Author: "Lyytikäinen, Leo-Pekka" / Publisher: springer nature - Searchworks@Jio Institute Digital Library Search Results

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1. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Author: Winkler, Thomas W., Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X., Stanzick, Kira J., Thomas, Laurent F., Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y., Tayo, Bamidele, Thio, Chris H. L., Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B., Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J., Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P. J., Zonderman, Alan B., Smith, Albert V., Oldehinkel, Albertine J., De Grandi, Alessandro, Rosenkranz, Alexander R., Franke, Andre, Teren, Andrej, Metspalu, Andres, Hicks, Andrew A., Morris, Andrew P., Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I., Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I., Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K., Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H., Ning, Boting, Penninx, Brenda W. J. H., Vanderwerff, Brett R., Psaty, Bruce M., Kammerer, Candace M., Langefeld, Carl D., Hayward, Caroline, Spracklen, Cassandra N., Robinson-Cohen, Cassianne, Hartman, Catharina A., Lindgren, Cecilia M., Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M., Schulz, Christina-Alexandra, Willer, Cristen J., Chasman, Daniel I., Gudbjartsson, Daniel F., Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J., Waterworth, Dawn M., Mascalzoni, Deborah, Mook-Kanamori, Dennis O., Reilly, Dermot F., Daw, E. Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N., Delgado, Graciela E., Montgomery, Grant W., Snieder, Harold, Campbell, Harry, White, Harvey D., Gao, He, Stringham, Heather M., Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holger, Kramer, Holly, Rudan, Igor, Nolte, Ilja M., Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P., Wilson, James F., Halbritter, Jan, Felix, Janine F., Divers, Jasmin, Kooner, Jaspal S., Lee, Jeannette Jen-Mai, O’Connell, Jeffrey, Rotter, Jerome I., Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C., Whitfield, John B., Gaziano, John M., Marten, Jonathan, Coresh, Josef, Jonas, Jost B., Mychaleckyj, Josyf C., Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L., Endlich, Karlhans, Dittrich, Katalin, Ryan, Kathleen A., Rice, Kenneth M., Taylor, Kent D., Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lars, Wallentin, Lars, Yerges-Armstrong, Laura M., Raffield, Laura M., Phillips, Lawrence S., Launer, Lenore J., Lyytikäinen, Leo-Pekka, Lange, Leslie A., Citterio, Lorena, Klaric, Lucija, Ikram, M. Arfan, Ising, Marcus, Kleber, Marcus E., Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Markus, Perola, Markus, de Borst, Martin H., Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F., Biggs, Mary L., Wojczynski, Mary K., Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthias, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H., Stumvoll, Michael, Province, Michael A., Evans, Michele K., O’Donoghue, Michelle L., Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A., Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G., Tan, Nicholas Y. Q., Palmer, Nicholette D., Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T., Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P., Sulem, Patrick, Magnusson, Patrik K. E., Elliott, Paul, Ridker, Paul M., Hamet, Pavel, Svensson, Per O., Joshi, Peter K., Kovacs, Peter, Pramstaller, Peter P., Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z. H., Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M., Carroll, Robert J., Gansevoort, Ron T., Loos, Ruth J. F., Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A., Graham, Sarah E., Gordon, Scott D., Hwang, Shih-Jen, Kerr, Shona M., Vaccargiu, Simona, Patil, Snehal B., Hallan, Stein, Bakker, Stephan J. L., Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S., Lehtimäki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tõnu, Haller, Toomas, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmantas, Gudnason, Vilmundur, Jaddoe, Vincent W. V., Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Hung, Adriana M., Stark, Klaus J., Stefansson, Kari, Böger, Carsten A., Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, Heid, Iris M., Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, University of Helsinki, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, Research Programs Unit, Tampere University, Clinical Medicine, TAYS Heart Centre, Department of Clinical Chemistry, Department of Clinical Physiology and Nuclear Medicine, Internal Medicine, Pediatrics, Epidemiology, Radiology & Nuclear Medicine, Erasmus MC other, Home Office, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), UK DRI Ltd, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Winkler, Thomas W, Rasheed, Humaira, Teumer, Alexander, Gorski, Mathia, Rowan, Bryce X, Stanzick, Kira J, Thomas, Laurent F, Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y, Tayo, Bamidele, Thio, Chris H L, Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B, Horn, Katrin, Li, Man, Scholz, Marku, Cocca, Massimiliano, Wuttke, Matthia, van der Most, Peter J, Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abba, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P J, Zonderman, Alan B, Smith, Albert V, Oldehinkel, Albertine J, De Grandi, Alessandro, Rosenkranz, Alexander R, Franke, Andre, Teren, Andrej, Metspalu, Andre, Hicks, Andrew A, Morris, Andrew P, Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I, Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I, Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K, Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H, Ning, Boting, Penninx, Brenda W J H, Vanderwerff, Brett R, Psaty, Bruce M, Kammerer, Candace M, Langefeld, Carl D, Hayward, Caroline, Spracklen, Cassandra N, Robinson-Cohen, Cassianne, Hartman, Catharina A, Lindgren, Cecilia M, Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M, Schulz, Christina-Alexandra, Willer, Cristen J, Chasman, Daniel I, Gudbjartsson, Daniel F, Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J, Waterworth, Dawn M, Mascalzoni, Deborah, Mook-Kanamori, Dennis O, Reilly, Dermot F, Daw, E Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P, Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N, Delgado, Graciela E, Montgomery, Grant W, Snieder, Harold, Campbell, Harry, White, Harvey D, Gao, He, Stringham, Heather M, Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holgen, Kramer, Holly, Rudan, Igor, Nolte, Ilja M, Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P, Wilson, James F, Halbritter, Jan, Felix, Janine F, Divers, Jasmin, Kooner, Jaspal S, Lee, Jeannette Jen-Mai, O'Connell, Jeffrey, Rotter, Jerome I, Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C, Whitfield, John B, Gaziano, John M, Marten, Jonathan, Coresh, Josef, Jonas, Jost B, Mychaleckyj, Josyf C, Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L, Endlich, Karlhan, Dittrich, Katalin, Ryan, Kathleen A, Rice, Kenneth M, Taylor, Kent D, Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lar, Wallentin, Lar, Yerges-Armstrong, Laura M, Raffield, Laura M, Phillips, Lawrence S, Launer, Lenore J, Lyytikäinen, Leo-Pekka, Lange, Leslie A, Citterio, Lorena, Klaric, Lucija, Ikram, M Arfan, Ising, Marcu, Kleber, Marcus E, Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Marku, Perola, Marku, de Borst, Martin H, Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F, Biggs, Mary L, Wojczynski, Mary K, Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthia, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H, Stumvoll, Michael, Province, Michael A, Evans, Michele K, O'Donoghue, Michelle L, Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A, Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G, Tan, Nicholas Y Q, Palmer, Nicholette D, Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T, Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P, Sulem, Patrick, Magnusson, Patrik K E, Elliott, Paul, Ridker, Paul M, Hamet, Pavel, Svensson, Per O, Joshi, Peter K, Kovacs, Peter, Pramstaller, Peter P, Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z H, Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M, Carroll, Robert J, Gansevoort, Ron T, Loos, Ruth J F, Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A, Graham, Sarah E, Gordon, Scott D, Hwang, Shih-Jen, Kerr, Shona M, Vaccargiu, Simona, Patil, Snehal B, Hallan, Stein, Bakker, Stephan J L, Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S, Lehtimäki, Terho, Boutin, Thibaud S, Meitinger, Thoma, Wong, Tien-Yin, Bergler, Tobia, Rabelink, Ton J, Esko, Tõnu, Haller, Tooma, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmanta, Gudnason, Vilmundur, Jaddoe, Vincent W V, Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Stark, Klaus J, Stefansson, Kari, Böger, Carsten A, Hung, Adriana M, Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, Heid, Iris M, and Lee Kong Chian School of Medicine (LKCMedicine)
Subjects: Life Sciences & Biomedicine - Other Topics, EXPRESSION, Diabetic Nephropathies/genetics, 610 Medizin, LOCI, Medicine (miscellaneous), EFFICIENT, Lifelines cohort study, Kidney, General Biochemistry, Genetics and Molecular Biology, DISEASE, QUALITY-CONTROL, SDG 3 - Good Health and Well-being, Diabetic Nephropathy, Diabetes Mellitus, Humans, Medicine [Science], Diabetic Nephropathies, GENOME-WIDE ASSOCIATION, Biology, DiscovEHR/MyCode study, METAANALYSIS, Glomerular Filtration Rate/genetics, Medicinsk genetik, ddc:610, Science & Technology, genetic, effects, kidney, diabetic, JOINT, Klinisk medicin, Diabetes Mellitu, 3126 Surgery, anesthesiology, intensive care, radiology, Multidisciplinary Sciences, ENVIRONMENT INTERACTION, Creatinine, VA Million Veteran Program, Science & Technology - Other Topics, 3111 Biomedicine, Clinical Medicine, SMOKING, General Agricultural and Biological Sciences, Life Sciences & Biomedicine, Medical Genetics, Human, Genome-Wide Association Study, Glomerular Filtration Rate
Abstract: Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM. Published version The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) supported the meta-analysis—Project-ID 387509280—SFB1350 (Subproject C6 to I.M.H.). A.M.H., B.R., and R.T. were supported by VACSR&D MVP grant CX001897. This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by VACSR&D MVP grant CX001897 (A.M.H.). This publication does not represent the views of the Department of Veteran Affairs or the United States Government. We conducted this research using the UK Biobank resource under the application number 20272.
Published: 2022

