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1. Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer’s disease

Author

Frick, Elisabet A., Emilsson, Valur, Jonmundsson, Thorarinn, Steindorsdottir, Anna E., Johnson, Erik C. B., Puerta, Raquel, Dammer, Eric B., Shantaraman, Anantharaman, Cano, Amanda, Boada, Mercè, Valero, Sergi, García-González, Pablo, Gudmundsson, Elias F., Gudjonsson, Alexander, Pitts, Rebecca, Qiu, Xiazi, Finkel, Nancy, Loureiro, Joseph J., Orth, Anthony P., Seyfried, Nicholas T., Levey, Allan I., Ruiz, Agustin, Aspelund, Thor, Jennings, Lori L., Launer, Lenore J., Gudmundsdottir, Valborg, and Gudnason, Vilmundur

Published
2024
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2. Adipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality

Author

Wang, Rongling, Gomez Salazar, Mario, Pruñonosa Cervera, Iris, Coutts, Amanda, French, Karen, Pinto, Marlene Magalhaes, Gohlke, Sabrina, García-Martín, Ruben, Blüher, Matthias, Schofield, Christopher J., Kourtzelis, Ioannis, Stimson, Roland H., Bénézech, Cécile, Christian, Mark, Schulz, Tim J., Gudmundsson, Elias F., Jennings, Lori L., Gudnason, Vilmundur G., Chavakis, Triantafyllos, Morton, Nicholas M., Emilsson, Valur, and Michailidou, Zoi

Published
2024
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4. Author Correction: Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer’s disease

Author

Frick, Elisabet A., Emilsson, Valur, Jonmundsson, Thorarinn, Steindorsdottir, Anna E., Johnson, Erik C. B., Puerta, Raquel, Dammer, Eric B., Shantaraman, Anantharaman, Cano, Amanda, Boada, Mercè, Valero, Sergi, García-González, Pablo, Gudmundsson, Elias F., Gudjonsson, Alexander, Pitts, Rebecca, Qiu, Xiazi, Finkel, Nancy, Loureiro, Joseph J., Orth, Anthony P., Seyfried, Nicholas T., Levey, Allan I., Ruiz, Agustin, Aspelund, Thor, Jennings, Lori L., Launer, Lenore J., Gudmundsdottir, Valborg, and Gudnason, Vilmundur

Published
2024
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5. Identification of circulating proteins associated with general cognitive function among middle-aged and older adults

Author

Tin, Adrienne, Fohner, Alison E, Yang, Qiong, Brody, Jennifer A, Davies, Gail, Yao, Jie, Liu, Dan, Caro, Ilana, Lindbohm, Joni V, Duggan, Michael R, Meirelles, Osorio, Harris, Sarah E, Gudmundsdottir, Valborg, Taylor, Adele M, Henry, Albert, Beiser, Alexa S, Shojaie, Ali, Coors, Annabell, Fitzpatrick, Annette L, Langenberg, Claudia, Satizabal, Claudia L, Sitlani, Colleen M, Wheeler, Eleanor, Tucker-Drob, Elliot M, Bressler, Jan, Coresh, Josef, Bis, Joshua C, Candia, Julián, Jennings, Lori L, Pietzner, Maik, Lathrop, Mark, Lopez, Oscar L, Redmond, Paul, Gerszten, Robert E, Rich, Stephen S, Heckbert, Susan R, Austin, Thomas R, Hughes, Timothy M, Tanaka, Toshiko, Emilsson, Valur, Vasan, Ramachandran S, Guo, Xiuqing, Zhu, Yineng, Tzourio, Christophe, Rotter, Jerome I, Walker, Keenan A, Ferrucci, Luigi, Kivimäki, Mika, Breteler, Monique MB, Cox, Simon R, Debette, Stephanie, Mosley, Thomas H, Gudnason, Vilmundur G, Launer, Lenore J, Psaty, Bruce M, Seshadri, Sudha, and Fornage, Myriam

Subjects
Biochemistry and Cell Biology, Biological Sciences, Brain Disorders, Dementia, Neurodegenerative, Acquired Cognitive Impairment, Aging, Alzheimer's Disease, Clinical Research, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Middle Aged, Humans, Aged, Alzheimer Disease, Cognition, Cognitive Dysfunction, Neurons, Biomarkers, Biological sciences, Biomedical and clinical sciences
Abstract

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p

Published
2023

6. Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk

Author

Walker, Keenan A, Chen, Jingsha, Zhang, Jingning, Fornage, Myriam, Yang, Yunju, Zhou, Linda, Grams, Morgan E, Tin, Adrienne, Daya, Natalie, Hoogeveen, Ron C, Wu, Aozhou, Sullivan, Kevin J, Ganz, Peter, Zeger, Scott L, Gudmundsson, Elias F, Emilsson, Valur, Launer, Lenore J, Jennings, Lori L, Gudnason, Vilmundur, Chatterjee, Nilanjan, Gottesman, Rebecca F, Mosley, Thomas H, Boerwinkle, Eric, Ballantyne, Christie M, and Coresh, Josef

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Acquired Cognitive Impairment, Neurodegenerative, Prevention, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Clinical Research, Brain Disorders, Biotechnology, Neurosciences, Alzheimer's Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Humans, Aged, Proteomics, Alzheimer Disease, Brain, Proteome, Clinical sciences
Abstract

