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3. Identification of gene networks jointly associated with depressive symptoms and cardiovascular health metrics using whole blood transcriptome in the Young Finns Study

Author

Mishra, Binisha H., primary, Raitoharju, Emma, additional, Mononen, Nina, additional, Saarinen, Aino, additional, Viikari, Jorma, additional, Juonala, Markus, additional, Hutri-Kähönen, Nina, additional, Kähönen, Mika, additional, Raitakari, Olli T., additional, Lehtimäki, Terho, additional, and Mishra, Pashupati P., additional

Published
2024
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4. Genetic and environmental perturbations lead to regulatory decoherence

Author

Lea, Amanda, Subramaniam, Meena, Ko, Arthur, Lehtimäki, Terho, Raitoharju, Emma, Kähönen, Mika, Seppälä, Ilkka, Mononen, Nina, Raitakari, Olli T, Ala-Korpela, Mika, Pajukanta, Päivi, Zaitlen, Noah, and Ayroles, Julien F

Subjects
Genetics, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Computer Simulation, Environmental Exposure, Gene Expression Profiling, Genetic Variation, Humans, Individuality, Magnetic Resonance Spectroscopy, Metabolic Diseases, Metabolome, Quantitative Trait Loci, co-expression, decanalization, decoherence, genetics, genomics, human, human biology, medicine, metabolic syndrome, Biochemistry and Cell Biology
Abstract

Correlation among traits is a fundamental feature of biological systems that remains difficult to study. To address this problem, we developed a flexible approach that allows us to identify factors associated with inter-individual variation in correlation. We use data from three human cohorts to study the effects of genetic and environmental variation on correlations among mRNA transcripts and among NMR metabolites. We first show that environmental exposures (infection and disease) lead to a systematic loss of correlation, which we define as 'decoherence'. Using longitudinal data, we show that decoherent metabolites are better predictors of whether someone will develop metabolic syndrome than metabolites commonly used as biomarkers of this disease. Finally, we demonstrate that correlation itself is under genetic control by mapping hundreds of 'correlation quantitative trait loci (QTLs)'. Together, this work furthers our understanding of how and why coordinated biological processes break down, and points to a potential role for decoherence in disease.Editorial noteThis article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Published
2019

6. Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Author

Eicher, John D, Chami, Nathalie, Kacprowski, Tim, Nomura, Akihiro, Chen, Ming-Huei, Yanek, Lisa R, Tajuddin, Salman M, Schick, Ursula M, Slater, Andrew J, Pankratz, Nathan, Polfus, Linda, Schurmann, Claudia, Giri, Ayush, Brody, Jennifer A, Lange, Leslie A, Manichaikul, Ani, Hill, W David, Pazoki, Raha, Elliot, Paul, Evangelou, Evangelos, Tzoulaki, Ioanna, Gao, He, Vergnaud, Anne-Claire, Mathias, Rasika A, Becker, Diane M, Becker, Lewis C, Burt, Amber, Crosslin, David R, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Hernesniemi, Jussi, Kähönen, Mika, Raitoharju, Emma, Mononen, Nina, Raitakari, Olli T, Lehtimäki, Terho, Cushman, Mary, Zakai, Neil A, Nickerson, Deborah A, Raffield, Laura M, Quarells, Rakale, Willer, Cristen J, Peloso, Gina M, Abecasis, Goncalo R, Liu, Dajiang J, Consortium, Global Lipids Genetics, Deloukas, Panos, Samani, Nilesh J, Schunkert, Heribert, Erdmann, Jeanette, Consortium, CARDIoGRAM Exome, Consortium, Myocardial Infarction Genetics, Fornage, Myriam, Richard, Melissa, Tardif, Jean-Claude, Rioux, John D, Dube, Marie-Pierre, de Denus, Simon, Lu, Yingchang, Bottinger, Erwin P, Loos, Ruth JF, Smith, Albert Vernon, Harris, Tamara B, Launer, Lenore J, Gudnason, Vilmundur, Edwards, Digna R Velez, Torstenson, Eric S, Liu, Yongmei, Tracy, Russell P, Rotter, Jerome I, Rich, Stephen S, Highland, Heather M, Boerwinkle, Eric, Li, Jin, Lange, Ethan, Wilson, James G, Mihailov, Evelin, Mägi, Reedik, Hirschhorn, Joel, Metspalu, Andres, Esko, Tõnu, Vacchi-Suzzi, Caterina, Nalls, Mike A, Zonderman, Alan B, Evans, Michele K, Engström, Gunnar, Orho-Melander, Marju, Melander, Olle, O’Donoghue, Michelle L, Waterworth, Dawn M, Wallentin, Lars, White, Harvey D, Floyd, James S, Bartz, Traci M, Rice, Kenneth M, Psaty, Bruce M, Starr, JM, Liewald, David CM, Hayward, Caroline, and Deary, Ian J

Subjects
Genetics, Cardiovascular, Hematology, 1.1 Normal biological development and functioning, Underpinning research, Blood, Blood Platelets, Exome, Female, Genetic Variation, Genome-Wide Association Study, Humans, Male, Mean Platelet Volume, Platelet Count, Global Lipids Genetics Consortium, CARDIoGRAM Exome Consortium, Myocardial Infarction Genetics Consortium, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.

Published
2016

7. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

Author

Chami, Nathalie, Chen, Ming-Huei, Slater, Andrew J, Eicher, John D, Evangelou, Evangelos, Tajuddin, Salman M, Love-Gregory, Latisha, Kacprowski, Tim, Schick, Ursula M, Nomura, Akihiro, Giri, Ayush, Lessard, Samuel, Brody, Jennifer A, Schurmann, Claudia, Pankratz, Nathan, Yanek, Lisa R, Manichaikul, Ani, Pazoki, Raha, Mihailov, Evelin, Hill, W David, Raffield, Laura M, Burt, Amber, Bartz, Traci M, Becker, Diane M, Becker, Lewis C, Boerwinkle, Eric, Bork-Jensen, Jette, Bottinger, Erwin P, O’Donoghue, Michelle L, Crosslin, David R, de Denus, Simon, Dubé, Marie-Pierre, Elliott, Paul, Engström, Gunnar, Evans, Michele K, Floyd, James S, Fornage, Myriam, Gao, He, Greinacher, Andreas, Gudnason, Vilmundur, Hansen, Torben, Harris, Tamara B, Hayward, Caroline, Hernesniemi, Jussi, Highland, Heather M, Hirschhorn, Joel N, Hofman, Albert, Irvin, Marguerite R, Kähönen, Mika, Lange, Ethan, Launer, Lenore J, Lehtimäki, Terho, Li, Jin, Liewald, David CM, Linneberg, Allan, Liu, Yongmei, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mägi, Reedik, Mathias, Rasika A, Melander, Olle, Metspalu, Andres, Mononen, Nina, Nalls, Mike A, Nickerson, Deborah A, Nikus, Kjell, O’Donnell, Chris J, Orho-Melander, Marju, Pedersen, Oluf, Petersmann, Astrid, Polfus, Linda, Psaty, Bruce M, Raitakari, Olli T, Raitoharju, Emma, Richard, Melissa, Rice, Kenneth M, Rivadeneira, Fernando, Rotter, Jerome I, Schmidt, Frank, Smith, Albert Vernon, Starr, John M, Taylor, Kent D, Teumer, Alexander, Thuesen, Betina H, Torstenson, Eric S, Tracy, Russell P, Tzoulaki, Ioanna, Zakai, Neil A, Vacchi-Suzzi, Caterina, van Duijn, Cornelia M, van Rooij, Frank JA, Cushman, Mary, Deary, Ian J, Edwards, Digna R Velez, Vergnaud, Anne-Claire, Wallentin, Lars, Waterworth, Dawn M, White, Harvey D, Wilson, James G, and Zonderman, Alan B

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Rare Diseases, Hematology, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Black or African American, Allelic Imbalance, Erythrocyte Indices, Erythrocytes, Erythropoiesis, Exome, Gene Frequency, Genetic Pleiotropy, Genetic Variation, Genotype, Hematocrit, Hemoglobins, Humans, Quantitative Trait Loci, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 × 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 × 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 × 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.

Published
2016

8. Integrative approaches for large-scale transcriptome-wide association studies

Author

Gusev, Alexander, Ko, Arthur, Shi, Huwenbo, Bhatia, Gaurav, Chung, Wonil, Penninx, Brenda WJH, Jansen, Rick, de Geus, Eco JC, Boomsma, Dorret I, Wright, Fred A, Sullivan, Patrick F, Nikkola, Elina, Alvarez, Marcus, Civelek, Mete, Lusis, Aldons J, Lehtimäki, Terho, Raitoharju, Emma, Kähönen, Mika, Seppälä, Ilkka, Raitakari, Olli T, Kuusisto, Johanna, Laakso, Markku, Price, Alkes L, Pajukanta, Päivi, and Pasaniuc, Bogdan

Subjects
Biological Sciences, Genetics, Biotechnology, Obesity, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Cancer, Animals, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Mice, Phenotype, Quantitative Trait Loci, Transcriptome, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance of one or multiple proteins. Here we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated with complex traits. We leverage expression imputation from genetic data to perform a transcriptome-wide association study (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ∼ 3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 new genes significantly associated with obesity-related traits (BMI, lipids and height). Many of these genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits.

Published
2016

13. Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs

Author

Marttila, Saara, Viiri, Leena E., Mishra, Pashupati P., Kühnel, Brigitte, Matias-Garcia, Pamela R., Lyytikäinen, Leo-Pekka, Ceder, Tiina, Mononen, Nina, Rathmann, Wolfgang, Winkelmann, Juliane, Peters, Annette, Kähönen, Mika, Hutri-Kähönen, Nina, Juonala, Markus, Aalto-Setälä, Katriina, Raitakari, Olli, Lehtimäki, Terho, Waldenberger, Melanie, and Raitoharju, Emma

Published
2021
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14. Polygenic risk for schizophrenia, social dispositions, and pace of epigenetic aging: Results from the Young Finns Study.

Author

Saarinen, Aino, Marttila, Saara, Mishra, Pashupati P., Lyytikäinen, Leo‐Pekka, Raitoharju, Emma, Mononen, Nina, Sormunen, Elina, Kähönen, Mika, Raitakari, Olli, Hietala, Jarmo, Keltikangas‐Järvinen, Liisa, and Lehtimäki, Terho

Subjects
MONOGENIC & polygenic inheritance (Genetics), REWARD (Psychology), EPIGENETICS, AGING, PREMATURE aging (Medicine)
Abstract

Schizophrenia is often regarded as a disorder of premature aging. We investigated (a) whether polygenic risk for schizophrenia (PRSsch) relates to pace of epigenetic aging and (b) whether personal dispositions toward active and emotionally close relationships protect against accelerated epigenetic aging in individuals with high PRSsch. The sample came from the population‐based Young Finns Study (n = 1348). Epigenetic aging was measured with DNA methylation aging algorithms such as AgeAccelHannum, EEAAHannum, IEAAHannum, IEAAHorvath, AgeAccelHorvath, AgeAccelPheno, AgeAccelGrim, and DunedinPACE. A PRSsch was calculated using summary statistics from the most comprehensive genome‐wide association study of schizophrenia to date. Social dispositions were assessed in terms of extraversion, sociability, reward dependence, cooperativeness, and attachment security. We found that PRSsch did not have a statistically significant effect on any studied indicator of epigenetic aging. Instead, PRSsch had a significant interaction with reward dependence (p = 0.001–0.004), cooperation (p = 0.009–0.020), extraversion (p = 0.019–0.041), sociability (p = 0.003–0.016), and attachment security (p = 0.007–0.014) in predicting AgeAccelHannum, EEAAHannum, or IEAAHannum. Specifically, participants with high PRSsch appeared to display accelerated epigenetic aging at higher (vs. lower) levels of extraversion, sociability, attachment security, reward dependence, and cooperativeness. A rather opposite pattern was evident for those with low PRSsch. No such interactions were evident when predicting the other indicators of epigenetic aging. In conclusion, against our hypothesis, frequent social interactions may relate to accelerated epigenetic aging in individuals at risk for psychosis. We speculate that this may be explained by social‐cognitive impairments (perceiving social situations as overwhelming or excessively arousing) or ending up in less supportive or deviant social groups. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Gene Set Based Integrated Methylome and Transcriptome Analysis Reveals Potential Molecular Mechanisms Linking Cigarette Smoking and Related Diseases

Author

Mishra, Pashupati P., primary, Mishra, Binisha H., additional, Raitoharju, Emma, additional, Mononen, Nina, additional, Viikari, Jorma, additional, Juonala, Markus, additional, Hutri-Kähönen, Nina, additional, Kähönen, Mika, additional, Raitakari, Olli T., additional, and Lehtimäki, Terho, additional

Published
2023
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16. Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes

Author

Mononen, Nina, Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Mishra, Pashupati P., Juonala, Markus, Waldenberger, Melanie, Klopp, Norman, Illig, Thomas, Leiviskä, Jaana, Loo, Britt-Marie, Laaksonen, Reijo, Oksala, Niku, Kähönen, Mika, Hutri-Kähönen, Nina, Raitakari, Olli, Lehtimäki, Terho, and Raitoharju, Emma

Published
2019
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19. Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues

Author

Marttila, Saara, primary, Tamminen, Hely, additional, Rajić, Sonja, additional, Mishra, Pashupati P, additional, Lehtimäki, Terho, additional, Raitakari, Olli, additional, Kähönen, Mika, additional, Kananen, Laura, additional, Jylhävä, Juulia, additional, Hägg, Sara, additional, Delerue, Thomas, additional, Peters, Annette, additional, Waldenberger, Melanie, additional, Kleber, Marcus E, additional, März, Winfried, additional, Luoto, Riitta, additional, Raitanen, Jani, additional, Sillanpää, Elina, additional, Laakkonen, Eija K, additional, Heikkinen, Aino, additional, Ollikainen, Miina, additional, and Raitoharju, Emma, additional

Published
2022
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22. 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

Published
2015
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24. Mitochondrial genome-wide analysis of nuclear DNA methylation quantitative trait loci

Author

Laaksonen, Jaakko, primary, Mishra, Pashupati P, additional, Seppälä, Ilkka, additional, Raitoharju, Emma, additional, Marttila, Saara, additional, Mononen, Nina, additional, Lyytikäinen, Leo-Pekka, additional, Kleber, Marcus E, additional, Delgado, Graciela E, additional, Lepistö, Maija, additional, Almusa, Henrikki, additional, Ellonen, Pekka, additional, Lorkowski, Stefan, additional, März, Winfried, additional, Hutri-Kähönen, Nina, additional, Raitakari, Olli, additional, Kähönen, Mika, additional, Salonen, Jukka T, additional, and Lehtimäki, Terho, additional

Published
2021
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25. Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia

Author

Auvinen, Juha, primary, Tapio, Joona, additional, Karhunen, Ville, additional, Kettunen, Johannes, additional, Serpi, Raisa, additional, Dimova, Elitsa Y., additional, Gill, Dipender, additional, Soininen, Pasi, additional, Tammelin, Tuija, additional, Mykkänen, Juha, additional, Puukka, Katri, additional, Kähönen, Mika, additional, Raitoharju, Emma, additional, Lehtimäki, Terho, additional, Ala-Korpela, Mika, additional, Raitakari, Olli T., additional, Keinänen-Kiukaanniemi, Sirkka, additional, Järvelin, Marjo-Riitta, additional, and Koivunen, Peppi, additional

Published
2021
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27. Additional file 1 of Reproductive history and blood cell DNA methylation later in life: the Young Finns Study

Author

Harville, Emily W., Mishra, Pashupati P., K��h��nen, Mika, Raitoharju, Emma, Marttila, Saara, Raitakari, Olli, and Lehtim��ki, Terho

Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, ComputingMilieux_COMPUTERSANDEDUCATION, Data_FILES, ComputerApplications_COMPUTERSINOTHERSYSTEMS
Abstract

Additional file 1. Supplementary tables and figures.

Published
2021
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28. Additional file 1 of Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs

Author

Marttila, Saara, Viiri, Leena E., Mishra, Pashupati P., Kühnel, Brigitte, Matias-Garcia, Pamela R., Lyytikäinen, Leo-Pekka, Ceder, Tiina, Mononen, Nina, Rathmann, Wolfgang, Winkelmann, Juliane, Peters, Annette, Kähönen, Mika, Hutri-Kähönen, Nina, Juonala, Markus, Aalto-Setälä, Katriina, Raitakari, Olli, Lehtimäki, Terho, Waldenberger, Melanie, and Raitoharju, Emma

Abstract

Additional file 1. Supplementary Figures S1-6, Supplementary Tables S1-3 and S11-13 and Supplementary materials and methods.

Published
2021
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29. Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis: The Young Finns Study

Author

Hamal Mishra Binisha, Mishra P Pashupati, Raitoharju Emma, Marttila Saara, Mononen Nina, Sievänen Harri, Viikari Jorma, Juonala Markus, Laaksonen Marika, Hutri-Kähönen Nina, Kähönen Mika, T. Raitakari Olli, and Lehtimäki Terho

Subjects
mental disorders, Osteoporosis, atherosclerosis, comorbidity, gene expression data, weighted co-expression network analysis, MANOVA, pathway analysis
Abstract

The research focuses on the co-morbidity study of atherosclerosis and osteoporosis.

Published
2020
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30. Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs

Author

Marttila, Saara, Viiri, Leena E., Mishra, Pashupati P., Kühnel, Brigitte, Matias-Garcia, Pamela R., Lyytikäinen, Leo-Pekka, Ceder, Tiina, Mononen, Nina, Rathmann, Wolfgang, Winkelmann, Juliane, Peters, Annette, Kähönen, Mika, Hutri-Kähönen, Nina, Juonala, Markus, Aalto-Setälä, Katriina, Raitakari, Olli, Lehtimäki, Terho, Waldenberger, Melanie, and Raitoharju, Emma

Subjects
ddc
Published
2020

32. The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease

Author

Kalaoja, Marita, primary, Corbin, Laura J., additional, Tan, Vanessa Y., additional, Ahola‐Olli, Ari V., additional, Havulinna, Aki S., additional, Santalahti, Kristiina, additional, Pitkänen, Niina, additional, Lehtimäki, Terho, additional, Lyytikäinen, Leo‐Pekka, additional, Raitoharju, Emma, additional, Seppälä, Ilkka, additional, Kähönen, Mika, additional, Ripatti, Samuli, additional, Palotie, Aarno, additional, Perola, Markus, additional, Viikari, Jorma S., additional, Jalkanen, Sirpa, additional, Maksimow, Mikael, additional, Salomaa, Veikko, additional, Salmi, Marko, additional, Raitakari, Olli T., additional, Kettunen, Johannes, additional, and Timpson, Nicholas J., additional

Published
2021
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33. The TAXINOMISIS Project: A multidisciplinary approach for the development of a new risk stratification model for patients with asymptomatic carotid artery stenosis

Author

all partners of the TAXINOMISIS Consortium, Timmerman, Nathalie, Galyfos, George, Sigala, Fragiska, Thanopoulou, Kalliopi, de Borst, Gert J, Davidovic, Lazar, Eckstein, Hans-Henning, Filipovic, Nenad, Grugni, Roberto, Kallmayer, Michael, de Kleijn, Dominique P V, Koncar, Igor, Mantzaris, Michalis D, Marchal, Elisabeth, Matsagkas, Miltiadis, Mutavdzic, Perica, Palombo, Domenico, Pasterkamp, Gerard, Potsika, Vassiliki T, Andreakos, Evangelos, Fotiadis, Dimitrios I, Lehtimäki, Terho, Mishra, Pashupati, Raitoharju, Emma, Mononen, Nina, Tampere University, Clinical Medicine, and Department of Clinical Chemistry

Subjects
Male, medicine.medical_treatment, Clinical Biochemistry, Method, risk stratification, 030204 cardiovascular system & hematology, carotid artery stenosis, Biochemistry, 0302 clinical medicine, Theoretical, Multidisciplinary approach, Models, Lab-On-A-Chip Devices, Clinical endpoint, Methods, Carotid Stenosis, 030212 general & internal medicine, Prospective Studies, pharmacogenetics, Hypolipidemic Agents, Endarterectomy, Carotid, Endovascular Procedures, General Medicine, Middle Aged, ddc, 3. Good health, Stroke, Disease Progression, Biomarker (medicine), biomarker, Female, Stents, medicine.medical_specialty, Endarterectomy, Revascularization, 3121 Internal medicine, Risk Assessment, 03 medical and health sciences, Clinical Decision Rules, medicine, Humans, Intensive care medicine, Aged, Carotid, business.industry, Anticoagulants, Vascular surgery, Models, Theoretical, Pharmacogenomic Testing, Clinical trial, Asymptomatic Diseases, Observational study, Biomarkers, Platelet Aggregation Inhibitors, 3111 Biomedicine, business, Pharmacogenetics
Abstract

INTRODUCTION: Asymptomatic carotid artery stenosis (ACAS) may cause future stroke and therefore patients with ACAS require best medical treatment. Patients at high risk for stroke may opt for additional revascularization (either surgery or stenting) but the future stroke risk should outweigh the risk for peri/post-operative stroke/death. Current risk stratification for patients with ACAS is largely based on outdated randomized-controlled trials that lack the integration of improved medical therapies and risk factor control. Furthermore, recent circulating and imaging biomarkers for stroke have never been included in a risk stratification model. The TAXINOMISIS Project aims to develop a new risk stratification model for cerebrovascular complications in patients with ACAS and this will be tested through a prospective observational multicentre clinical trial performed in six major European vascular surgery centres. METHODS AND ANALYSIS: The risk stratification model will compromise clinical, circulating, plaque and imaging biomarkers. The prospective multicentre observational study will include 300 patients with 50%-99% ACAS. The primary endpoint is the three-year incidence of cerebrovascular complications. Biomarkers will be retrieved from plasma samples, brain MRI, carotid MRA and duplex ultrasound. The TAXINOMISIS Project will serve as a platform for the development of new computer tools that assess plaque progression based on radiology images and a lab-on-chip with genetic variants that could predict medication response in individual patients. CONCLUSION: Results from the TAXINOMISIS study could potentially improve future risk stratification in patients with ACAS to assist personalized evidence-based treatment decision-making. publishedVersion

Published
2020

34. Epigenome-450K-wide methylation signatures of active cigarette smoking : The Young Finns Study

Author

Mishra, Pashupati P., Hänninen, Ismo, Raitoharju, Emma, Marttila, Saara, Mishra, Binisha H., Mononen, Nina, Kähönen, Mika, Hurme, Mikko, Raitakari, Olli, Törönen, Petri, Holm, Liisa, Lehtimaki, Terho, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, Tampere University, Institute of Biotechnology, Computational genomics, Genetics, Bioinformatics, and Organismal and Evolutionary Biology Research Programme

Subjects
Biolääketieteet - Biomedicine, CARDIOVASCULAR RISK, GLIOMA, 1182 Biochemistry, cell and molecular biology, DNA METHYLATION, ISLANDS, METAANALYSIS
Abstract

Smoking as a major risk factor for morbidity affects numerous regulatory systems of the human body including DNA methylation. Most of the previous studies with genome-wide methylation data are based on conventional association analysis and earliest threshold-based gene set analysis that lacks sensitivity to be able to reveal all the relevant effects of smoking. The aim of the present study was to investigate the impact of active smoking on DNA methylation at three biological levels: 5'-C-phosphate-G-3' (CpG) sites, genes and functionally related genes (gene sets). Gene set analysis was done with mGSZ, a modern threshold-free method previously developed by us that utilizes all the genes in the experiment and their differential methylation scores. Application of such method in DNA methylation study is novel. Epigenome-wide methylation levels were profiled from Young Finns Study (YFS) participants' whole blood from 2011 follow-up using Illumina Infinium Hu-manMethylation450 BeadChips. We identified three novel smoking related CpG sites and replicated 57 of the previously identified ones. We found that smoking is associated with hypomethylation in shore (genomic regions 0-2 kilobases from CpG island). We identified smoking related methylation changes in 13 gene sets with false discovery rate (FDR)

Published
2020

36. Epigenome-450K-wide methylation signatures of active cigarette smoking: The Young Finns Study

Author

Mishra, Pashupati P., primary, Hänninen, Ismo, additional, Raitoharju, Emma, additional, Marttila, Saara, additional, Mishra, Binisha H., additional, Mononen, Nina, additional, Kähönen, Mika, additional, Hurme, Mikko, additional, Raitakari, Olli, additional, Törönen, Petri, additional, Holm, Liisa, additional, and Lehtimäki, Terho, additional

Published
2020
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37. RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease

Author

Holvoet, Paul, primary, Klocke, Bernward, additional, Vanhaverbeke, Maarten, additional, Menten, Roxane, additional, Sinnaeve, Peter, additional, Raitoharju, Emma, additional, Lehtimäki, Terho, additional, Oksala, Niku, additional, Zinser, Christian, additional, Janssens, Stefan, additional, Sipido, Karin, additional, Lyytikainen, Leo-Pekka, additional, and Cagnin, Stefano, additional

Published
2019
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38. Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy

Author

Nath, Artika P., primary, Ritchie, Scott C., additional, Grinberg, Nastasiya F., additional, Tang, Howard Ho-Fung, additional, Huang, Qin Qin, additional, Teo, Shu Mei, additional, Ahola-Olli, Ari V., additional, Würtz, Peter, additional, Havulinna, Aki S., additional, Santalahti, Kristiina, additional, Pitkänen, Niina, additional, Lehtimäki, Terho, additional, Kähönen, Mika, additional, Lyytikäinen, Leo-Pekka, additional, Raitoharju, Emma, additional, Seppälä, Ilkka, additional, Sarin, Antti-Pekka, additional, Ripatti, Samuli, additional, Palotie, Aarno, additional, Perola, Markus, additional, Viikari, Jorma S., additional, Jalkanen, Sirpa, additional, Maksimow, Mikael, additional, Salmi, Marko, additional, Wallace, Chris, additional, Raitakari, Olli T., additional, Salomaa, Veikko, additional, Abraham, Gad, additional, Kettunen, Johannes, additional, and Inouye, Michael, additional

Published
2019
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39. Three genetic–environmental networks for human personality

Author

Zwir, Igor, Del-Val, Coral, Arnedo, Javier, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Seppälä, Ilkka, Raitoharju, Emma, Lehtimäki, Terho, et al, Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, and Tampere University

Subjects
Biolääketieteet - Biomedicine, Neurotieteet - Neurosciences
Published
2019

40. Uncovering the Complex Genetics of Human Character

Author

Zwir, Igor, Arnedo, Javier, Del-Val, Coral, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Lehtimäki, Terho, Raitoharju, Emma, Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, and Tampere University

Subjects
Genetiikka, kehitysbiologia, fysiologia - Genetics, developmental biology, physiology, Biolääketieteet - Biomedicine
Published
2018

41. Uncovering the complex genetics of human temperament

Author

Zwir, Igor, Arnedo, Javier, Del-Val, Coral, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Lehtimäki, Terho, Raitoharju, Emma, Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, and Tampere University

Subjects
Genetiikka, kehitysbiologia, fysiologia - Genetics, developmental biology, physiology, Neurologia ja psykiatria - Neurology and psychiatry
Published
2018

42. Genetic and environmental perturbations lead to regulatory decoherence

Author

Lea, Amanda, primary, Subramaniam, Meena, additional, Ko, Arthur, additional, Lehtimäki, Terho, additional, Raitoharju, Emma, additional, Kähönen, Mika, additional, Seppälä, Ilkka, additional, Mononen, Nina, additional, Raitakari, Olli T, additional, Ala-Korpela, Mika, additional, Pajukanta, Päivi, additional, Zaitlen, Noah, additional, and Ayroles, Julien F, additional

Published
2019
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43. Discovery of mitochondrial DNA variants associated with genome-wide blood cell gene expression: a population-based mtDNA sequencing study

Author

Laaksonen, Jaakko, primary, Seppälä, Ilkka, additional, Raitoharju, Emma, additional, Mononen, Nina, additional, Lyytikäinen, Leo-Pekka, additional, Waldenberger, Melanie, additional, Illig, Thomas, additional, Lepistö, Maija, additional, Almusa, Henrikki, additional, Ellonen, Pekka, additional, Hutri-Kähönen, Nina, additional, Juonala, Markus, additional, Kähönen, Mika, additional, Raitakari, Olli, additional, Salonen, Jukka T, additional, and Lehtimäki, Terho, additional

Published
2019
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44. Uncovering the complex genetics of human character

Author

Zwir, Igor, primary, Arnedo, Javier, additional, Del-Val, Coral, additional, Pulkki-Råback, Laura, additional, Konte, Bettina, additional, Yang, Sarah S., additional, Romero-Zaliz, Rocio, additional, Hintsanen, Mirka, additional, Cloninger, Kevin M., additional, Garcia, Danilo, additional, Svrakic, Dragan M., additional, Rozsa, Sandor, additional, Martinez, Maribel, additional, Lyytikäinen, Leo-Pekka, additional, Giegling, Ina, additional, Kähönen, Mika, additional, Hernandez-Cuervo, Helena, additional, Seppälä, Ilkka, additional, Raitoharju, Emma, additional, de Erausquin, Gabriel A., additional, Raitakari, Olli, additional, Rujescu, Dan, additional, Postolache, Teodor T., additional, Sung, Joohon, additional, Keltikangas-Järvinen, Liisa, additional, Lehtimäki, Terho, additional, and Cloninger, C. Robert, additional

Published
2018
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45. Uncovering the complex genetics of human temperament

Author

Zwir, Igor, primary, Arnedo, Javier, additional, Del-Val, Coral, additional, Pulkki-Råback, Laura, additional, Konte, Bettina, additional, Yang, Sarah S., additional, Romero-Zaliz, Rocio, additional, Hintsanen, Mirka, additional, Cloninger, Kevin M., additional, Garcia, Danilo, additional, Svrakic, Dragan M., additional, Rozsa, Sandor, additional, Martinez, Maribel, additional, Lyytikäinen, Leo-Pekka, additional, Giegling, Ina, additional, Kähönen, Mika, additional, Hernandez-Cuervo, Helena, additional, Seppälä, Ilkka, additional, Raitoharju, Emma, additional, de Erausquin, Gabriel A., additional, Raitakari, Olli, additional, Rujescu, Dan, additional, Postolache, Teodor T., additional, Sung, Joohon, additional, Keltikangas-Järvinen, Liisa, additional, Lehtimäki, Terho, additional, and Cloninger, C. Robert, additional

Published
2018
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47. Experimental and Human Evidence for Lipocalin‐2 (Neutrophil Gelatinase‐Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and Heart Failure

Author

Marques, Francine Z., primary, Prestes, Priscilla R., additional, Byars, Sean G., additional, Ritchie, Scott C., additional, Würtz, Peter, additional, Patel, Sheila K., additional, Booth, Scott A., additional, Rana, Indrajeetsinh, additional, Minoda, Yosuke, additional, Berzins, Stuart P., additional, Curl, Claire L., additional, Bell, James R., additional, Wai, Bryan, additional, Srivastava, Piyush M., additional, Kangas, Antti J., additional, Soininen, Pasi, additional, Ruohonen, Saku, additional, Kähönen, Mika, additional, Lehtimäki, Terho, additional, Raitoharju, Emma, additional, Havulinna, Aki, additional, Perola, Markus, additional, Raitakari, Olli, additional, Salomaa, Veikko, additional, Ala‐Korpela, Mika, additional, Kettunen, Johannes, additional, McGlynn, Maree, additional, Kelly, Jason, additional, Wlodek, Mary E., additional, Lewandowski, Paul A., additional, Delbridge, Lea M., additional, Burrell, Louise M., additional, Inouye, Michael, additional, Harrap, Stephen B., additional, and Charchar, Fadi J., additional

Published
2017
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48. Differentially expressed genes and canonical pathways in the ascending thoracic aortic aneurysm – The Tampere Vascular Study

Author

Sulkava, Miska, primary, Raitoharju, Emma, additional, Mennander, Ari, additional, Levula, Mari, additional, Seppälä, Ilkka, additional, Lyytikäinen, Leo-Pekka, additional, Järvinen, Otso, additional, Illig, Thomas, additional, Klopp, Norman, additional, Mononen, Nina, additional, Laaksonen, Reijo, additional, Kähönen, Mika, additional, Oksala, Niku, additional, and Lehtimäki, Terho, additional

Published
2017
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49. An interaction map of circulating metabolites, immune gene networks, and their genetic regulation

Author

Nath, Artika P., primary, Ritchie, Scott C., additional, Byars, Sean G., additional, Fearnley, Liam G., additional, Havulinna, Aki S., additional, Joensuu, Anni, additional, Kangas, Antti J., additional, Soininen, Pasi, additional, Wennerström, Annika, additional, Milani, Lili, additional, Metspalu, Andres, additional, Männistö, Satu, additional, Würtz, Peter, additional, Kettunen, Johannes, additional, Raitoharju, Emma, additional, Kähönen, Mika, additional, Juonala, Markus, additional, Palotie, Aarno, additional, Ala-Korpela, Mika, additional, Ripatti, Samuli, additional, Lehtimäki, Terho, additional, Abraham, Gad, additional, Raitakari, Olli, additional, Salomaa, Veikko, additional, Perola, Markus, additional, and Inouye, Michael, additional

Published
2017
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50. Melanocortin 1 Receptor Signaling Regulates Cholesterol Transport in Macrophages

Author

Rinne, Petteri, primary, Rami, Martina, additional, Nuutinen, Salla, additional, Santovito, Donato, additional, van der Vorst, Emiel P.C., additional, Guillamat-Prats, Raquel, additional, Lyytikäinen, Leo-Pekka, additional, Raitoharju, Emma, additional, Oksala, Niku, additional, Ring, Larisa, additional, Cai, Minying, additional, Hruby, Victor J., additional, Lehtimäki, Terho, additional, Weber, Christian, additional, and Steffens, Sabine, additional

Published
2017
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