2. Uncovering the complex genetic architecture of human plasma lipidome using machine learning methods.

Author: Lehtimäki, Miikael, H. Mishra, Binisha, Del-Val, Coral, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Cloninger, C. Robert, Raitakari, Olli T., Laaksonen, Reijo, Zwir, Igor, Lehtimäki, Terho, and Mishra, Pashupati P.
Subjects: MACHINE learning, GENETIC variation, METABOLIC regulation, BLOOD lipids, LIPID metabolism
Abstract: Genetic architecture of plasma lipidome provides insights into regulation of lipid metabolism and related diseases. We applied an unsupervised machine learning method, PGMRA, to discover phenotype-genotype many-to-many relations between genotype and plasma lipidome (phenotype) in order to identify the genetic architecture of plasma lipidome profiled from 1,426 Finnish individuals aged 30–45 years. PGMRA involves biclustering genotype and lipidome data independently followed by their inter-domain integration based on hypergeometric tests of the number of shared individuals. Pathway enrichment analysis was performed on the SNP sets to identify their associated biological processes. We identified 93 statistically significant (hypergeometric p-value < 0.01) lipidome-genotype relations. Genotype biclusters in these 93 relations contained 5977 SNPs across 3164 genes. Twenty nine of the 93 relations contained genotype biclusters with more than 50% unique SNPs and participants, thus representing most distinct subgroups. We identified 30 significantly enriched biological processes among the SNPs involved in 21 of these 29 most distinct genotype-lipidome subgroups through which the identified genetic variants can influence and regulate plasma lipid related metabolism and profiles. This study identified 29 distinct genotype-lipidome subgroups in the studied Finnish population that may have distinct disease trajectories and therefore could be useful in precision medicine research. [ABSTRACT FROM AUTHOR]
Published: 2023
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3. C-type lectin receptor CLEC4A2 promotes tissue adaptation of macrophages and protects against atherosclerosis.

Author: Park, Inhye, Goddard, Michael E., Cole, Jennifer E., Zanin, Natacha, Lyytikäinen, Leo-Pekka, Lehtimäki, Terho, Andreakos, Evangelos, Feldmann, Marc, Udalova, Irina, Drozdov, Ignat, and Monaco, Claudia
Subjects: MACROPHAGE colony-stimulating factor, TOLL-like receptors, MACROPHAGES, CHOLESTEROL metabolism, BONE marrow, ATHEROSCLEROSIS
Abstract: Macrophages are integral to the pathogenesis of atherosclerosis, but the contribution of distinct macrophage subsets to disease remains poorly defined. Using single cell technologies and conditional ablation via a LysMCre+Clec4a2flox/DTR mouse strain, we demonstrate that the expression of the C-type lectin receptor CLEC4A2 is a distinguishing feature of vascular resident macrophages endowed with athero-protective properties. Through genetic deletion and competitive bone marrow chimera experiments, we identify CLEC4A2 as an intrinsic regulator of macrophage tissue adaptation by promoting a bias in monocyte-to-macrophage in situ differentiation towards colony stimulating factor 1 (CSF1) in vascular health and disease. During atherogenesis, CLEC4A2 deficiency results in loss of resident vascular macrophages and their homeostatic properties causing dysfunctional cholesterol metabolism and enhanced toll-like receptor triggering, exacerbating disease. Our study demonstrates that CLEC4A2 licenses monocytes to join the vascular resident macrophage pool, and that CLEC4A2-mediated macrophage homeostasis is critical to combat cardiovascular disease. The contribution of distinct subsets of macrophages to atherosclerosis is poorly understood. Here the authors describe a protective subset of vascular macrophages expressing the C-type lectin receptor CLEC4A2, which licenses monocytes to join the resident vascular macrophage pool and ensures vascular homeostasis. [ABSTRACT FROM AUTHOR]
Published: 2022
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4. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways.

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., and Evans, Daniel S.
Subjects: BRUGADA syndrome, ARRHYTHMIA, LOCUS (Genetics), VENTRICULAR arrhythmia, DISEASE risk factors, CARDIAC arrest, SUDDEN death, CELL anatomy
Abstract: The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization. The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. [ABSTRACT FROM AUTHOR]
Published: 2022
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5. Prehospital Adenosine Diphosphate Receptor Blocker Use, Culprit Artery Flow, and Mortality in STEMI: The MADDEC Study.

Author: Hautamäki, Markus, Lyytikäinen, Leo-Pekka, Eskola, Markku, Lehtimäki, Terho, Nikus, Kjell, Oksala, Niku, Tynkkynen, Juho, and Hernesniemi, Jussi
Subjects: *ADENOSINE diphosphate, *ACUTE coronary syndrome, *PERCUTANEOUS coronary intervention, *PRASUGREL, *ARTERIES
Abstract: Background and Objective: The newer adenosine diphosphate (ADP) receptor blockers ticagrelor and prasugrel are superior to clopidogrel in the long-term management of acute coronary syndrome (ACS). We evaluated the acute performance (prehospital loading) of these ADP receptor blockers in a primary percutaneous coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI). Methods: In a retrospective, single-center registry study, data on all STEMI patients admitted for their first primary PCI between January 2007 and April 2020 were analyzed (n = 3218). The three ADP receptor blockers were mainly used during consecutive periods (clopidogrel 2007–2010, prasugrel 2011–2014, and ticagrelor 2014–2020), and were compared with risk factor-adjusted multivariate logistic regression for acute 3- and 7-day mortality and culprit artery flow before and after PCI. Results: Of the 3218 total patients, 47.6% (n = 1532) were treated with ticagrelor, 22.1% (n = 711) were treated with prasugrel, and 30.3% (n = 975) were treated with clopidogrel. The use of ticagrelor or prasugrel as opposed to clopidogrel was associated with better culprit artery flow before PCI (odds ratio [OR] 1.21 for moderate or good flow, 95% confidence interval [CI] 1.03–1.42, p = 0.022), as well as lower acute mortality (OR 0.66 for 3-day mortality, 95% CI 0.46–0.95, p = 0.025; and OR 0.71 for 7-day mortality, 95% CI 0.52–0.98, p = 0.039). The results in regard to acute mortality were highlighted among patients with short treatment delays (disappearing with longer treatment delays; p < 0.05 for interaction). Conclusions: The newer ADP receptor blockers are associated with lower mortality and better culprit artery flow at presentation when compared with clopidogrel. There are no significant differences between the two newer drugs. As the drugs were mainly used during three consecutive periods, unmeasured confounding related to the development of cardiac care and changes in the population may contribute to the results. [ABSTRACT FROM AUTHOR]
Published: 2021
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6. Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health.