The plasma proteomic changes that precede the onset of dementia could yield insights into disease biology and highlight new biomarkers and avenues for intervention. We quantified 4,877 plasma proteins in nondemented older adults in the Atherosclerosis Risk in Communities cohort and performed a proteome-wide association study of dementia risk over five years (n = 4,110; 428 incident cases). Thirty-eight proteins were associated with incident dementia after Bonferroni correction. Of these, 16 were also associated with late-life dementia risk when measured in plasma collected nearly 20 years earlier, during mid-life. Two-sample Mendelian randomization causally implicated two dementia-associated proteins (SVEP1 and angiostatin) in Alzheimer's disease. SVEP1, an immunologically relevant cellular adhesion protein, was found to be part of larger dementia-associated protein networks, and circulating levels were associated with atrophy in brain regions vulnerable to Alzheimer's pathology. Pathway analyses for the broader set of dementia-associated proteins implicated immune, lipid, metabolic signaling and hemostasis pathways in dementia pathogenesis.

Published
2021

8. A proteogenomic signature of age-related macular degeneration in blood

Author

Emilsson, Valur, Gudmundsson, Elias F., Jonmundsson, Thorarinn, Jonsson, Brynjolfur G., Twarog, Michael, Gudmundsdottir, Valborg, Li, Zhiguang, Finkel, Nancy, Poor, Stephen, Liu, Xin, Esterberg, Robert, Zhang, Yiyun, Jose, Sandra, Huang, Chia-Ling, Liao, Sha-Mei, Loureiro, Joseph, Zhang, Qin, Grosskreutz, Cynthia L., Nguyen, Andrew A., Huang, Qian, Leehy, Barrett, Pitts, Rebecca, Aspelund, Thor, Lamb, John R., Jonasson, Fridbert, Launer, Lenore J., Cotch, Mary Frances, Jennings, Lori L., Gudnason, Vilmundur, and Walshe, Tony E.

Published
2022
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11. Co-regulatory networks of human serum proteins link genetics to disease

Author

Emilsson, Valur, Ilkov, Marjan, Lamb, John R, Finkel, Nancy, Gudmundsson, Elias F, Pitts, Rebecca, Hoover, Heather, Gudmundsdottir, Valborg, Horman, Shane R, Aspelund, Thor, Shu, Le, Trifonov, Vladimir, Sigurdsson, Sigurdur, Manolescu, Andrei, Zhu, Jun, Olafsson, Örn, Jakobsdottir, Johanna, Lesley, Scott A, To, Jeremy, Zhang, Jia, Harris, Tamara B, Launer, Lenore J, Zhang, Bin, Eiriksdottir, Gudny, Yang, Xia, Orth, Anthony P, Jennings, Lori L, and Gudnason, Vilmundur

Subjects
Biochemistry and Cell Biology, Biological Sciences, Biotechnology, Genetics, Cardiovascular, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Generic health relevance, Aptamers, Nucleotide, Blood Proteins, Cardiovascular Diseases, Genetic Predisposition to Disease, Genetic Variation, Humans, Iceland, Metabolic Diseases, Metabolic Networks and Pathways, Proteome, Proteomics, General Science & Technology
Abstract

Proteins circulating in the blood are critical for age-related disease processes; however, the serum proteome has remained largely unexplored. To this end, 4137 proteins covering most predicted extracellular proteins were measured in the serum of 5457 Icelanders over 65 years of age. Pairwise correlation between proteins as they varied across individuals revealed 27 different network modules of serum proteins, many of which were associated with cardiovascular and metabolic disease states, as well as overall survival. The protein modules were controlled by cis- and trans-acting genetic variants, which in many cases were also associated with complex disease. This revealed co-regulated groups of circulating proteins that incorporated regulatory control between tissues and demonstrated close relationships to past, current, and future disease states.

Published
2018

13. Proteomic analysis of Alzheimer's disease cerebrospinal fluid reveals alterations associated with APOE ε4 and atomoxetine treatment.

Author

Dammer, Eric B., Shantaraman, Anantharaman, Ping, Lingyan, Duong, Duc M., Gerasimov, Ekaterina S., Ravindran, Suda Parimala, Gudmundsdottir, Valborg, Frick, Elisabet A., Gomez, Gabriela T., Walker, Keenan A., Emilsson, Valur, Jennings, Lori L., Gudnason, Vilmundur, Western, Daniel, Cruchaga, Carlos, Lah, James J., Wingo, Thomas S., Wingo, Aliza P., Seyfried, Nicholas T., and Levey, Allan I.

Subjects
ALZHEIMER'S disease, APOLIPOPROTEIN E, CEREBROSPINAL fluid, PROTEOMICS, CEREBRAL amyloid angiopathy, TAU proteins, PATHOLOGICAL physiology
Abstract

