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2. A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk

Author

Ferrell, Marc, Wang, Zeneng, Anderson, James T., Li, Xinmin S., Witkowski, Marco, DiDonato, Joseph A., Hilser, James R., Hartiala, Jaana A., Haghikia, Arash, Cajka, Tomas, Fiehn, Oliver, Sangwan, Naseer, Demuth, Ilja, König, Maximilian, Steinhagen-Thiessen, Elisabeth, Landmesser, Ulf, Tang, W. H. Wilson, Allayee, Hooman, and Hazen, Stanley L.

Published
2024
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3. The artificial sweetener erythritol and cardiovascular event risk.

Author

Witkowski, Marco, Nemet, Ina, Alamri, Hassan, Wilcox, Jennifer, Gupta, Nilaksh, Nimer, Nisreen, Haghikia, Arash, Li, Xinmin, Wu, Yuping, Saha, Prasenjit, Demuth, Ilja, König, Maximilian, Steinhagen-Thiessen, Elisabeth, Cajka, Tomas, Landmesser, Ulf, Tang, W, Hazen, Stanley, and Fiehn, Oliver

Subjects
Humans, Sweetening Agents, Prospective Studies, Erythritol, Myocardial Infarction, Heart
Abstract

Artificial sweeteners are widely used sugar substitutes, but little is known about their long-term effects on cardiometabolic disease risks. Here we examined the commonly used sugar substitute erythritol and atherothrombotic disease risk. In initial untargeted metabolomics studies in patients undergoing cardiac risk assessment (n = 1,157; discovery cohort, NCT00590200 ), circulating levels of multiple polyol sweeteners, especially erythritol, were associated with incident (3 year) risk for major adverse cardiovascular events (MACE; includes death or nonfatal myocardial infarction or stroke). Subsequent targeted metabolomics analyses in independent US (n = 2,149, NCT00590200 ) and European (n = 833, DRKS00020915 ) validation cohorts of stable patients undergoing elective cardiac evaluation confirmed this association (fourth versus first quartile adjusted hazard ratio (95% confidence interval), 1.80 (1.18-2.77) and 2.21 (1.20-4.07), respectively). At physiological levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo. Finally, in a prospective pilot intervention study ( NCT04731363 ), erythritol ingestion in healthy volunteers (n = 8) induced marked and sustained (>2 d) increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies. Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of erythritol are warranted.

Published
2023

4. No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy

Author

Fjell, Anders M., Sørensen, Øystein, Wang, Yunpeng, Amlien, Inge K., Baaré, William F. C., Bartrés-Faz, David, Bertram, Lars, Boraxbekk, Carl-Johan, Brandmaier, Andreas M., Demuth, Ilja, Drevon, Christian A., Ebmeier, Klaus P., Ghisletta, Paolo, Kievit, Rogier, Kühn, Simone, Madsen, Kathrine Skak, Mowinckel, Athanasia M., Nyberg, Lars, Sexton, Claire E., Solé-Padullés, Cristina, Vidal-Piñeiro, Didac, Wagner, Gerd, Watne, Leiv Otto, and Walhovd, Kristine B.

Published
2023
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5. Publisher Correction: A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk

Author

Ferrell, Marc, Wang, Zeneng, Anderson, James T., Li, Xinmin S., Witkowski, Marco, DiDonato, Joseph A., Hilser, James R., Hartiala, Jaana A., Haghikia, Arash, Cajka, Tomas, Fiehn, Oliver, Sangwan, Naseer, Demuth, Ilja, König, Maximilian, Steinhagen-Thiessen, Elisabeth, Landmesser, Ulf, Tang, W. H. Wilson, Allayee, Hooman, and Hazen, Stanley L.

Published
2024
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14. Gut microbial metabolite imidazole propionate impairs endothelial cell function and promotes the development of atherosclerosis

Author

Nageswaran, Vanasa, primary, Carreras, Alba, additional, Reinshagen, Leander, additional, Beck, Katharina R., additional, Steinfeldt, Jakob, additional, Ståhlman, Marcus, additional, Ramezani Rad, Pegah, additional, Lim, Joseph, additional, Strässler, Elisabeth Tamara, additional, Verhaar, Barbara J.H., additional, Döring, Yvonne, additional, Weber, Christian, additional, König, Maximilian, additional, Steinhagen-thiessen, Elisabeth, additional, Demuth, Ilja, additional, Kränkel, Nicolle, additional, Leistner, David Manuel, additional, Nieuwdorp, Max, additional, Knaus, Petra, additional, Ferrell, Marc, additional, Potente, Michael, additional, Hazen, Stanley L., additional, Landmesser, Ulf, additional, Bäckhed, Fredrik, additional, and Haghikia, Arash, additional

Published
2024
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16. Disentangling the genetics of lean mass.