Author: Marttila, Saara, Rovio, Suvi, Mishra, Pashupati P., Seppälä, Ilkka, Lyytikäinen, Leo-Pekka, Juonala, Markus, Waldenberger, Melanie, Oksala, Niku, Ala-Korpela, Mika, Harville, Emily, Hutri-Kähönen, Nina, Kähönen, Mika, Raitakari, Olli, Lehtimäki, Terho, and Raitoharju, Emma
Subjects: PREMATURE labor, TYPE 2 diabetes, MICRORNA, PHENOTYPES, GENE expression
Abstract: Preterm birth (PTB) is associated with increased risk of type 2 diabetes and neurocognitive impairment later in life. We analyzed for the first time the associations of PTB with blood miRNA levels in adulthood. We also investigated the relationship of PTB associated miRNAs and adulthood phenotypes previously linked with premature birth. Blood MicroRNA profiling, genome-wide gene expression analysis, computer-based cognitive testing battery (CANTAB) and serum NMR metabolomics were performed for Young Finns Study subjects (aged 34–49 years, full-term n = 682, preterm n = 84). Preterm birth (vs. full-term) was associated with adulthood levels of hsa-miR-29b-3p in a fully adjusted regression model (p = 1.90 × 10–4, FDR = 0.046). The levels of hsa-miR-29b-3p were down-regulated in subjects with PTB with appropriate birthweight for gestational age (p = 0.002, fold change [FC] = − 1.20) and specifically in PTB subjects with small birthweight for gestational age (p = 0.095, FC = − 1.39) in comparison to individuals born full term. Hsa-miR-29b-3p levels correlated with the expressions of its target-mRNAs BCL11A and CS and the gene set analysis results indicated a target-mRNA driven association between hsa-miR-29b-3p levels and Alzheimer's disease, Parkinson's disease, Insulin signaling and Regulation of Actin Cytoskeleton pathway expression. The level of hsa-miR-29b-3p was directly associated with visual processing and sustained attention in CANTAB test and inversely associated with serum levels of VLDL subclass component and triglyceride levels. In conlcusion, adult blood levels of hsa-miR-29b-3p were lower in subjects born preterm. Hsa-miR-29b-3p associated with cognitive function and may be linked with adulthood morbidities in subjects born preterm, possibly through regulation of gene sets related to neurodegenerative diseases and insulin signaling as well as VLDL and triglyceride metabolism. [ABSTRACT FROM AUTHOR]
Published: 2021
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7. Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts.

Author: Laaksonen, Jaakko, Mishra, Pashupati P., Seppälä, Ilkka, Lyytikäinen, Leo-Pekka, Raitoharju, Emma, Mononen, Nina, Lepistö, Maija, Almusa, Henrikki, Ellonen, Pekka, Hutri-Kähönen, Nina, Juonala, Markus, Raitakari, Olli, Kähönen, Mika, Salonen, Jukka T., and Lehtimäki, Terho
Subjects: HYPERTENSION, NON-communicable diseases, DISEASE risk factors, MITOCHONDRIAL DNA, SINGLE nucleotide polymorphisms
Abstract: High blood pressure (BP) is a major risk factor for many noncommunicable diseases. The effect of mitochondrial DNA single-nucleotide polymorphisms (mtSNPs) on BP is less known than that of nuclear SNPs. We investigated the mitochondrial genetic determinants of systolic, diastolic, and mean arterial BP. MtSNPs were determined from peripheral blood by sequencing or with genome-wide association study SNP arrays in two independent Finnish cohorts, the Young Finns Study and the Finnish Cardiovascular Study, respectively. In total, over 4200 individuals were included. The effects of individual common mtSNPs, with an additional focus on sex-specificity, and aggregates of rare mtSNPs grouped by mitochondrial genes were evaluated by meta-analysis of linear regression and a sequence kernel association test, respectively. We accounted for the predicted pathogenicity of the rare variants within protein-encoding and the tRNA regions. In the meta-analysis of 87 common mtSNPs, we did not observe significant associations with any of the BP traits. Sex-specific and rare-variant analyses did not pinpoint any significant associations either. Our results are in agreement with several previous studies suggesting that mtDNA variation does not have a significant role in the regulation of BP. Future studies might need to reconsider the mechanisms thought to link mtDNA with hypertension. [ABSTRACT FROM AUTHOR]
Published: 2021
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8. Fine mapping the CETP region reveals a common intronic insertion associated to HDL-C

Author: Experimentele Afd. Cardiologie 1, UMC Utrecht, Circulatory Health, Onderzoek Vrouw Hart & Vaatziekten, van Leeuwen, Elisabeth M., Huffman, Jennifer E., Bis, Joshua C., Isaacs, Aaron, Mulder, Monique, Sabo, Aniko, Smith, Albert V., Demissie, Serkalem, Manichaikul, Ani, Brody, Jennifer A., Feitosa, Mary F., Duan, Qing, Schraut, Katharina E., Navarro, Pau, van Vliet-Ostaptchouk, Jana V., Zhu, Gu, Mbarek, Hamdi, Trompet, Stella, Verweij, Niek, Lyytikäinen, Leo Pekka, Deelen, Joris, Nolte, Ilja M., van der Laan, Sander W., Davies, Gail, Vermeij-Verdoold, Andrea J.M., van Oosterhout, Andy A.L.J., Vergeer-Drop, Jeannette M., Arking, Dan E., Trochet, Holly, Medina-Gomez, Carolina, Rivadeneira, Fernando, Uitterlinden, Andre G., Dehghan, Abbas, Franco, Oscar H., Sijbrands, Eric J., Hofman, Albert, White, Charles C., Mychaleckyj, Josyf C., Peloso, Gina M., Swertz, Morris A., Willemsen, Gonneke, de Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W.J.H., Ford, Ian, Buckley, Brendan M., de Craen, Anton J.M., Starr, John M., Deary, Ian J., Pasterkamp, Gerard, Generation Scotland, LifeLines Cohort Study, CHARGE Lipids Working Group, Experimentele Afd. Cardiologie 1, UMC Utrecht, Circulatory Health, Onderzoek Vrouw Hart & Vaatziekten, van Leeuwen, Elisabeth M., Huffman, Jennifer E., Bis, Joshua C., Isaacs, Aaron, Mulder, Monique, Sabo, Aniko, Smith, Albert V., Demissie, Serkalem, Manichaikul, Ani, Brody, Jennifer A., Feitosa, Mary F., Duan, Qing, Schraut, Katharina E., Navarro, Pau, van Vliet-Ostaptchouk, Jana V., Zhu, Gu, Mbarek, Hamdi, Trompet, Stella, Verweij, Niek, Lyytikäinen, Leo Pekka, Deelen, Joris, Nolte, Ilja M., van der Laan, Sander W., Davies, Gail, Vermeij-Verdoold, Andrea J.M., van Oosterhout, Andy A.L.J., Vergeer-Drop, Jeannette M., Arking, Dan E., Trochet, Holly, Medina-Gomez, Carolina, Rivadeneira, Fernando, Uitterlinden, Andre G., Dehghan, Abbas, Franco, Oscar H., Sijbrands, Eric J., Hofman, Albert, White, Charles C., Mychaleckyj, Josyf C., Peloso, Gina M., Swertz, Morris A., Willemsen, Gonneke, de Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W.J.H., Ford, Ian, Buckley, Brendan M., de Craen, Anton J.M., Starr, John M., Deary, Ian J., Pasterkamp, Gerard, Generation Scotland, LifeLines Cohort Study, and CHARGE Lipids Working Group
Published: 2015

9. Fasting Glucose and the Risk of Depressive Symptoms: Instrumental-Variable Regression in the Cardiovascular Risk in Young Finns Study.

Author: Wesołowska, Karolina, Elovainio, Marko, Hintsa, Taina, Jokela, Markus, Pulkki-Råback, Laura, Pitkänen, Niina, Lipsanen, Jari, Tukiainen, Janne, Lyytikäinen, Leo-Pekka, Lehtimäki, Terho, Juonala, Markus, Raitakari, Olli, and Keltikangas-Järvinen, Liisa
Subjects: CARDIOVASCULAR diseases risk factors, MENTAL depression, GLUCOSE, REGRESSION analysis
Abstract: Purpose: Type 2 diabetes (T2D) has been associated with depressive symptoms, but the causal direction of this association and the underlying mechanisms, such as increased glucose levels, remain unclear. We used instrumental-variable regression with a genetic instrument (Mendelian randomization) to examine a causal role of increased glucose concentrations in the development of depressive symptoms. Method: Data were from the population-based Cardiovascular Risk in Young Finns Study ( n = 1217). Depressive symptoms were assessed in 2012 using a modified Beck Depression Inventory (BDI-I). Fasting glucose was measured concurrently with depressive symptoms. A genetic risk score for fasting glucose (with 35 single nucleotide polymorphisms) was used as an instrumental variable for glucose. Results: Glucose was not associated with depressive symptoms in the standard linear regression ( B = −0.04, 95% CI [−0.12, 0.04], p = .34), but the instrumental-variable regression showed an inverse association between glucose and depressive symptoms ( B = −0.43, 95% CI [−0.79, −0.07], p = .020). The difference between the estimates of standard linear regression and instrumental-variable regression was significant ( p = .026) Conclusion: Our results suggest that the association between T2D and depressive symptoms is unlikely to be caused by increased glucose concentrations. It seems possible that T2D might be linked to depressive symptoms due to low glucose levels. [ABSTRACT FROM AUTHOR]
Published: 2017
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10. Genome-wide associations for birth weight and correlations with adult disease.

Author: Horikoshi, Momoko, Beaumont, Robin N., Day, Felix R., Warrington, Nicole M., Kooijman, Marjolein N., Fernandez-Tajes, Juan, Feenstra, Bjarke, van Zuydam, Natalie R., Gaulton, Kyle J., Grarup, Niels, Bradfield, Jonathan P., Strachan, David P., Li-Gao, Ruifang, Ahluwalia, Tarunveer S., Kreiner, Eskil, Rueedi, Rico, Lyytikäinen, Leo-Pekka, Cousminer, Diana L., Wu, Ying, and Thiering, Elisabeth
Abstract: Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10−8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = −0.22, P = 5.5 × 10−13), T2D (Rg = −0.27, P = 1.1 × 10−6) and coronary artery disease (Rg = −0.30, P = 6.5 × 10−9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10−4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated. [ABSTRACT FROM AUTHOR]
Published: 2016
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11. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

Author: Loh, Marie, Zhang, Weihua, Saleheen, Danish, Wahl, Simone, Tan, Sian-Tsung, Scott, William R, Afzal, Uzma, Ahluwalia, Tarunveer S, Esko, Tõnu, Harris, Sarah E, Hartiala, Jaana, Khor, Chiea-Chuen, Stewart, Alexandre F R, Wu, Jer-Yuarn, Zhang, Yi, Lyytikäinen, Leo-Pekka, Postmus, Iris, Raitakari, Olli T, Traglia, Michela, and Barroso, Inês
Subjects: HYPERTENSION risk factors, SOUTH Asians, DNA methylation, GENEALOGY, LINKAGE disequilibrium, DISEASES
Abstract: We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation. [ABSTRACT FROM AUTHOR]
Published: 2015
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12. A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure.

Author: Turpeinen, Hannu, Seppälä, Ilkka, Lyytikäinen, Leo-Pekka, Raitoharju, Emma, Hutri-Kähönen, Nina, Levula, Mari, Oksala, Niku, Waldenberger, Melanie, Klopp, Norman, Illig, Thomas, Mononen, Nina, Laaksonen, Reijo, Raitakari, Olli, Kähönen, Mika, Lehtimäki, Terho, and Pesu, Marko
Subjects: PROPROTEIN convertases, SUBTILISINS, REGULATOR genes, BLOOD pressure, LOCUS (Genetics), GENE expression, MESSENGER RNA, SINGLE nucleotide polymorphisms
Abstract: Proprotein convertase subtilisin/kexin (PCSK) enzymes cleave and convert their immature substrates into biologically active forms. Polymorphisms in the PCSK genes have been reported to associate with human diseases and phenotypes, including hypercholesterolemia and blood pressure (BP), and targeting PCSKs is considered a promising future form of drug therapy. PCSK processing is readily induced upon upregulation of the enzyme, but the genetic factors contributing to PCSK expression have not been thoroughly characterized. To gain a comprehensive understanding of the genetic regulation of PCSK expression, we performed, for the first time, a genome-wide expression quantitative trait loci (eQTL) analysis using mRNA expression in >1400 human peripheral blood samples from the Cardiovascular Risk in Young Finns Study and ca. ten million single-nucleotide polymorphisms (SNPs). The expression data showed clear expression for FURIN, PCSK5, PCSK7 and MBTPS1 (membrane-bound transcription factor peptidase, site 1) mRNAs in virtually all tested samples. A discovery analysis demonstrated a genome-wide significant ( p < 5 × 10) association with the selected PCSK probes for 1024 variants, which were located at ten independent loci. Of these loci, 5/10 could be confirmed to regulate PCSK expression in two additional and independent sample sets. Finally, a phenotypic analysis demonstrated that a novel cis-eQTL SNP rs4702 for FURIN is strongly associated with both diastolic ( p = 0.012) and systolic ( p = 0.035) BP levels, as well as peripheral vascular resistance ( p = 0.003). These findings indicate that the expression of the PCSK enzymes is regulated by genetic factors, which have biological roles in health and disease. [ABSTRACT FROM AUTHOR]
Published: 2015
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13. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque.

Author: Yue-Mei Fan, Hernesniemi, Jussi, Oksala, Niku, Levula, Mari, Raitoharju, Emma, Collings, Auni, Hutri-Kähönen, Nina, Juonala, Markus, Marniemi, Jukka, Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Mennander, Ari, Tarkka, Matti, Kangas, Antti J., Soininen, Pasi, Salenius, Juha Pekka, Klopp, Norman, Illig, Thomas, Laitinen, Tomi, and Ala-Korpela, Mika
Subjects: TRANSCRIPTION factors, LIPOPROTEINS, METABOLISM, ATHEROSCLEROTIC plaque, ATHEROSCLEROSIS, LIPIDS, MESSENGER RNA
Abstract: Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT
Published: 2014
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14. Serotonin receptor 1B genotype and hostility, anger and aggressive behavior through the lifespan: the Young Finns study.

Author: Hakulinen, Christian, Jokela, Markus, Hintsanen, Mirka, Merjonen, Päivi, Pulkki-Råback, Laura, Seppälä, Ilkka, Lyytikäinen, Leo-Pekka, Lehtimäki, Terho, Kähönen, Mika, Viikari, Jorma, Raitakari, Olli T., and Keltikangas-Järvinen, Liisa
Subjects: GENETICS of aggression, CELL receptors, ANGER, CHI-squared test, GENES, HUMAN life cycle, LONGITUDINAL method, REGRESSION analysis, RESEARCH funding, STATISTICAL sampling, SEROTONIN, STATISTICAL models, DESCRIPTIVE statistics, GENETICS, CELL physiology
Abstract: The serotonin system has been shown to be involved in the regulation of hostility, anger, and aggressive behavior. Previous molecular genetic studies suggest that the serotonin receptor 1B (HTR1B) rs6296 genotype might have a particular role in these types of behaviors. We examined whether HTR1B is related to hostility, anger, and aggressive behavior phenotypes over a lifespan and whether it modifies the connection between childhood aggressive behavior and adulthood hostility and anger. The participants were 967 women and men from a large population based sample (The Young Finns Study) with a 27-year follow-up. Childhood aggressive behavior was reported by the mother twice when the participants were 3 to 12 years of age. Adulthood hostility and anger were self-reported by the participants between ages 24 and 36. Childhood aggressive behavior predicted adulthood hostility over 27 years. HTR1B SNP rs6296 was associated with childhood aggressive behavior but not with adulthood anger or hostility. The HTR1B SNP rs6296 modified the association between childhood aggressive behavior and adulthood hostility. Aggressive behavior and hostility might form a life course pattern, and the HTR1B might contribute to a development of this pattern. [ABSTRACT FROM AUTHOR]
Published: 2013
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15. Genome-wide association study identifies multiple loci influencing human serum metabolite levels.