Alzheimer's disease (AD) is currently defined by the aggregation of amyloid-β (Aβ) and tau proteins in the brain. Although biofluid biomarkers are available to measure Aβ and tau pathology, few markers are available to measure the complex pathophysiology that is associated with these two cardinal neuropathologies. Here, we characterized the proteomic landscape of cerebrospinal fluid (CSF) changes associated with Aβ and tau pathology in 300 individuals using two different proteomic technologies—tandem mass tag mass spectrometry and SomaScan. Integration of both data types allowed for generation of a robust protein coexpression network consisting of 34 modules derived from 5242 protein measurements, including disease-relevant modules associated with autophagy, ubiquitination, endocytosis, and glycolysis. Three modules strongly associated with the apolipoprotein E ε4 (APOE ε4) AD risk genotype mapped to oxidant detoxification, mitogen-associated protein kinase signaling, neddylation, and mitochondrial biology and overlapped with a previously described lipoprotein module in serum. Alterations of all three modules in blood were associated with dementia more than 20 years before diagnosis. Analysis of CSF samples from an AD phase 2 clinical trial of atomoxetine (ATX) demonstrated that abnormal elevations in the glycolysis CSF module—the network module most strongly correlated to cognitive function—were reduced by ATX treatment. Clustering of individuals based on their CSF proteomic profiles revealed heterogeneity of pathological changes not fully reflected by Aβ and tau. Editor's summary: The use of fluid biomarkers to stratify patients and monitor treatment response can facilitate the development of therapeutics for Alzheimer's disease (AD). To extend the AD marker toolkit, Dammer et al. established an integrated cerebrospinal fluid (CSF) proteomic network and showed that interconnected groups of proteins (modules) were associated with distinct disease aspects such as Aβ and tau pathology, cognitive dysfunction, or APOE E4 status. The M20 glycolysis/redox homeostasis module was elevated in AD and correlated with cognitive dysfunction. M20 was reduced after atomoxetine treatment in CSF from patients participating in a clinical trial. Together, these results could provide a useful resource for AD biomarker development. —Daniela Neuhofer [ABSTRACT FROM AUTHOR]

Published
2024
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14. Serum proteomics reveals APOE dependent and independent protein signatures in Alzheimer’s disease

Author

Gudmundsdottir, Valborg, primary, Frick, Elisabet, additional, Emilsson, Valur, additional, Jonmundsson, Thorarinn, additional, Steindorsdottir, Anna, additional, Johnson, Erik C.B., additional, Puerta, Raquel, additional, Dammer, Eric, additional, Shantaraman, Anantharaman, additional, Cano, Amanda, additional, Boada, Merce, additional, Valero, Sergi, additional, Garcia-Gonzalez, Pablo, additional, Gudmundsson, Elias, additional, Gudjonsson, Alexander, additional, Pitts, Rebecca, additional, Qiu, Xiazi, additional, Finkel, Nancy, additional, Loureiro, Joseph, additional, Orth, Anthony, additional, Seyfried, Nicholas, additional, Levey, Allan, additional, Ruiz, Agustín, additional, Aspelund, Thor, additional, Jennings, Lori, additional, Launer, Lenore, additional, and Gudnason, Vilmundur, additional

Published
2024
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15. Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.

Author

Jakobsdottir, Johanna, van der Lee, Sven J, Bis, Joshua C, Chouraki, Vincent, Li-Kroeger, David, Yamamoto, Shinya, Grove, Megan L, Naj, Adam, Vronskaya, Maria, Salazar, Jose L, DeStefano, Anita L, Brody, Jennifer A, Smith, Albert V, Amin, Najaf, Sims, Rebecca, Ibrahim-Verbaas, Carla A, Choi, Seung-Hoan, Satizabal, Claudia L, Lopez, Oscar L, Beiser, Alexa, Ikram, M Arfan, Garcia, Melissa E, Hayward, Caroline, Varga, Tibor V, Ripatti, Samuli, Franks, Paul W, Hallmans, Göran, Rolandsson, Olov, Jansson, Jan-Håkon, Porteous, David J, Salomaa, Veikko, Eiriksdottir, Gudny, Rice, Kenneth M, Bellen, Hugo J, Levy, Daniel, Uitterlinden, Andre G, Emilsson, Valur, Rotter, Jerome I, Aspelund, Thor, Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, Alzheimer’s Disease Genetic Consortium, Genetic and Environmental Risk in Alzheimer’s Disease consortium, O'Donnell, Christopher J, Fitzpatrick, Annette L, Launer, Lenore J, Hofman, Albert, Wang, Li-San, Williams, Julie, Schellenberg, Gerard D, Boerwinkle, Eric, Psaty, Bruce M, Seshadri, Sudha, Shulman, Joshua M, Gudnason, Vilmundur, and van Duijn, Cornelia M

Subjects
Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, Alzheimer’s Disease Genetic Consortium, Genetic and Environmental Risk in Alzheimer’s Disease consortium, Animals, Humans, Drosophila melanogaster, Alzheimer Disease, Intracellular Signaling Peptides and Proteins, Amyloid beta-Protein Precursor, Apolipoproteins E, Tropomyosin, Drosophila Proteins, Membrane Proteins, Genomics, Age of Onset, Phenotype, Mutation, Alleles, Aged, European Continental Ancestry Group, Iceland, Female, Male, Receptors, Notch, Genome-Wide Association Study, Exome, Receptors, Notch, Genetics, Developmental Biology
Abstract

We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus

Published
2016

16. 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

17. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.