Author

Karasik, David, Zillikens, M, Hsu, Yi-Hsiang, Aghdassi, Ali, Akesson, Kristina, Amin, Najaf, Barroso, Inês, Bennett, David, Bertram, Lars, Bochud, Murielle, Borecki, Ingrid, Broer, Linda, Buchman, Aron, Byberg, Liisa, Campbell, Harry, Campos-Obando, Natalia, Cauley, Jane, Cawthon, Peggy, Chambers, John, Chen, Zhao, Cho, Nam, Choi, Hyung, Chou, Wen-Chi, Cummings, Steven, de Groot, Lisette, De Jager, Phillip, Demuth, Ilja, Diatchenko, Luda, Econs, Michael, Eiriksdottir, Gudny, Enneman, Anke, Eriksson, Joel, Eriksson, Johan, Estrada, Karol, Evans, Daniel, Feitosa, Mary, Fu, Mao, Gieger, Christian, Grallert, Harald, Gudnason, Vilmundur, Lenore, Launer, Hayward, Caroline, Hofman, Albert, Homuth, Georg, Huffman, Kim, Husted, Lise, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Johnson, Toby, Biffar, Reiner, Jordan, Joanne, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas, Klopp, Norman, Kloth, Jacqueline, Koller, Daniel, Kooner, Jaspal, Kraus, William, Kritchevsky, Stephen, Kutalik, Zoltán, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Langdahl, Bente, Lerch, Markus, Lewis, Joshua, Lill, Christina, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Livshits, Gregory, Ljunggren, Östen, Loos, Ruth, Lorentzon, Mattias, Luan, Jianan, Luben, Robert, Malkin, Ida, McGuigan, Fiona, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Michaëlsson, Karl, Mitchell, Braxton, Morris, Andrew, Mosekilde, Leif, Nethander, Maria, Newman, Anne, OConnell, Jeffery, Oostra, Ben, Orwoll, Eric, Palotie, Aarno, Peacock, Munro, Perola, Markus, and Peters, Annette

Subjects
ADAMTS Proteins, Absorptiometry, Photon, Adipose Tissue, Adolescent, Adult, Aged, Aged, 80 and over, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Composition, Body Fluid Compartments, Electric Impedance, Extracellular Matrix Proteins, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Muscle, Skeletal, Phenotype, Polymorphism, Single Nucleotide, RNA-Binding Proteins, Receptor, Melanocortin, Type 4, Versicans, White People, Young Adult
Abstract

BACKGROUND: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. OBJECTIVES: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. METHODS: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). RESULTS: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as sumo wrestler loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed body builder loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in body builder loci were associated with metabolic protection. CONCLUSIONS: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

Published
2019

21. Berlin Aging Study II (BASE-II)

Author

Demuth, Ilja, Bertram, Lars, Drewelies, Johanna, Düzel, Sandra, Lill, Christina M., Lindenberger, Ulman, Pawelec, Graham, Spira, Dominik, Wagner, Gert G., Gerstorf, Denis, Dupre, Matthew E., Section editor, Gu, Danan, editor, and Dupre, Matthew E., editor

Published
2021
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22. Lipoprotein(a) and Lung Function Are Associated in Older Adults: Longitudinal and Cross-Sectional Analyses.

Author

Song, Chae Kyung, Ohlei, Olena, Keller, Theresa, Regitz-Zagrosek, Vera, Toepfer, Sarah, Steinhagen-Thiessen, Elisabeth, Bertram, Lars, Buchmann, Nikolaus, and Demuth, Ilja

Subjects
FORCED expiratory volume, VITAL capacity (Respiration), GENOME-wide association studies, OLDER people, GENETICS
Abstract

While numerous studies have confirmed a causal association between lipoprotein(a) [Lp(a)] and cardiovascular diseases, only a few studies have assessed the relationship between Lp(a) and pulmonary health, with inconsistent findings regarding this topic. This study's aim was to examine whether levels of serum Lp(a) are associated with lung function in a dataset of relatively healthy older adults. We used longitudinal data collected at two time points 7.4 ± 1.5 years apart from 679 participants (52% women, 68 [65–71] years old) from the Berlin Aging Study II (BASE-II). Multiple linear regression models adjusting for covariates were applied to examine the association between Lp(a) and lung function. The forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) were higher in both men and women with higher Lp(a) levels. However, since this association between lung function parameters and Lp(a) was not supported by Mendelian randomization analyses using recent genome-wide association study data, these relationships should be investigated in future work, as the observed differences are, in part, considerable and potentially clinically relevant. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Author

Zillikens, M Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M, Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L, Kutalik, Zoltán, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Hua Zhao, Jing, Zhang, Weihua, Aghdassi, Ali, Åkesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Inês, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos Obanda, Natalia, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Jin Choi, Hyung, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie AM, Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W, Erdos, Mike, Eriksson, Johan G, Eriksson, Joel, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L, Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L, Hayward, Caroline, Hofman, Albert, Hoffman, Eric P, Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J, Hubbard, Alan, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline SL, Koistinen, Heikki A, Kraus, William E, Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Launer, Lenore J, Lee, Jong-Young, Lerch, Markus M, Lewis, Joshua R, Lind, Lars, Lindgren, Cecilia, and Liu, Yongmei

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics
Abstract

A correction to this article has been published and is linked from the HTML version of this article.

Published
2017

25. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Author

Zillikens, M Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M, Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L, Kutalik, Zoltán, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Hua Zhao, Jing, Zhang, Weihua, Aghdassi, Ali, Åkesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Inês, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos Obanda, Natalia, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Jin Choi, Hyung, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie AM, Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W, Erdos, Mike, Eriksson, Johan G, Eriksson, Joel, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L, Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L, Hayward, Caroline, Hofman, Albert, Hoffman, Eric P, Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J, Hubbard, Alan, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline SL, Koistinen, Heikki A, Kraus, William E, Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Launer, Lenore J, Lee, Jong-Young, Lerch, Markus M, Lewis, Joshua R, Lind, Lars, Lindgren, Cecilia, and Liu, Yongmei

Subjects
Humans, Thinness, 17-Hydroxysteroid Dehydrogenases, Aldehyde Oxidoreductases, Extracellular Matrix Proteins, Body Composition, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Regulatory Elements, Transcriptional, Versicans, Genome-Wide Association Study, Insulin Receptor Substrate Proteins, ADAMTS Proteins, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Human Genome, Genetics, 1.1 Normal biological development and functioning
Abstract

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p

Published
2017

27. A Novel Variant in the WRN Gene Detected in a Case of Early-Onset Severe Insulin Resistance Displaying Some but Not All Hallmarks of Progeroid Werner Syndrome.

Author

Spira, Dominik, Herbst, Susanne, Schwartzmann, Sarina, Dutrannoy, Véronique, Steinhagen-Thiessen, Elisabeth, Demuth, Ilja, Maurer, Lukas, Mai, Knut, Spranger, Joachim, Mundlos, Stefan, and Bobbert, Thomas

Subjects
INSULIN resistance, WERNER'S syndrome, GENETIC variation, GENETIC testing, DIFFERENTIAL diagnosis
Abstract

OBJECTIVE: Determining the cause of severe insulin resistance and early-onset diabetes in the case of a young woman in which a wide range of differential diagnoses did not apply. RESEARCH DESIGN AND METHODS: Diagnostic workup including medical history, physical examination, specialist consultations, imaging methods, laboratory assessment, and genetic testing carried out by next-generation panel sequencing. RESULTS: After ruling out several differential diagnoses, genetic testing revealed a previously unknown homozygous variant within the canonical splice site of intron 4 in the WRN gene classified as pathogenic. Thus, although not all cardinal clinical criteria according to existing guidelines had been met, the phenotype of our patient was attributed to Werner syndrome (WS), an autosomal-recessive inherited progeroid syndrome. CONCLUSIONS: WS, although rare, must be considered as a differential diagnosis in cases of severe insulin resistance. Moreover, recognized clinical criteria of WS may not lead to diagnosis in all cases. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Genome-wide association study identifies 74 loci associated with educational attainment

Author

Okbay, Aysu, Beauchamp, Jonathan P, Fontana, Mark Alan, Lee, James J, Pers, Tune H, Rietveld, Cornelius A, Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Meddens, S Fleur W, Oskarsson, Sven, Pickrell, Joseph K, Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Abdellaoui, Abdel, Ahluwalia, Tarunveer S, Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H, Pina Concas, Maria, Derringer, Jaime, Furlotte, Nicholas A, Galesloot, Tessel E, Girotto, Giorgia, Gupta, Richa, Hall, Leanne M, Harris, Sarah E, Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E, Kaasik, Kadri, Kalafati, Ioanna P, Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J van der, deLeeuw, Christiaan, Lind, Penelope A, Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B, van der Most, Peter J, Oldmeadow, Christopher, Payton, Antony, Pervjakova, Natalia, Peyrot, Wouter J, Qian, Yong, Raitakari, Olli, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E, Shi, Jianxin, Smith, Albert V, Poot, Raymond A, St Pourcain, Beate, Teumer, Alexander, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Westra, Harm-Jan, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z, Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E, Biino, Ginevra, Bønnelykke, Klaus, Boyle, Patricia A, Campbell, Harry, Cappuccio, Francesco P, Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eibich, Peter, Eisele, Lewin, Eklund, Niina, Evans, David M, Faul, Jessica D, Feitosa, Mary F, Forstner, Andreas J, Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V, Harris, Tamara B, Heath, Andrew C, Hocking, Lynne J, Holliday, Elizabeth G, Homuth, Georg, and Horan, Michael A

Subjects
Biological Sciences, Genetics, Epidemiology, Health Sciences, Statistics, Mathematical Sciences, Human Genome, Clinical Research, Alzheimer Disease, Bipolar Disorder, Brain, Cognition, Computational Biology, Educational Status, Fetus, Gene Expression Regulation, Gene-Environment Interaction, Genome-Wide Association Study, Humans, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Schizophrenia, United Kingdom, LifeLines Cohort Study, General Science & Technology
Abstract

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

Published
2016

29. Genome-wide QTL mapping across three tissues highlights several Alzheimer's and Parkinson's disease loci potentially acting via DNA methylation

Author

Ohlei, Olena, primary, Sommerer, Yasmine, additional, Dobricic, Valerija, additional, Homann, Jan, additional, Deecke, Laura, additional, Schilling, Marcel, additional, Bartres-Faz, David, additional, Cattaneo, Gabriele, additional, Duezel, Sandra, additional, Fjell, Anders M, additional, Lindenberger, Ulman, additional, Pascal-Leone, Alvaro, additional, Sabet, Sanaz S, additional, Sole-Padulles, Cristina, additional, Tormos, Josep M, additional, Vetter, Valentin M, additional, Walhovd, Kristine B, additional, Wesse, Tanja, additional, Wittig, Michael, additional, Franke, Andre, additional, Demuth, Ilja, additional, Lill, Christina M, additional, and Bertram, Lars, additional

Published
2023
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30. Prognostic Value of Gut Microbe‐Generated Metabolite Phenylacetylglutamine in Patients with Heart Failure

Author

Tang, W. H. Wilson, primary, Nemet, Ina, additional, Li, Xinmin S., additional, Wu, Yuping, additional, Haghikia, Arash, additional, Witkowski, Marco, additional, Koeth, Robert A., additional, Demuth, Ilja, additional, König, Maximilian, additional, Steinhagen‐Thiessen, Elisabeth, additional, Bäckhed, Fredrik, additional, Fischbach, Michael A., additional, Deb, Arjun, additional, Landmesser, Ulf, additional, and Hazen, Stanley L., additional

Published
2023
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34. Variants in the TERT gene increase the occurrence of solar lentigines by modifying telomerase expression exclusively in the skin

Author

Deecke, Laura, primary, Ohlei, Olena, additional, Homann, Jan, additional, Stagge, Jessica, additional, Dobricic, Valerija, additional, Steinhagen-Thiessen, Elisabeth, additional, Berger, Klaus, additional, Demuth, Ilja, additional, Hagelstein, Victoria, additional, Bertram, Lars, additional, and Lill, Christina M., additional

Published
2023
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35. SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

Author

Braun, Julian, Loyal, Lucie, Frentsch, Marco, Wendisch, Daniel, Georg, Philipp, Kurth, Florian, Hippenstiel, Stefan, Dingeldey, Manuela, Kruse, Beate, Fauchere, Florent, Baysal, Emre, Mangold, Maike, Henze, Larissa, Lauster, Roland, Mall, Marcus A., Beyer, Kirsten, Röhmel, Jobst, Voigt, Sebastian, Schmitz, Jürgen, Miltenyi, Stefan, Demuth, Ilja, Müller, Marcel A., Hocke, Andreas, Witzenrath, Martin, Suttorp, Norbert, Kern, Florian, Reimer, Ulf, Wenschuh, Holger, Drosten, Christian, Corman, Victor M., Giesecke-Thiel, Claudia, Sander, Leif Erik, and Thiel, Andreas

Published
2020
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36. Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women

Author

Jones, Garan, Trajanoska, Katerina, Santanasto, Adam J., Stringa, Najada, Kuo, Chia-Ling, Atkins, Janice L., Lewis, Joshua R., Duong, ThuyVy, Hong, Shengjun, Biggs, Mary L., Luan, Jian’an, Sarnowski, Chloe, Lunetta, Kathryn L., Tanaka, Toshiko, Wojczynski, Mary K., Cvejkus, Ryan, Nethander, Maria, Ghasemi, Sahar, Yang, Jingyun, Zillikens, M. Carola, Walter, Stefan, Sicinski, Kamil, Kague, Erika, Ackert-Bicknell, Cheryl L., Arking, Dan E., Windham, B. Gwen, Boerwinkle, Eric, Grove, Megan L., Graff, Misa, Spira, Dominik, Demuth, Ilja, van der Velde, Nathalie, de Groot, Lisette C. P. G. M., Psaty, Bruce M., Odden, Michelle C., Fohner, Alison E., Langenberg, Claudia, Wareham, Nicholas J., Bandinelli, Stefania, van Schoor, Natasja M., Huisman, Martijn, Tan, Qihua, Zmuda, Joseph, Mellström, Dan, Karlsson, Magnus, Bennett, David A., Buchman, Aron S., De Jager, Philip L., Uitterlinden, Andre G., Völker, Uwe, Kocher, Thomas, Teumer, Alexander, Rodriguéz-Mañas, Leocadio, García, Francisco J., Carnicero, José A., Herd, Pamela, Bertram, Lars, Ohlsson, Claes, Murabito, Joanne M., Melzer, David, Kuchel, George A., Ferrucci, Luigi, Karasik, David, Rivadeneira, Fernando, Kiel, Douglas P., and Pilling, Luke C.

Published
2021
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39. Directional dominance on stature and cognition in diverse human populations

Author

Joshi, Peter K, Esko, Tonu, Mattsson, Hannele, Eklund, Niina, Gandin, Ilaria, Nutile, Teresa, Jackson, Anne U, Schurmann, Claudia, Smith, Albert V, Zhang, Weihua, Okada, Yukinori, Stančáková, Alena, Faul, Jessica D, Zhao, Wei, Bartz, Traci M, Concas, Maria Pina, Franceschini, Nora, Enroth, Stefan, Vitart, Veronique, Trompet, Stella, Guo, Xiuqing, Chasman, Daniel I, O'Connel, Jeffrey R, Corre, Tanguy, Nongmaithem, Suraj S, Chen, Yuning, Mangino, Massimo, Ruggiero, Daniela, Traglia, Michela, Farmaki, Aliki-Eleni, Kacprowski, Tim, Bjonnes, Andrew, van der Spek, Ashley, Wu, Ying, Giri, Anil K, Yanek, Lisa R, Wang, Lihua, Hofer, Edith, Rietveld, Cornelius A, McLeod, Olga, Cornelis, Marilyn C, Pattaro, Cristian, Verweij, Niek, Baumbach, Clemens, Abdellaoui, Abdel, Warren, Helen R, Vuckovic, Dragana, Mei, Hao, Bouchard, Claude, Perry, John RB, Cappellani, Stefania, Mirza, Saira S, Benton, Miles C, Broeckel, Ulrich, Medland, Sarah E, Lind, Penelope A, Malerba, Giovanni, Drong, Alexander, Yengo, Loic, Bielak, Lawrence F, Zhi, Degui, van der Most, Peter J, Shriner, Daniel, Mägi, Reedik, Hemani, Gibran, Karaderi, Tugce, Wang, Zhaoming, Liu, Tian, Demuth, Ilja, Zhao, Jing Hua, Meng, Weihua, Lataniotis, Lazaros, van der Laan, Sander W, Bradfield, Jonathan P, Wood, Andrew R, Bonnefond, Amelie, Ahluwalia, Tarunveer S, Hall, Leanne M, Salvi, Erika, Yazar, Seyhan, Carstensen, Lisbeth, de Haan, Hugoline G, Abney, Mark, Afzal, Uzma, Allison, Matthew A, Amin, Najaf, Asselbergs, Folkert W, Bakker, Stephan JL, Barr, R Graham, Baumeister, Sebastian E, Benjamin, Daniel J, Bergmann, Sven, Boerwinkle, Eric, Bottinger, Erwin P, Campbell, Archie, Chakravarti, Aravinda, Chan, Yingleong, Chanock, Stephen J, Chen, Constance, and Chen, Y-D Ida

Subjects
Biological Sciences, Genetics, Clinical Research, Human Genome, Biological Evolution, Blood Pressure, Body Height, Cholesterol, LDL, Cognition, Cohort Studies, Educational Status, Female, Forced Expiratory Volume, Genome, Human, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype, General Science & Technology
Abstract

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Published
2015

43. Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection

Author

Motreff, Pascal, Belle, Loïc, Dupouy, Patrick, Barnay, Pierre, Meneveau, Nicolas, Gilard, Martine, Rioufol, Gilles, Range, Grégoire, Brunel, Philippe, Delarche, Nicolas, Filippi, Emmanuelle, Le Bivic, Louis, Harbaoui, Brahim, Benamer, Hakim, Cayla, Guillaume, Varenne, Olivier, Manzo-Silberman, Stephane Peggy, Silvain, Johanne, Spaulding, Christian, Caussin, Christophe, Gerbaud, Edouard, Valy, Yann, Koning, René, Lhermusier, Thibault, Champin, Stanislas, Salengro, Emmanuel, Fluttaz, Arnaud, Zabalawi, Amer, Cottin, Yves, Teiger, Emmanuel, Saint-Etienne, Christophe, Ducrocq, Grégory, Marliere, Stéphanie, Boiffard, Emmanuel, Aubry, Pierre, Georges, Jean Louis, Bresson, Didier, De Poli, Fabien, Karrillon, Gaëtan, Roule, Vincent, Bali, Laurent, Valla, Mathieu, Gerbay, Antoine, Houpe, David, Dubreuil, Olivier, Monnier, Arsène, Mayaud, Norbert, Manchuelle, Aurélie, Commeau, Philippe, Bedossa, Marc, Nikpay, Majid, Goel, Anuj, Won, Hong-Hee, Hall, Leanne M., Willenborg, Christina, Kanoni, Stavroula, Saleheen, Danish, Kyriakou, Theodosios, Nelson, Christopher P., Hopewell, Jemma C., Webb, Thomas R., Zeng, Lingyao, Dehghan, Abbas, Alver, Maris, Armasu, Sebastian M., Auro, Kirsi, Bjonnes, Andrew, Chasman, Daniel I., Chen, Shufeng, Ford, Ian, Franceschini, Nora, Gieger, Christian, Grace, Christopher, Gustafsson, Stefan, Huang, Jie, Hwang, Shih-Jen, Kim, Yun Kyoung, Kleber, Marcus E., Lau, King Wai, Lu, Xiangfeng, Lu, Yingchang, Lyytikäinen, Leo P., Mihailov, Evelin, Morrison, Alanna, Pervjakova, Natalia, Qu, Liming, Rose, Lynda M., Salfati, Elias, Saxena, Richa, Scholz, Markus, Smith, Albert V., Tikkanen, Emmi, Uitterlinden, Andre, Yang, Xueli, Zhang, Weihua, Zhao, Wei, de Andrade, Mariza, de Vries, Paul S., van Zuydam, Natalie R., Anand, Sonia S., Bertram, Lars, Beutner, Frank, Dedoussis, George, Frossard, Philippe, Gauguier, Dominique, Goodall, Alison H., Gottesman, Omri, Haber, Marc, Han, Bok-Ghee, Huang, Jianfeng, Jalilzadeh, Shapour, Kessler, Thorsten, König, Inke R., Lannfelt, Lars, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M., Lokki, Maisa, Magnusson, Patrik K., Mallick, Nadeem H., Mehra, Narinder, Meitinger, Thomas, Memon, Fazal-ur-Rehman, Morris, Andrew P., Nieminen, Markku S., Pedersen, Nancy L., Peters, Annette, Rallidis, Loukianos S., Rasheed, Asif, Samuel, Maria, Shah, Svati H., Sinisalo, Juha, Stirrups, Kathleen E., Trompet, Stella, Wang, Laiyuan, Zaman, Khan S., Ardissino, Diego, Boerwinkle, Eric, Borecki, Ingrid B., Bottinger, Erwin P., Buring, Julie E., Chambers, John C., Collins, Rory, Cupples, L Adrienne, Danesh, John, Demuth, Ilja, Elosua, Roberto, Epstein, Stephen E., Esko, Tõnu, Feitosa, Mary F., Franco, Oscar H., Franzosi, Maria Grazia, Granger, Christopher B., Gu, Dongfeng, Gudnason, Vilmundur, Hall, Alistair S., Hamsten, Anders, Harris, Tamara B., Hazen, Stanley L., Hengstenberg, Christian, Hofman, Albert, Ingelsson, Erik, Iribarren, Carlos, Jukema, J Wouter, Karhunen, Pekka J., Kim, Bong-Jo, Kooner, Jaspal S., Kullo, Iftikhar J., Lehtimäki, Terho, Loos, Ruth J., Melander, Olle, Metspalu, Andres, März, Winfried, Palmer, Colin N., Perola, Markus, Quertermous, Thomas, Rader, Daniel J., Ridker, Paul M., Ripatti, Samuli, Roberts, Robert, Salomaa, Veikko, Sanghera, Dharambir K., Schwartz, Stephen M., Seedorf, Udo, Stewart, Alexandre F., Stott, David J., Thiery, Joachim, Zalloua, Pierre A., O'Donnell, Christopher J., Reilly, Muredach P., Assimes, Themistocles L., Thompson, John R., Erdmann, Jeanette, Clarke, Robert, Watkins, Hugh, Kathiresan, Sekar, McPherson, Ruth, Deloukas, Panos, Schunkert, Heribert, Samani, Nilesh J., Farrall, Martin, Adlam, David, Olson, Timothy M., Combaret, Nicolas, Kovacic, Jason C., Iismaa, Siiri E., Al-Hussaini, Abtehale, O'Byrne, Megan M., Bouajila, Sara, Georges, Adrien, Mishra, Ketan, Braund, Peter S., d’Escamard, Valentina, Huang, Siying, Margaritis, Marios, Kadian-Dodov, Daniella, Welch, Catherine A., Mazurkiewicz, Stephani, Jeunemaitre, Xavier, Wong, Claire Mei Yi, Giannoulatou, Eleni, Sweeting, Michael, Muller, David, Wood, Alice, McGrath-Cadell, Lucy, Fatkin, Diane, Dunwoodie, Sally L., Harvey, Richard, Holloway, Cameron, Empana, Jean-Philippe, Jouven, Xavier, Olin, Jeffrey W., Gulati, Rajiv, Tweet, Marysia S., Hayes, Sharonne N., Graham, Robert M., and Bouatia-Naji, Nabila

Published
2019
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44. Prognostic value of gut microbe‐generated metabolite phenylacetylglutamine in patients with heart failure.

Author

Tang, W.H. Wilson, Nemet, Ina, Li, Xinmin S., Wu, Yuping, Haghikia, Arash, Witkowski, Marco, Koeth, Robert A., Demuth, Ilja, König, Maximilian, Steinhagen‐Thiessen, Elisabeth, Bäckhed, Fredrik, Fischbach, Michael A., Deb, Arjun, Landmesser, Ulf, and Hazen, Stanley L.

Subjects
PROGNOSIS, HEART failure patients, LIQUID chromatography-mass spectrometry, VENTRICULAR ejection fraction, GLOMERULAR filtration rate
Abstract

Aim: Phenylacetylglutamine (PAGln) is a phenylalanine‐derived metabolite produced by gut microbiota with mechanistic links to heart failure (HF)‐relevant phenotypes. We sought to investigate the prognostic value of PAGln in patients with stable HF. Methods and results: Fasting plasma PAGln levels were measured by stable‐isotope‐dilution liquid chromatography–tandem mass spectrometry (LC‐MS/MS) in patients with stable HF from two large cohorts. All‐cause mortality was assessed at 5‐year follow‐up in the Cleveland cohort, and HF, hospitalization, or mortality were assessed at 3‐year follow‐up in the Berlin cohort. Within the Cleveland cohort, median PAGln levels were 4.2 (interquartile range [IQR] 2.4–6.9) μM. Highest quartile of PAGln was associated with 3.09‐fold increased mortality risk compared to lowest quartile. Following adjustments for traditional risk factors, as well as race, estimated glomerular filtration rate, amino‐terminal pro‐B‐type natriuretic peptide, high‐sensitivity C‐reactive protein, left ventricular ejection fraction, ischaemic aetiology, and HF drug treatment, elevated PAGln levels remained predictive of 5‐year mortality in quartile comparisons (adjusted hazard ratio [HR] [95% confidence interval, CI] for Q4 vs Q1: 1.64 [1.07–2.53]). In the Berlin cohort, a similar distribution of PAGln levels was observed (median 3.2 [IQR 2.0–4.8] μM), and PAGln levels were associated with a 1.92‐fold increase in 3‐year HF hospitalization or all‐cause mortality risk (adjusted HR [95% CI] for Q4 vs Q1: 1.92 [1.02‐3.61]). Prognostic value of PAGln appears to be independent of trimethylamine N‐oxide levels. Conclusion: High levels of PAGln are associated with adverse outcomes independent of traditional cardiac risk factors and cardio‐renal risk markers. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Sex differences in the age-related decrease of spontaneous baroreflex function in healthy individuals.

Author

Schumann, Andy, Gupta, Yubraj, Gerstorf, Denis, Demuth, Ilja, and Bär, Karl-Jürgen

Subjects
BAROREFLEXES, PHYSIOLOGY, MIDDLE-aged women, AGE groups, BLOOD pressure
Abstract

The baroreflex is a powerful physiological mechanism for rapidly adjusting heart rate in response to changes in blood pressure. Spontaneous baroreflex sensitivity (BRS) has been shown to decrease with age. However, studies of sex differences in these age-related changes are rare. Here we investigated several markers of spontaneous baroreflex function in a large sample of healthy individuals. Cardiovascular signals were recorded in the supine position under carefully controlled resting conditions. After quality control, n = 980 subjects were divided into five age groups [age < 30 yr (n = 612), 30-39 yr (n = 140), 40-49 yr (n = 95), 50-59 yr (n = 61), and >60 yr (n = 72)]. Spontaneous baroreflex function was assessed in the time domain (bradycardic and tachycardic slope) and in the frequency domain in the low- and high-frequency band (LF-a, HF-a) applying the transfer function. General linear models showed a significant effect of factor age (P < 0.001) and an age - sex interaction effect (P < 0.05) on each indicator of the baroreflex function. Simple main effects showed a significantly higher BRS as indicated by tachycardic slope, LF-a and HF-a in middle-aged women compared with men (30-39 yr) and higher LF-a, bradycardic and tachycardic slope in men compared with women of the oldest age group (>60 yr). Changes in BRS over the lifespan suggest that baroreflex function declines more slowly but earlier in life in men than in women. Our findings could be linked to age-related changes in major sex hormone levels, suggesting significant implications for diverse cardiovascular outcomes and the implementation of targeted preventive strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Change in body weight of older adults before and during the COVID-19 pandemic: Longitudinal results from the Berlin Aging Study II

Author

Vetter, Valentin Max, primary, Drewelies, Johanna, additional, Düzel, Sandra, additional, Homann, Jan, additional, Meyer-Arndt, Lil, additional, Braun, Julian, additional, Pohrt, Anne, additional, Kendel, Friederike, additional, Wagner, Gert G., additional, Thiel, Andreas, additional, Bertram, Lars, additional, Regitz-Zagrosek, Vera, additional, Gerstorf, Denis, additional, and Demuth, Ilja, additional

Published
2023
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47. High Thyroid-Stimulating Hormone and Low Free Triiodothyronine Levels Are Associated with Chronic Kidney Disease in Three Population-Based Studies from Germany

Author

Ittermann, Till, primary, von Rheinbaben, Sabrina, additional, Markus, Marcello R. P., additional, Dörr, Marcus, additional, Steveling, Antje, additional, Nauck, Matthias, additional, Teumer, Alexander, additional, Gollasch, Maik, additional, Spira, Dominik, additional, König, Maximilian, additional, Demuth, Ilja, additional, Steinhagen-Thiessen, Elisabeth, additional, Völzke, Henry, additional, and Stracke, Sylvia, additional

Published
2023
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