Author: Kettunen, Johannes, Tukiainen, Taru, Sarin, Antti-Pekka, Ortega-Alonso, Alfredo, Tikkanen, Emmi, Lyytikäinen, Leo-Pekka, Kangas, Antti J, Soininen, Pasi, Würtz, Peter, Silander, Kaisa, Dick, Danielle M, Rose, Richard J, Savolainen, Markku J, Viikari, Jorma, Kähönen, Mika, Lehtimäki, Terho, Pietiläinen, Kirsi H, Inouye, Michael, McCarthy, Mark I, and Jula, Antti
Subjects: NUCLEAR magnetic resonance, METABOLIC disorders, PHENOTYPES, METABOLITES, HERITABILITY, SERUM
Abstract: Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P < 2.31 × 10?10) at 31 loci, including 11 for which there have not been previous reports of associations to a metabolic trait or disorder. Analyses of Finnish twin pairs suggested that the metabolic measures reported here show higher heritability than comparable conventional metabolic phenotypes. In accordance with our expectations, SNPs at the 31 loci associated with individual metabolites account for a greater proportion of the genetic component of trait variance (up to 40%) than is typically observed for conventional serum metabolic phenotypes. The identification of such associations may provide substantial insight into cardiometabolic disorders. [ABSTRACT FROM AUTHOR]
Published: 2012
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16. EEG SOURCES OF NOISE IN INTRAOPERATIVE SOMATOSENSORY EVOKED POTENTIAL MONITORING DURING PROPOFOL ANESTHESIA.

Author: Joutsen, Atte, Puumala, Pasi, Lyytikäinen, Leo-Pekka, Pajulo, Olli, Etelämäki, Aira, Eskola, Hannu, and Jäntti, Ville
Abstract: Objective. It was hypothesized that somatosensory evoked potentials can be achieved faster by selective averaging during periods of low spontaneous electroencephalographic (EEG) activity. We analyzed the components of EEG that decrease the signal-to-noise ratio of somatosensory evoked potential (SEP) recordings during propofol anesthesia. Methods. Patient EEGs were recorded with a high sampling frequency during deep anesthesia, when EEGs were in burst suppression. EEGs were segmented visually into bursts, spindles, suppressions, and artifacts. Tibial somatosensory evoked potentials (tSEPs) were averaged offline separately for burst, suppression, and spindle segments using a signal bandwidth of 30-200 Hz. Averages achieved with 2, 4, 8, 16, 64, 128, and 256 responses were compared both visually, and by calculating the signal-to-noise ratios. Results. During bursts and spindles, the noise levels were similar and significantly higher than during suppressions. Four to eight times more responses had to be averaged during bursts and spindles than during suppressions in order to achieve a similar response quality. Averaging selectively during suppressions can therefore yield reliable tSEPs in approximately one-fifth of the time required during bursts. Conclusion. The major source of EEG noise in tSEP recordings is the mixed frequency activity of the slow waves of bursts that occur during propofol anesthesia. Spindles also have frequency components that increase noise levels, but these are less important, as the number of spindles is fewer. The fastest way to obtain reliable tSEPs is by averaging selectively during suppressions. [ABSTRACT FROM AUTHOR]
Published: 2009
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17. Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Author: Bentley, Amy R, Sung, Yun J, Brown, Michael R, Winkler, Thomas W, Kraja, Aldi T, Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M, Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Hung, Yi-Jen, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Leander, Karin, Lin, Keng-Hung, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Prins, Bram, Riaz, Muhammad, Robino, Antonietta, Said, M Abdullah, Schupf, Nicole, Scott, Robert A, Sofer, Tamar, Stancáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, Van Der Most, Peter J, Varga, Tibor V, Wang, Tzung-Dau, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Xiang, Yong-Bing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Adeyemo, Adebowale, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Arzumanyan, Zorayr, Aung, Tin, Ballantyne, Christie, Barr, R Graham, Bielak, Lawrence F, Boerwinkle, Eric, Bottinger, Erwin P, Broeckel, Ulrich, Brown, Morris, Cade, Brian E, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Christensen, Kaare, COGENT-Kidney Consortium, Concas, Maria Pina, Connell, John M, De Las Fuentes, Lisa, De Silva, H Janaka, De Vries, Paul S, Doumatey, Ayo, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Floyd, James S, Forouhi, Nita G, Forrester, Terrence, Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gharib, Sina A, Gigante, Bruna, Giulianini, Franco, Grabe, Hans J, Gu, C Charles, Harris, Tamara B, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E, Ikram, M Arfan, EPIC-InterAct Consortium, Jia, Yucheng, Joehanes, Roby, Johnson, Craig, Jonas, Jost Bruno, Justice, Anne E, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E, Kritchevsky, Stephen B, Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lehne, Benjamin, Lewis, Cora E, Li, Yize, Liang, Jingjing, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Kiang, Loh, Marie, Lohman, Kurt K, Louie, Tin, Luzzi, Anna, Mägi, Reedik, Mahajan, Anubha, Manichaikul, Ani W, McKenzie, Colin A, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L, Momozawa, Yukihide, Morris, Andrew P, Murray, Alison D, Nalls, Mike A, Nauck, Matthias, Nelson, Christopher P, North, Kari E, O'Connell, Jeffrey R, Palmer, Nicholette D, Papanicolau, George J, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Polasek, Ozren, Poulter, Neil, Raitakari, Olli T, Reiner, Alex P, Renström, Frida, Rice, Treva K, Rich, Stephen S, Robinson, Jennifer G, Rose, Lynda M, Rosendaal, Frits R, Rudan, Igor, Schmidt, Carsten O, Schreiner, Pamela J, Scott, William R, Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Jennifer A, Snieder, Harold, Starr, John M, Strauch, Konstantin, Stringham, Heather M, Tan, Nicholas YQ, Tang, Hua, Taylor, Kent D, Teo, Yik Ying, Tham, Yih Chung, Tiemeier, Henning, Turner, Stephen T, Uitterlinden, André G, Understanding Society Scientific Group, Van Heemst, Diana, Waldenberger, Melanie, Wang, Heming, Wang, Lan, Wang, Lihua, Wei, Wen Bin, Williams, Christine A, Wilson, Gregory, Wojczynski, Mary K, Yao, Jie, Young, Kristin, Yu, Caizheng, Yuan, Jian-Min, Zhou, Jie, Zonderman, Alan B, Becker, Diane M, Boehnke, Michael, Bowden, Donald W, Chambers, John C, Cooper, Richard S, De Faire, Ulf, Deary, Ian J, Elliott, Paul, Esko, Tõnu, Farrall, Martin, Franks, Paul W, Freedman, Barry I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L, Juang, Jyh-Ming Jimmy, Kamatani, Yoichiro, Kammerer, Candace M, Kato, Norihiro, Kooner, Jaspal S, Laakso, Markku, Laurie, Cathy C, Lee, I-Te, Lehtimäki, Terho, Lifelines Cohort, Magnusson, Patrik KE, Oldehinkel, Albertine J, Penninx, Brenda WJH, Pereira, Alexandre C, Rauramaa, Rainer, Redline, Susan, Samani, Nilesh J, Scott, James, Shu, Xiao-Ou, Van Der Harst, Pim, Wagenknecht, Lynne E, Wang, Jun-Sing, Wang, Ya Xing, Wareham, Nicholas J, Watkins, Hugh, Weir, David R, Wickremasinghe, Ananda R, Wu, Tangchun, Zeggini, Eleftheria, Zheng, Wei, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Kardia, Sharon LR, Liu, Yongmei, Psaty, Bruce M, Ridker, Paul M, Van Dam, Rob M, Mook-Kanamori, Dennis O, Fornage, Myriam, Province, Michael A, Kelly, Tanika N, Fox, Ervin R, Hayward, Caroline, Van Duijn, Cornelia M, Tai, E Shyong, Wong, Tien Yin, Loos, Ruth JF, Franceschini, Nora, Rotter, Jerome I, Zhu, Xiaofeng, Bierut, Laura J, Gauderman, W James, Rice, Kenneth, Munroe, Patricia B, Morrison, Alanna C, Rao, Dabeeru C, Rotimi, Charles N, and Cupples, L Adrienne
Subjects: Adult, Aged, 80 and over, Male, Adolescent, Genotype, Smoking, Middle Aged, Lipids, Linkage Disequilibrium, 3. Good health, Young Adult, Humans, Female, Life Style, Aged, Genome-Wide Association Study
Abstract: The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

18. Pro-opiomelanocortin and its Processing Enzymes Associate with Plaque Stability in Human Atherosclerosis - Tampere Vascular Study.

Author: Rinne, Petteri, Lyytikäinen, Leo-Pekka, Raitoharju, Emma, Kadiri, James J., Kholova, Ivana, Kähönen, Mika, Lehtimäki, Terho, and Oksala, Niku
Abstract: α-melanocyte-stimulating hormone (α-MSH) is processed from pro-opiomelanocortin (POMC) and mediates anti-inflammatory actions in leukocytes. α-MSH also promotes macrophage reverse cholesterol transport by inducing ATP-binding cassette transporters ABCA1 and ABCG1. Here we investigated the regulation of POMC and α-MSH expression in atherosclerosis. First, transcript levels of POMC and its processing enzymes were analyzed in human arterial plaques (n = 68) and non-atherosclerotic controls (n = 24) as well as in whole blood samples from coronary artery disease patients (n = 55) and controls (n = 45) by microarray. POMC expression was increased in femoral plaques compared to control samples as well as in unstable advanced plaques. α-MSH-producing enzyme, carboxypeptidase E, was down-regulated, whereas prolylcarboxypeptidase, an enzyme inactivating α-MSH, was up-regulated in unstable plaques compared to stable plaques, suggesting a possible reduction in intraplaque α-MSH levels. Second, immunohistochemical analyses revealed the presence of α-MSH in atherosclerotic plaques and its localization in macrophages and other cell types. Lastly, supporting the role of α-MSH in reverse cholesterol transport, POMC expression correlated with ABCA1 and ABCG1 in human plaque and whole blood samples. In conclusion, α-MSH is expressed in atherosclerotic plaques and its processing enzymes associate with plaque stability, suggesting that measures to enhance the local bioavailability of α-MSH might protect against atherosclerosis. [ABSTRACT FROM AUTHOR]
Published: 2018
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19. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.

Author: van Setten, Jessica, Brody, Jennifer A., Jamshidi, Yalda, Swenson, Brenton R., Butler, Anne M., Campbell, Harry, Del Greco, Fabiola M., Evans, Daniel S., Gibson, Quince, Gudbjartsson, Daniel F., Kerr, Kathleen F., Krijthe, Bouwe P., Lyytikäinen, Leo-Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M., Padmanabhan, Sandosh, Ritchie, Marylyn D., Robino, Antonietta, and Smith, Albert V.
Abstract: Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development. Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation. [ABSTRACT FROM AUTHOR]
Published: 2018
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20. Differentially expressed genes and canonical pathway expression in human atherosclerotic plaques - Tampere Vascular Study.

Author: Sulkava, Miska, Raitoharju, Emma, Levula, Mari, Seppälä, Ilkka, Lyytikäinen, Leo-Pekka, Mennander, Ari, Järvinen, Otso, Zeitlin, Rainer, Salenius, Juha-Pekka, Illig, Thomas, Klopp, Norman, Mononen, Nina, Laaksonen, Reijo, Kähönen, Mika, Oksala, Niku, and Lehtimäki, Terho
Abstract: Cardiovascular diseases due to atherosclerosis are the leading cause of death globally. We aimed to investigate the potentially altered gene and pathway expression in advanced peripheral atherosclerotic plaques in comparison to healthy control arteries. Gene expression analysis was performed (Illumina HumanHT-12 version 3 Expression BeadChip) for 68 advanced atherosclerotic plaques (15 aortic, 29 carotid and 24 femoral plaques) and 28 controls (left internal thoracic artery (LITA)) from Tampere Vascular Study. Dysregulation of individual genes was compared to healthy controls and between plaques from different arterial beds and Ingenuity pathway analysis was conducted on genes with a fold change (FC) > ±1.5 and false discovery rate (FDR) < 0.05. 787 genes were significantly differentially expressed in atherosclerotic plaques. The most up-regulated genes were osteopontin and multiple MMPs, and the most down-regulated were cell death-inducing DFFA-like effector C and A (CIDEC, CIDEA) and apolipoprotein D (FC > 20). 156 pathways were differentially expressed in atherosclerotic plaques, mostly inflammation-related, especially related with leukocyte trafficking and signaling. In artery specific plaque analysis 50.4% of canonical pathways and 41.2% GO terms differentially expressed were in common for all three arterial beds. Our results confirm the inflammatory nature of advanced atherosclerosis and show novel pathway differences between different arterial beds. [ABSTRACT FROM AUTHOR]
Published: 2017
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21. Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism-The Young Finns Study.

Author: Raitoharju, Emma, Seppälä, Ilkka, Lyytikäinen, Leo-Pekka, Viikari, Jorma, Ala-Korpela, Mika, Soininen, Pasi, Kangas, Antti J., Waldenberger, Melanie, Klopp, Norman, Illig, Thomas, Leiviskä, Jaana, Loo, Britt-Marie, Oksala, Niku, Kähönen, Mika, Hutri-Kähönen, Nina, Laaksonen, Reijo, Raitakari, Olli, and Lehtimäki, Terho
Abstract: MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34-49 years (n = 871). Liver fat status was assessed ultrasonographically. Levels of hsa-miR-122-5p and -885-5p were up-regulated in individuals with FL (fold change (FC) = 1.55, p = 1.36 * 10−14 and FC = 1.25, p = 4.86 * 10−4, respectively). In regression model adjusted with age, sex and BMI, hsa-miR-122-5p and -885-5p predicted FL (OR = 2.07, p = 1.29 * 10−8 and OR = 1.41, p = 0.002, respectively). Together hsa-miR-122-5p and -885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels associated with small VLDL, IDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels associated inversely with XL HDL cholesterol levels. Hsa-miR-885-5p levels correlated inversely with oxysterol-binding protein 2 (OSBPL2) expression (r = −0.143, p = 1.00 * 10−4) and suppressing the expression of this lipid receptor and sterol transporter could link hsa-miR-885-5p with HDL cholesterol levels. [ABSTRACT FROM AUTHOR]
Published: 2016
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22. No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.

Author: Loley, Christina, Alver, Maris, Assimes, Themistocles L., Bjonnes, Andrew, Goel, Anuj, Gustafsson, Stefan, Hernesniemi, Jussi, Hopewell, Jemma C., Kanoni, Stavroula, Kleber, Marcus E., Lau, King Wai, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Nelson, Christopher P., Nikpay, Majid, Qu, Liming, Salfati, Elias, Scholz, Markus, Tukiainen, Taru, and Willenborg, Christina
Published: 2016
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23. Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke.

Author: Seppälä, Ilkka, Kleber, Marcus E., Bevan, Steve, Lyytikäinen, Leo-Pekka, Oksala, Niku, Hernesniemi, Jussi A., Mäkelä, Kari-Matti, Rothwell, Peter M., Sudlow, Cathie, Dichgans, Martin, Mononen, Nina, Vlachopoulou, Efthymia, Sinisalo, Juha, Delgado, Graciela E., Laaksonen, Reijo, Koskinen, Tuomas, Scharnagl, Hubert, Kähönen, Mika, Markus, Hugh S., and März, Winfried
Published: 2016
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24. Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.

Author: Kettunen, Johannes, Demirkan, Ayşe, Würtz, Peter, Draisma, Harmen H.M., Haller, Toomas, Rawal, Rajesh, Vaarhorst, Anika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Pirinen, Matti, Pool, René, Sarin, Antti-Pekka, Soininen, Pasi, Tukiainen, Taru, Wang, Qin, Tiainen, Mika, Tynkkynen, Tuulia, Amin, Najaf, Zeller, Tanja, and Beekman, Marian
Published: 2016
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25. Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2.

Author: Ware, Jennifer J., Chen, Xiangning, Vink, Jacqueline, Loukola, Anu, Minica, Camelia, Pool, Rene, Milaneschi, Yuri, Mangino, Massimo, Menni, Cristina, Chen, Jingchun, Peterson, Roseann E., Auro, Kirsi, Lyytikäinen, Leo-Pekka, Wedenoja, Juho, Stiby, Alexander I., Hemani, Gibran, Willemsen, Gonneke, Hottenga, Jouke Jan, Korhonen, Tellervo, and Heliövaara, Markku
Published: 2016
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26. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Author: Kilpeläinen, Tuomas O., Carli, Jayne F. Martin, Skowronski, Alicja A., Sun, Qi, Kriebel, Jennifer, Feitosa, Mary F, Hedman, Åsa K., Drong, Alexander W., Hayes, James E., Zhao, Jinghua, Pers, Tune H., Schick, Ursula, Grarup, Niels, Kutalik, Zoltán, Trompet, Stella, Mangino, Massimo, Kristiansson, Kati, Beekman, Marian, Lyytikäinen, Leo-Pekka, and Eriksson, Joel
Published: 2016
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27. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author: Alison Pattie, Ailith Pirie, Francis S. Collins, Charles Kooperberg, Nienke van Leeuwen, Carmel Moore, Sharon L.R. Kardia, Neil R. Robertson, Lisa Bastarache, Allan Linneberg, Peter T. Campbell, Helena Kuivaniemi, Struan F.A. Grant, Sascha Fauser, Sekar Kathiresan, Lars Lind, Erin B. Ware, Olli T. Raitakari, Dawn M. Waterworth, James G. Wilson, Markus Perola, Chris J. Packard, Michelle L. O'Donoghue, Fredrik Karpe, Roel A. Ophoff, Sailaja Vedantam, Artitaya Lophatananon, Uwe Völker, Emmanouil Tsafantakis, Hakon Hakonarson, Dajiang J. Liu, Craig E. Pennell, Xueling Sim, Jennifer E. Huffman, Sandosh Padmanabhan, Digna R. Velez Edwards, Michiel L. Bots, Ayush Giri, Renée de Mutsert, Emanuele Di Angelantonio, Nicholas J. Wareham, Jin Li, Gail P. Jarvik, Evangelos Evangelou, Anne Tybjærg-Hansen, Patricia B. Munroe, Penny Gordon-Larsen, Lia E. Bang, Ivan Brandslund, Hester M. den Ruijter, Jussi Hernesniemi, Nancy L. Heard-Costa, Angela L. Mazul, Jonathan Tyrer, Danish Saleheen, Mark J. Caulfield, John Andrew Pospisilik, Annette Peters, Caroline Hayward, Iris M. Heid, J. Wouter Jukema, Valérie Turcot, Matt Neville, Rudolf Uher, Patricia A. Peyser, Jessica D. Faul, Asif Rasheed, Shuai Wang, John C. Chambers, Jordi Corominas Galbany, Murray H. Brilliant, Yucheng Jia, Torben Hansen, Veikko Salomaa, Mary F. Feitosa, Mathias Gorski, Li-An Lin, George Dedoussis, Honghuang Lin, Ethan M. Lange, Veronique Vitart, Bratati Kahali, Alexander Teumer, Jerome I. Rotter, Wayne H-H Sheu, Vilmantas Giedraitis, Aliki-Eleni Farmaki, Lorraine Southam, Ele Ferrannini, Anette P. Gjesing, Krina T. Zondervan, Stavroula Kanoni, David J. Roberts, Rebecca S. Fine, Svati H. Shah, Tugce Karaderi, Claudia Langenberg, Stefan Johansson, Elizabeth K. Speliotes, Alexander P. Reiner, Ching-Ti Liu, Yiqin Wang, Pål R. Njølstad, Gabriel Cuellar-Partida, Amanda J. Cox, Tim D. Spector, Paul W. Franks, Anke Tönjes, John D. Rioux, Jeffrey Haessler, Paul L. Auer, Ingrid B. Borecki, Deborah J. Thompson, Weihua Zhang, John R. B. Perry, Paul Elliott, Folkert W. Asselbergs, Myriam Fornage, Ken Sin Lo, Marie Moitry, Paul Mitchell, Martin den Heijer, Zoltán Kutalik, Tune H. Pers, Kari Stefansson, Kari Kuulasmaa, Robert E. Schoen, Mark C.H. De Groot, Laura M. Yerges-Armstrong, Jing Hua Zhao, Beverley Balkau, Peggy L. Peissig, Michael Boehnke, Janie Corley, Katharine R. Owen, Unnur Thorsteinsdottir, Naveed Sattar, Sita H. Vermeulen, Thomas N. Person, Mark I. McCarthy, Paul I.W. de Bakker, David Lamparter, Poorva Mudgal, Nicholette D. Palmer, Maria Karaleftheri, Jan-Håkan Jansson, Ozren Polasek, Ruth J. F. Loos, Daniel R. Witte, Dermot F. Reilly, Anubha Mahajan, Stella Trompet, James A. Perry, Yingchang Lu, Claudia Schurmann, Yii-Der Ida Chen, Hidetoshi Kitajima, Dale R. Nyholt, John Danesh, Pamela J. Schreiner, Narisu Narisu, Jose C. Florez, Adelheid Lempradl, Gerome Breen, Torben Jørgensen, Anu Loukola, Joe Dennis, Hans-Jörgen Grabe, Vilmundur Gudnason, Timo A. Lakka, Heather M. Highland, Sven Bergmann, Marie-Pierre Dubé, Giovanni Veronesi, Martina Müller-Nurasyid, Jaakko Tuomilehto, Nele Friedrich, Joel N. Hirschhorn, Pia R. Kamstrup, Nilesh J. Samani, Josh C. Denny, Mika Kähönen, Massimiliano Cocca, Liang Sun, Karina Meidtner, Carsten A. Böger, Sara M. Willems, Marcelo P. Segura-Lepe, Johanna Kuusisto, Hanieh Yaghootkar, Konstantin Strauch, Ruth Frikke-Schmidt, Jane Gibson, Matti Uusitupa, Oscar H. Franco, Yongmei Liu, Heather M. Stringham, Rohit Varma, Grant W. Montgomery, Dennis O. Mook-Kanamori, Stefania Cappellani, Paul L. Huang, Albert V. Smith, Eric Kim, Anke R. Hammerschlag, Katherine S. Ruth, Carolina Medina-Gomez, Gerard Pasterkamp, Cristen J. Willer, Alisa K. Manning, Frida Renström, René S. Kahn, Lili Milani, Feijie Wang, Tessel E. Galesloot, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Adam S. Butterworth, Tamara B. Harris, Matthew A. Allison, Paul M. Ridker, David J. Carey, Todd L. Edwards, Panos Deloukas, Xiuqing Guo, Lawrence F. Bielak, Leena Moilanen, Heiner Boeing, Peter Kovacs, Karen L. Mohlke, Myriam Rheinberger, Cramer Christensen, Betina H. Thuesen, Mike A. Nalls, Erik Ingelsson, Nicholas G. D. Masca, Colin N. A. Palmer, Audrey E. Hendricks, Linda Broer, Vanisha Mistry, Praveen Surendran, Audrey Y. Chu, Rainer Rauramaa, Angela D'Eustacchio, Helen Griffiths, Satu Männistö, Patrick T. Ellinor, Terho Lehtimäki, Katherine E. Tansey, I. Sadaf Farooqi, Gaëlle Marenne, Anneke I. den Hollander, Jessica van Setten, Hannu Puolijoki, Tinca J. C. Polderman, Timothy M. Frayling, Niels Grarup, Eric Boerwinkle, Gonçalo R. Abecasis, Adam E. Locke, Mengmeng Du, Manuel A. Rivas, Philippe Amouyel, Jaakko Kaprio, Leslie A. Lange, Loes M. Olde Loohuis, Trevor A. Mori, Lambertus A. Kiemeney, Wei Zhao, Eva Rb Petersen, Huaixing Li, Thomas W. Winkler, Tellervo Korhonen, Kathleen Stirrups, Jean Ferrières, Wei Zhou, Ian J. Deary, Guillaume Lettre, M. Arfan Ikram, Alex W. Hewitt, Marit E. Jørgensen, Ian Ford, Liang He, Mark Walker, Stefan Gustafsson, Andre Franke, Yao Hu, Jaana Lindström, Jonathan P. Bradfield, Anne E. Justice, Kristin L. Young, Sander W. van der Laan, Shuang Feng, Yadav Sapkota, Douglas F. Easton, Cornelia M. van Duijn, Amy J. Swift, Kjell Nikus, Helen R. Warren, Christian Theil Have, Wei Gan, Steven A. Lubitz, Harvey D. White, Pirjo Komulainen, John M. Starr, Jeffrey R. O'Connel, Anette Varbo, Daniel I. Chasman, Ruifang Li-Gao, Lynne E. Wagenknecht, Matthias Blüher, Xiaowei Zhan, Thomas F. Vogt, Eleftheria Zeggini, Tamuno Alfred, Katja K.H. Aben, Lars Wallentin, Joanna M. M. Howson, Jie Yao, Eulalia Catamo, Henrik Vestergaard, Gina M. Peloso, Markku Laakso, Matthias B. Schulze, Hayato Tada, Jennifer Wessel, Andrew R. Wood, Erwin P. Bottinger, Cora E. Lewis, Robin Young, Carol A. Wang, Oddgeir L. Holmen, Andrew J. Slater, Jean-Claude Tardif, Xu Lin, Inês Barroso, Gail Davies, Tibor V. Varga, Andrew J. Lotery, Igor Rudan, Andrew T. Hattersley, Michael Stumvoll, David Ellinghaus, Andrew C. Heath, Frank Kee, Christopher P. Nelson, Donald W. Bowden, Alison M. Dunning, Marianne Benn, Oluf Pedersen, Amber A. Burt, Aniruddh P. Patel, G. Kees Hovingh, David S. Crosslin, Gorm B. Jensen, Keng-Hung Lin, Dewan S. Alam, Jian'an Luan, Ying Wu, Tõnu Esko, Kathleen Mullan Harris, Antonietta Robino, Anne U. Jackson, Eirini Marouli, Robert A. Scott, Jette Bork-Jensen, Olov Rolandsson, Nanette R. Lee, Gerard Tromp, Megan L. Grove, Suthesh Sivapalaratnam, Sameer E. Al-Harthi, Roberta McKean-Cowdin, Paolo Gasparini, Ellen W. Demerath, Marco Brumat, Maggie C.Y. Ng, Børge G. Nordestgaard, Kari E. North, Rajiv Chowdhury, Mauno Vanhala, Andrew P. Morris, Sarah E. Medland, Sune F. Nielsen, Ilaria Gandin, Øyvind Helgeland, James P. Cook, Kent D. Taylor, Andrew D. Morris, Gudmar Thorleifsson, André G. Uitterlinden, Pang Yao, Valgerdur Steinthorsdottir, Eric B. Larson, Kerrin S. Small, Cecilia M. Lindgren, Dragana Vuckovic, Mariaelisa Graff, Fotios Drenos, Jaspal S. Kooner, Schurmann, Claudia [0000-0003-4158-9192], Justice, Anne E [0000-0002-8903-8712], Giri, Ayush [0000-0002-7786-4670], Locke, Adam E [0000-0001-6227-198X], Young, Kristin L [0000-0003-0070-6145], Medina-Gomez, Carolina [0000-0001-7999-5538], Winkler, Thomas W [0000-0003-0292-5421], Zeggini, Eleftheria [0000-0003-4238-659X], Zhao, Wei [0000-0002-8301-9297], Zondervan, Krina T [0000-0002-0275-9905], Pospisilik, John A [0000-0002-9745-0977], Rivadeneira, Fernando [0000-0001-9435-9441], Deloukas, Panos [0000-0001-9251-070X], Apollo - University of Cambridge Repository, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ACS - Atherosclerosis & ischemic syndromes, Internal Medicine, Epidemiology, Obstetrics & Gynecology, Radiology & Nuclear Medicine, CHD Exome+ Consortium, EPIC-CVD Consortium, ExomeBP Consortium, Global Lipids Genetic Consortium, GoT2D Genes Consortium, EPIC InterAct Consortium, INTERVAL Study, ReproGen Consortium, T2D-Genes Consortium, MAGIC Investigators, Understanding Society Scientific Group, Biological Psychology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, British Heart Foundation, Wellcome Trust, Medical Research Council (MRC), National Institute for Health Research, Home Office, National Institutes of Health, Imperial College Healthcare NHS Trust- BRC Funding, Turcot, Valérie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Gonçalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Inê, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthia, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotio, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelo, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmanta, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathia, Grabe, Hans-Jörgen, Grant, Struan F. A., Grarup, Niel, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kee, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charle, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lar, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'An, Lubitz, Steven A., Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L., Mccarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Müller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Olde Loohuis, Loes M., Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Marku, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, Van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lar, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Pano, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., Loos, Ruth J. F., Internal medicine, AGEM - Endocrinology, metabolism and nutrition, Amsterdam Movement Sciences - Rehabilitation & Development, Amsterdam Movement Sciences - Restoration and Development, APH - Aging & Later Life, Physiology, and VU University medical center
Subjects: 0301 basic medicine, Male, ReproGen Consortium, MathematicsofComputing_GENERAL, Genome-wide association study, medicine.disease_cause, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Body Mass Index, genetics [Obesity], 0302 clinical medicine, Gene Frequency, Glucose homeostasis, Adult, Animals, Drosophila/genetics, Energy Intake/genetics, Energy Metabolism/genetics, Female, Genetic Variation, Humans, Obesity/genetics, Proteins/genetics, Syndrome, 11 Medical and Health Sciences, 2. Zero hunger, Genetics, Genetics & Heredity, Mutation, CHD Exome+ Consortium, body mass index, TheoryofComputation_GENERAL, T2D-Genes Consortium, GENOME-WIDE ASSOCIATION, MELANOCORTIN-4 RECEPTOR GENE, DONEPEZIL 23 MG, FRAMESHIFT MUTATION, GLUCOSE-HOMEOSTASIS, HYPOTHALAMIC AMPK, CODING VARIANTS, BLOOD-PRESSURE, RARE, LOCI, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Drosophila, ExomeBP Consortium, Life Sciences & Biomedicine, INTERVAL Study, Understanding Society Scientific Group, EPIC InterAct Consortium, genetics [Energy Metabolism], Biology, EPIC-CVD Consortium, Frameshift mutation, 03 medical and health sciences, MAGIC Investigators, All institutes and research themes of the Radboud University Medical Center, Genetic, SDG 3 - Good Health and Well-being, ddc:570, genetics [Drosophila], medicine, Journal Article, Global Lipids Genetic Consortium, Obesity, Gene, Allele frequency, Genetic association, Science & Technology, Proteins, 06 Biological Sciences, genetics [Proteins], Minor allele frequency, 030104 developmental biology, GoT2D Genes Consortium, Energy Intake, Energy Metabolism, genetics [Energy Intake], 030217 neurology & neurosurgery, Developmental Biology
Abstract: Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
Published: 2018

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27 results on '"Lyytikäinen, Leo-Pekka"'

1. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

2. Uncovering the complex genetic architecture of human plasma lipidome using machine learning methods.

3. C-type lectin receptor CLEC4A2 promotes tissue adaptation of macrophages and protects against atherosclerosis.

4. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways.

5. Prehospital Adenosine Diphosphate Receptor Blocker Use, Culprit Artery Flow, and Mortality in STEMI: The MADDEC Study.

6. Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health.

7. Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts.

8. Fine mapping the CETP region reveals a common intronic insertion associated to HDL-C

9. Fasting Glucose and the Risk of Depressive Symptoms: Instrumental-Variable Regression in the Cardiovascular Risk in Young Finns Study.

10. Genome-wide associations for birth weight and correlations with adult disease.

11. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

12. A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure.

13. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque.

14. Serotonin receptor 1B genotype and hostility, anger and aggressive behavior through the lifespan: the Young Finns study.

15. Genome-wide association study identifies multiple loci influencing human serum metabolite levels.

16. EEG SOURCES OF NOISE IN INTRAOPERATIVE SOMATOSENSORY EVOKED POTENTIAL MONITORING DURING PROPOFOL ANESTHESIA.

17. Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

18. Pro-opiomelanocortin and its Processing Enzymes Associate with Plaque Stability in Human Atherosclerosis - Tampere Vascular Study.

19. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.

20. Differentially expressed genes and canonical pathway expression in human atherosclerotic plaques - Tampere Vascular Study.

21. Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism-The Young Finns Study.

22. No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.

23. Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke.

24. Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.

25. Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2.

26. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

27. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

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27 results on '"Lyytikäinen, Leo-Pekka"'

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