Author

Postmus, Iris, Trompet, Stella, Deshmukh, Harshal A, Barnes, Michael R, Li, Xiaohui, Warren, Helen R, Chasman, Daniel I, Zhou, Kaixin, Arsenault, Benoit J, Donnelly, Louise A, Wiggins, Kerri L, Avery, Christy L, Griffin, Paula, Feng, QiPing, Taylor, Kent D, Li, Guo, Evans, Daniel S, Smith, Albert V, de Keyser, Catherine E, Johnson, Andrew D, de Craen, Anton JM, Stott, David J, Buckley, Brendan M, Ford, Ian, Westendorp, Rudi GJ, Slagboom, P Eline, Sattar, Naveed, Munroe, Patricia B, Sever, Peter, Poulter, Neil, Stanton, Alice, Shields, Denis C, O'Brien, Eoin, Shaw-Hawkins, Sue, Chen, Y-D Ida, Nickerson, Deborah A, Smith, Joshua D, Dubé, Marie Pierre, Boekholdt, S Matthijs, Hovingh, G Kees, Kastelein, John JP, McKeigue, Paul M, Betteridge, John, Neil, Andrew, Durrington, Paul N, Doney, Alex, Carr, Fiona, Morris, Andrew, McCarthy, Mark I, Groop, Leif, Ahlqvist, Emma, Welcome Trust Case Control Consortium, Bis, Joshua C, Rice, Kenneth, Smith, Nicholas L, Lumley, Thomas, Whitsel, Eric A, Stürmer, Til, Boerwinkle, Eric, Ngwa, Julius S, O'Donnell, Christopher J, Vasan, Ramachandran S, Wei, Wei-Qi, Wilke, Russell A, Liu, Ching-Ti, Sun, Fangui, Guo, Xiuqing, Heckbert, Susan R, Post, Wendy, Sotoodehnia, Nona, Arnold, Alice M, Stafford, Jeanette M, Ding, Jingzhong, Herrington, David M, Kritchevsky, Stephen B, Eiriksdottir, Gudny, Launer, Leonore J, Harris, Tamara B, Chu, Audrey Y, Giulianini, Franco, MacFadyen, Jean G, Barratt, Bryan J, Nyberg, Fredrik, Stricker, Bruno H, Uitterlinden, André G, Hofman, Albert, Rivadeneira, Fernando, Emilsson, Valur, Franco, Oscar H, Ridker, Paul M, Gudnason, Vilmundur, Liu, Yongmei, Denny, Joshua C, Ballantyne, Christie M, Rotter, Jerome I, Adrienne Cupples, L, Psaty, Bruce M, Palmer, Colin NA, Tardif, Jean-Claude, and Colhoun, Helen M

Subjects
Welcome Trust Case Control Consortium, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pharmacogenetics, Polymorphism, Single Nucleotide, Cholesterol, LDL, Genome-Wide Association Study, Cholesterol, LDL, Polymorphism, Single Nucleotide
Abstract

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.

Published
2014

18. Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases.

Author

Narayanan, Manikandan, Huynh, Jimmy L, Wang, Kai, Yang, Xia, Yoo, Seungyeul, McElwee, Joshua, Zhang, Bin, Zhang, Chunsheng, Lamb, John R, Xie, Tao, Suver, Christine, Molony, Cliona, Melquist, Stacey, Johnson, Andrew D, Fan, Guoping, Stone, David J, Schadt, Eric E, Casaccia, Patrizia, Emilsson, Valur, and Zhu, Jun

Subjects
Prefrontal Cortex, Chromatin, Animals, Mice, Knockout, Humans, Mice, Huntington Disease, Dementia, Alzheimer Disease, Autopsy, Case-Control Studies, Reproducibility of Results, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, DNA (Cytosine-5-)-Methyltransferase 1, DNA (Cytosine-5-)-Methyltransferases, differential co‐expression, dysregulatory gene networks, epigenetic regulation of neural differentiation, network alignment, neurodegenerative diseases, differential co-expression, Knockout, DNA (Cytosine-5-)-Methyltransferase, Bioinformatics, Biochemistry and Cell Biology, Other Biological Sciences
Abstract

Using expression profiles from postmortem prefrontal cortex samples of 624 dementia patients and non-demented controls, we investigated global disruptions in the co-regulation of genes in two neurodegenerative diseases, late-onset Alzheimer's disease (AD) and Huntington's disease (HD). We identified networks of differentially co-expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former dominant for both AD and HD and both patterns replicating in independent human cohorts of AD and aging. When aligning networks of DC patterns and physical interactions, we identified a 242-gene subnetwork enriched for independent AD/HD signatures. This subnetwork revealed a surprising dichotomy of gained/lost correlations among two inter-connected processes, chromatin organization and neural differentiation, and included DNA methyltransferases, DNMT1 and DNMT3A, of which we predicted the former but not latter as a key regulator. To validate the inter-connection of these two processes and our key regulator prediction, we generated two brain-specific knockout (KO) mice and show that Dnmt1 KO signature significantly overlaps with the subnetwork (P = 3.1 × 10(-12)), while Dnmt3a KO signature does not (P = 0.017).

Published
2014

19. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Author

Mahajan, Anubha, Go, Min Jin, Zhang, Weihua, Below, Jennifer E, Gaulton, Kyle J, Ferreira, Teresa, Horikoshi, Momoko, Johnson, Andrew D, Ng, Maggie CY, Prokopenko, Inga, Saleheen, Danish, Wang, Xu, Zeggini, Eleftheria, Abecasis, Goncalo R, Adair, Linda S, Almgren, Peter, Atalay, Mustafa, Aung, Tin, Baldassarre, Damiano, Balkau, Beverley, Bao, Yuqian, Barnett, Anthony H, Barroso, Ines, Basit, Abdul, Been, Latonya F, Beilby, John, Bell, Graeme I, Benediktsson, Rafn, Bergman, Richard N, Boehm, Bernhard O, Boerwinkle, Eric, Bonnycastle, Lori L, Burtt, Noël, Cai, Qiuyin, Campbell, Harry, Carey, Jason, Cauchi, Stephane, Caulfield, Mark, Chan, Juliana CN, Chang, Li-Ching, Chang, Tien-Jyun, Chang, Yi-Cheng, Charpentier, Guillaume, Chen, Chien-Hsiun, Chen, Han, Chen, Yuan-Tsong, Chia, Kee-Seng, Chidambaram, Manickam, Chines, Peter S, Cho, Nam H, Cho, Young Min, Chuang, Lee-Ming, Collins, Francis S, Cornelis, Marilyn C, Couper, David J, Crenshaw, Andrew T, van Dam, Rob M, Danesh, John, Das, Debashish, de Faire, Ulf, Dedoussis, George, Deloukas, Panos, Dimas, Antigone S, Dina, Christian, Doney, Alex SF, Donnelly, Peter J, Dorkhan, Mozhgan, van Duijn, Cornelia, Dupuis, Josée, Edkins, Sarah, Elliott, Paul, Emilsson, Valur, Erbel, Raimund, Eriksson, Johan G, Escobedo, Jorge, Esko, Tonu, Eury, Elodie, Florez, Jose C, Fontanillas, Pierre, Forouhi, Nita G, Forsen, Tom, Fox, Caroline, Fraser, Ross M, Frayling, Timothy M, Froguel, Philippe, Frossard, Philippe, Gao, Yutang, Gertow, Karl, Gieger, Christian, Gigante, Bruna, Grallert, Harald, Grant, George B, Groop, Leif C, Groves, Christopher J, Grundberg, Elin, Guiducci, Candace, Hamsten, Anders, Han, Bok-Ghee, Hara, Kazuo, and Hassanali, Neelam

Subjects
Biological Sciences, Genetics, Human Genome, Diabetes, Metabolic and endocrine, Alleles, Asian People, Case-Control Studies, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Humans, Polymorphism, Single Nucleotide, Risk Factors, White People, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Published
2014

20. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

Author

DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Mahajan, Anubha, Go, Min Jin, Zhang, Weihua, Below, Jennifer E, Gaulton, Kyle J, Ferreira, Teresa, Horikoshi, Momoko, Johnson, Andrew D, Ng, Maggie CY, Prokopenko, Inga, Saleheen, Danish, Wang, Xu, Zeggini, Eleftheria, Abecasis, Goncalo R, Adair, Linda S, Almgren, Peter, Atalay, Mustafa, Aung, Tin, Baldassarre, Damiano, Balkau, Beverley, Bao, Yuqian, Barnett, Anthony H, Barroso, Ines, Basit, Abdul, Been, Latonya F, Beilby, John, Bell, Graeme I, Benediktsson, Rafn, Bergman, Richard N, Boehm, Bernhard O, Boerwinkle, Eric, Bonnycastle, Lori L, Burtt, Noël, Cai, Qiuyin, Campbell, Harry, Carey, Jason, Cauchi, Stephane, Caulfield, Mark, Chan, Juliana CN, Chang, Li-Ching, Chang, Tien-Jyun, Chang, Yi-Cheng, Charpentier, Guillaume, Chen, Chien-Hsiun, Chen, Han, Chen, Yuan-Tsong, Chia, Kee-Seng, Chidambaram, Manickam, Chines, Peter S, Cho, Nam H, Cho, Young Min, Chuang, Lee-Ming, Collins, Francis S, Cornelis, Marylin C, Couper, David J, Crenshaw, Andrew T, van Dam, Rob M, Danesh, John, Das, Debashish, de Faire, Ulf, Dedoussis, George, Deloukas, Panos, Dimas, Antigone S, Dina, Christian, Doney, Alex S, Donnelly, Peter J, Dorkhan, Mozhgan, van Duijn, Cornelia, Dupuis, Josée, Edkins, Sarah, Elliott, Paul, Emilsson, Valur, Erbel, Raimund, Eriksson, Johan G, Escobedo, Jorge, Esko, Tonu, Eury, Elodie, Florez, Jose C, Fontanillas, Pierre, Forouhi, Nita G, Forsen, Tom, Fox, Caroline, Fraser, Ross M, Frayling, Timothy M, Froguel, Philippe, Frossard, Philippe, Gao, Yutang, Gertow, Karl, Gieger, Christian, Gigante, Bruna, Grallert, Harald, Grant, George B, Grrop, Leif C, and Groves, Chrisropher J

Subjects
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Risk Factors, Case-Control Studies, Polymorphism, Single Nucleotide, Alleles, Asian Continental Ancestry Group, European Continental Ancestry Group, Hispanic Americans, Genome-Wide Association Study, Diabetes Mellitus, Type 2, Polymorphism, Single Nucleotide, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Published
2014

21. A proteomic analysis of atrial fibrillation in a prospective longitudinal cohort (AGES-Reykjavik study)

Author

Jonmundsson, Thorarinn, primary, Steindorsdottir, Anna E, additional, Austin, Thomas R, additional, Frick, Elisabet A, additional, Axelsson, Gisli T, additional, Launer, Lenore, additional, Psaty, Bruce M, additional, Loureiro, Joseph, additional, Orth, Anthony P, additional, Aspelund, Thor, additional, Emilsson, Valur, additional, Floyd, James S, additional, Jennings, Lori, additional, Gudnason, Vilmundur, additional, and Gudmundsdottir, Valborg, additional

Published
2023
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22. Serum proteomics reveals APOE dependent and independent protein signatures in Alzheimer's disease

Author

Frick, Elisabet A., primary, Emilsson, Valur, additional, Jonmundsson, Thorarinn, additional, Steindorsdottir, Anna E., additional, Johnson, Erik C.B., additional, Puerta, Raquel, additional, Dammer, Eric B., additional, Shantaraman, Anantharaman, additional, Cano, Amanda, additional, Boada, Merce, additional, Valero, Sergi, additional, Garcia-Gonzalez, Pablo, additional, Gudmundsson, Elias F., additional, Gudjonsson, Alexander, additional, Loureiro, Joseph J., additional, Orth, Anthony P., additional, Seyfried, Nicholas T., additional, Levey, Allan I., additional, Ruiz, Agustin, additional, Aspelund, Thor, additional, Jennings, Lori L., additional, Launer, Lenore J., additional, Gudmundsdottir, Valborg, additional, and Gudnason, Vilmundur, additional

Published
2023
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23. Proteomic prediction of incident heart failure and its main subtypes

Author

Emilsson, Valur, primary, Jonsson, Brynjolfur G, additional, Austin, Thomas R, additional, Gudmundsdottir, Valborg, additional, Axelsson, Gisli T, additional, Frick, Elisabet A, additional, Jonmundsson, Thorarinn, additional, Steindorsdottir, Anna E, additional, Loureiro, Joseph, additional, Brody, Jennifer A, additional, Aspelund, Thor, additional, Launer, Lenore J, additional, Thorgeirsson, Gudmundur, additional, Kortekaas, Kirsten A, additional, Lindeman, Jan H, additional, Orth, Anthony P, additional, Lamb, John R, additional, Psaty, Bruce M, additional, Kizer, Jorge R, additional, Jennings, Lori L, additional, and Gudnason, Vilmundur, additional

Published
2023
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24. Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat

Author

Fox, Caroline S, White, Charles C, Lohman, Kurt, Heard-Costa, Nancy, Cohen, Paul, Zhang, Yingying, Johnson, Andrew D, Emilsson, Valur, Liu, Ching-Ti, Chen, Y-D Ida, Taylor, Kent D, Allison, Matthew, Budoff, Matthew, Rotter, Jerome I, Carr, J Jeffrey, Hoffmann, Udo, Ding, Jingzhong, Cupples, L Adrienne, and Liu, Yongmei

Subjects
Biological Sciences, Genetics, Atherosclerosis, Prevention, Heart Disease, Aging, Nutrition, Obesity, Cardiovascular, Metabolic and endocrine, Adipose Tissue, Adult, Animals, Asian People, Black People, Body Fat Distribution, Body Mass Index, Calcium-Calmodulin-Dependent Protein Kinases, Coronary Disease, Female, Gene Expression Regulation, Genome-Wide Association Study, Hispanic or Latino, Humans, Intra-Abdominal Fat, Intracellular Signaling Peptides and Proteins, Male, Mice, Middle Aged, Pericardium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Tomography, X-Ray Computed, White People, CARDIoGRAM Consortium, Developmental Biology
Abstract

Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7 × 10(-08)). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution.

Published
2012

25. Diurnal variation of the human adipose transcriptome and the link to metabolic disease

Author

Loboda, Andrey, Kraft, Walter K, Fine, Bernard, Joseph, Jeffrey, Nebozhyn, Michael, Zhang, Chunsheng, He, Yudong, Yang, Xia, Wright, Christopher, Morris, Mark, Chalikonda, Ira, Ferguson, Mark, Emilsson, Valur, Leonardson, Amy, Lamb, John, Dai, Hongyue, Schadt, Eric, Greenberg, Howard E, and Lum, Pek Yee

Subjects
Nutrition, Obesity, Biotechnology, Genetics, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Affordable and Clean Energy, Medical Biochemistry and Metabolomics, Oncology and Carcinogenesis, Genetics & Heredity
Abstract

BackgroundCircadian (diurnal) rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation.MethodsThe present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted.ResultsThe results indicated that diurnal rhythm was the most significant driver of gene expression variation in the human adipose tissue, with at least 25% of the genes having had significant changes in their expression levels during the course of the day. The mRNA expression levels of core clock genes at a specific time of day were consistent across multiple subjects on different days in all three arms, indicating robust diurnal regulation irrespective of potential confounding factors. The genes essential for energy metabolism and tissue physiology were part of the diurnal signature. We hypothesize that the diurnal transition of the expression of energy metabolism genes reflects the shift in the adipose tissue from an energy-expending state in the morning to an energy-storing state in the evening. Consistent with this hypothesis, the diurnal transition was delayed by fasting and treatment with sibutramine. Finally, an in silico comparison of the diurnal signature with data from the publicly-available Connectivity Map demonstrated a significant association with transcripts that were repressed by mTOR inhibitors, suggesting a possible link between mTOR signaling, diurnal gene expression and metabolic regulation.ConclusionDiurnal rhythm plays an important role in the physiology and regulation of energy metabolism in the adipose tissue and should be considered in the selection of novel targets for the treatment of obesity and other metabolic disorders.

Published
2009

26. Proteomic prediction of incident heart failure and its main subtypes.

Author

Emilsson, Valur, Jonsson, Brynjolfur G., Austin, Thomas R., Gudmundsdottir, Valborg, Axelsson, Gisli T., Frick, Elisabet A., Jonmundsson, Thorarinn, Steindorsdottir, Anna E., Loureiro, Joseph, Brody, Jennifer A., Aspelund, Thor, Launer, Lenore J., Thorgeirsson, Gudmundur, Kortekaas, Kirsten A., Lindeman, Jan H., Orth, Anthony P., Lamb, John R., Psaty, Bruce M., Kizer, Jorge R., and Jennings, Lori L.

Subjects
*BRAIN natriuretic factor, *BLOOD proteins, *HEART failure, *PROTEOMICS, *OLDER people
Abstract

Aim: To examine the ability of serum proteins in predicting future heart failure (HF) events, including HF with reduced or preserved ejection fraction (HFrEF or HFpEF), in relation to event time, and with or without considering established HF‐associated clinical variables. Methods and results: In the prospective population‐based Age, Gene/Environment Susceptibility Reykjavik Study (AGES‐RS), 440 individuals developed HF after their first visit with a median follow‐up of 5.45 years. Among them, 167 were diagnosed with HFrEF and 188 with HFpEF. A least absolute shrinkage and selection operator regression model with non‐parametric bootstrap were used to select predictors from an analysis of 4782 serum proteins, and several pre‐established clinical parameters linked to HF. A subset of 8–10 distinct or overlapping serum proteins predicted different future HF outcomes, and C‐statistics were used to assess discrimination, revealing proteins combined with a C‐index of 0.80 for all incident HF, 0.78 and 0.80 for incident HFpEF or HFrEF, respectively. In the AGES‐RS, protein panels alone encompassed the risk contained in the clinical information and improved the performance characteristics of prediction models based on N‐terminal pro‐B‐type natriuretic peptide and clinical risk factors. Finally, the protein predictors performed particularly well close to the time of an HF event, an outcome that was replicated in the Cardiovascular Health Study. Conclusion: A small number of circulating proteins accurately predicted future HF in the AGES‐RS cohort of older adults, and they alone encompass the risk information found in a collection of clinical data. Incident HF events were predicted up to 8 years, with predictor performance significantly improving for events occurring less than 1 year ahead, a finding replicated in an external cohort study. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

Author

Okbay, Aysu, Wu, Yeda, Wang, Nancy, Jayashankar, Hariharan, Bennett, Michael, Nehzati, Seyed Moeen, Sidorenko, Julia, Kweon, Hyeokmoon, Goldman, Grant, Gjorgjieva, Tamara, Jiang, Yunxuan, Hicks, Barry, Tian, Chao, Hinds, David A., Ahlskog, Rafael, Magnusson, Patrik K. E., Oskarsson, Sven, Hayward, Caroline, Campbell, Archie, Porteous, David J., Freese, Jeremy, Herd, Pamela, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Fontana, Mark Alan, Pers, Tune H., Rietveld, Cornelius A., Chen, Guo-Bo, Emilsson, Valur, Meddens, S. Fleur W., Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Abdellaoui, Abdel, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, 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, Lahti, Jari, van der Lee, Sven J., de Leeuw, 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., Pourcain, Beate St, 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, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Joshi, Peter K., Jugessur, Astanand, Kaakinen, Marika A., Kähönen, Mika, Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Kutalik, Zoltan, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Meddens, Gerardus A., McMahon, George, Meisinger, Christa, Meitinger, Thomas, Milaneschi, Yusplitri, Milani, Lili, Montgomery, Grant W., Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, van Rooij, Frank J. A., Venturini, Cristina, Vinkhuyzen, Anna A. E., Völker, Uwe, Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johannes, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klaus, Bertram, Lars, Bisgaard, Hans, Boomsma, Dorret I., Borecki, Ingrid B., Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., van Duijn, Cornelia M., Eriksson, Johan G., Franke, Barbara, Franke, Lude, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, van der Harst, Pim, Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehtimäki, Terho, Lehrer, Steven F., Martin, Nicholas G., McGue, Matt, Metspalu, Andres, Pendleton, Neil, Penninx, Brenda W. J. H., Perola, Markus, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Yang, Jian, Esko, Tõnu, Watson, Chelsea, Jala, Jonathan, Conley, Dalton, Koellinger, Philipp D., Johannesson, Magnus, Laibson, David, Meyer, Michelle N., Lee, James J., Kong, Augustine, Yengo, Loic, Cesarini, David, Turley, Patrick, Visscher, Peter M., Beauchamp, Jonathan P., Benjamin, Daniel J., Young, Alexander I., Economics, Tinbergen Institute, Amsterdam Neuroscience - Complex Trait Genetics, 23andMe Research Team [Member of the MPIB: Tian Liu], Social Science Genetic Association Consortium, Okbay, Aysu, Wu, Yeda, Wang, Nancy, Jayashankar, Hariharan, Bennett, Michael, Moeen Nehzati, Seyed, Sidorenko, Julia, Kweon, Hyeokmoon, Goldman, Grant, Gjorgjieva, Tamara, Jiang, Yunxuan, Hicks, Barry, Tian, Chao, Hinds, David A., Ahlskog, Rafael, Magnusson, Patrik K. E., Oskarsson, Sven, Hayward, Caroline, Campbell, Archie, Porteous, David J., Freese, Jeremy, Herd, Pamela, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., Mccreight, Jennifer C., Mcintyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Fah Sathirapongsasuti, J., Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Alan Fontana, Mark, Pers, Tune H., Rietveld, Cornelius A., Chen, Guo-Bo, Emilsson, Valur, Meddens, S. Fleur W., Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Abdellaoui, Abdel, Ahluwalia, Tarunveer S., Bacelis, Jona, Baumbach, Clemen, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, MARIA PINA, Derringer, Jaime, 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, Lahti, Jari, van der Lee, Sven J., de Leeuw, 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, B??rge, 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, B??nnelykke, Klau, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Pano, 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, Halld??rsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Joshi, Peter K., Jugessur, Astanand, Kaakinen, Marika A., K??h??nen, Mika, Kanoni, Stavroula, Keltigangas-J??rvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Kutalik, Zoltan, Latvala, Antti, Launer, Lenore J., Lebreton, Ma??l P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., M??gi, Reedik, M??ki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Meddens, Gerardus A., Mcmahon, George, Meisinger, Christa, Meitinger, Thoma, Milaneschi, Yusplitri, Milani, Lili, Montgomery, Grant W., Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., R??ikk??nen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, van Rooij, Frank J. A., Venturini, Cristina, Vinkhuyzen, Anna A. E., V??lker, Uwe, V??lzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johanne, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klau, Bertram, Lar, Bisgaard, Han, Boomsma, Dorret I., Borecki, Ingrid B., B??ltmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., van Duijn, Cornelia M., Eriksson, Johan G., Franke, Barbara, Franke, Lude, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-J??rgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, van der Harst, Pim, Hoffmann, Wolfgang, Hypp??nen, Elina, Iacono, William G., Jacobsson, Bo, J??rvelin, Marjo-Riitta, J??ckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehtim??ki, Terho, Lehrer, Steven F., Martin, Nicholas G., Mcgue, Matt, Metspalu, Andre, Pendleton, Neil, Penninx, Brenda W. J. H., Perola, Marku, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, S??rensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Roy Thurik, A., Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, Andr?? G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Davey Smith, George, Hofman, Albert, Laibson, David I., Medland, Sarah E., Yang, Jian, Esko, T??nu, Watson, Chelsea, Jala, Jonathan, Conley, Dalton, Koellinger, Philipp D., Johannesson, Magnu, Laibson, David, Meyer, Michelle N., Lee, James J., Kong, Augustine, Yengo, Loic, Cesarini, David, Turley, Patrick, Visscher, Peter M., Beauchamp, Jonathan P., Benjamin, Daniel J., Young, Alexander I., VU University medical center, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, APH - Mental Health, APH - Digital Health, Schmidt, Börge (Beitragende*r), Eisele, Lewin (Beitragende*r), Jöckel, Karl-Heinz (Beitragende*r), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Research Institute for Asthma and COPD (GRIAC), Public Health Research (PHR), Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Adult Psychiatry, Applied Economics, Epidemiology, Cell biology, Econometrics, Erasmus School of Economics, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Department of Public Health, Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, Doctoral Programme in Human Behaviour, Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Diagnostics and Therapeutics, Doctoral Programme Brain & Mind, Doctoral Programme in Population Health, HUSLAB, Research Programs Unit, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, Doctoral Programme in Integrative Life Science, Doctoral Programme in Clinical Research, Department of General Practice and Primary Health Care, Johan Eriksson / Principal Investigator, Doctoral Programme in Oral Sciences, Clinicum, and Doctoral Programme in Biomedicine

Subjects
Multifactorial Inheritance, Medizin, HUMAN COMPLEX TRAITS, COHORT PROFILE, BIOBANK, GENETICS, MODELS, HEALTH, LOCI, GWAS, Polymorphism, Single Nucleotide/genetics, genome-wide-significant single-nucleotide polymorphisms (SNPs), Polymorphism, Single Nucleotide, educational attainment, Genetics, Humans, 3111 Biomedicine, ddc:610, Medical Genetics, Multifactorial Inheritance/genetics, Medicinsk genetik, Genome-Wide Association Study
Abstract

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of similar to 3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57. Karl-Oskar Lindgren ingår i gruppen Social Science Genetic Association Consortium

Published
2022

29. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

Author

Rietveld, Cornelius A., Esko, Tõnu, Davies, Gail, Pers, Tune H., Turley, Patrick, Benyamin, Beben, Chabris, Christopher F., Emilsson, Valur, Johnson, Andrew D., Lee, James J., de Leeuw, Christiaan, Marioni, Riccardo E., Medland, Sarah E., Miller, Michael B., Rostapshova, Olga, van der Lee, Sven J., Vinkhuyzen, Anna A. E., Amin, Najaf, Conley, Dalton, Derringer, Jaime, van Duijn, Cornelia M., Fehrmann, Rudolf, Franke, Lude, Glaeser, Edward L., Hansell, Narelle K., Hayward, Caroline, Iacono, William G., Ibrahim-Verbaas, Carla, Jaddoe, Vincent, Karjalainen, Juha, Laibson, David, Lichtenstein, Paul, Liewald, David C., Magnusson, Patrik K. E., Martin, Nicholas G., McGue, Matt, McMahon, George, Pedersen, Nancy L., Pinker, Steven, Porteous, David J., Posthuma, Danielle, Rivadeneira, Fernando, