYPERTENSION, Kidney function, Research Support, N.I.H., Extramural, Internal medicine, MD Multidisciplinary, medicine, Journal Article, eGFRcrea, eGFRcys, ddc:610, Genetik, Mortality, education, ddc:613, urogenital system, Individuals, Extramural, General Chemistry, ta3121, medicine.disease, R1, 030104 developmental biology, 570 Life sciences, biology, Genètica, chronic kidney disease, Kidney disease, Meta-Analysis
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. J.T. and P.H. are consultants for Servier. J.C. received research grants and honoraria from Servier. K.S. obtained research support from Boehringer Ingelheim. The remaining authors declared no competing financial interests.
Published: 2016

25. Genome-wide association study identifies two loci strongly affecting transferrin glycosylation

Author: Peter Vollenweider, Sven Bergmann, Zoltán Kutalik, Vincent Mooser, Nicholas G. Martin, Pedro Marques-Vidal, Beben Benyamin, Grant W. Montgomery, Jacques S. Beckmann, Gérard Waeber, Pamela A. F. Madden, John Whitfield, Andrew C. Heath, Kutalik, Zoltán, Benyamin, Beben, Bergmann, Sven, Mooser, Vincent, Waeber, Gérard, Montgomery, Grant W, Martin, Nicholas G, Madden, Pamela AF, Heath, Andrew C, Beckmann, Jacques S, Vollenweider, Peter, Marques-Vidal, Pedro, and Whitfield, John B
Subjects: Adult, Male, Glycosylation, Alcohol Drinking, glycosylation, Population, Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, White People, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, PGM1, Genetics, Humans, SNP, transferrin, Allele, education, Molecular Biology, Genetics (clinical), Aged, 030304 developmental biology, Aged, 80 and over, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, education.field_of_study, genome-wide association study, Association Studies Articles, Transferrin, General Medicine, Middle Aged, Molecular biology, 3. Good health, chemistry, Chromosome 3, Female, Switzerland, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Polysaccharide sidechains attached to proteins play important roles in cell-cell and receptor-ligand interactions. Variation in the carbohydrate component has been extensively studied for the iron transport protein transferrin, because serum levels of the transferrin isoforms asialotransferrin 1 disialotransferrin (carbohydrate-deficient transferrin, CDT) are used as biomarkers of excessive alcohol intake. We conducted a genome-wide association study to assess whether genetic factors affect CDT concentration in serum. CDT was measured in three population-based studies: one in Switzerland (CoLaus study, n = 5181) and two in Australia (n = 1509, n = 775). The first cohort was used as the discovery panel and the latter ones served as replication. Genome-wide single-nucleotide polymorphism (SNP) typing data were used to identify loci with significant associations with CDT as a percentage of total transferrin (CDT%). The top three SNPs in the discovery panel (rs2749097 near PGM1 on chromosome 1, and missense polymorphisms rs1049296, rs1799899 in TF on chromosome 3) were successfully replicated, yielding genome-wide significant combined association with CDT% (P = 1.9 × 10 -9 , 4 × 10 -39 , 5.5 × 10 -43 , respectively) and explain 5.8% of the variation in CDT%. These allelic effects are postulated to be caused by variation in availability of glucose-1-phosphate as a precursor of the glycan (PGM1), and variation in transferrin (TF) structure. Refereed/Peer-reviewed
Published: 2011
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25 results on '"Mooser,Vincent"'

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23. Mapping the human genetic architecture of COVID-19

24. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

25. Genome-wide association study identifies two loci strongly affecting transferrin glycosylation

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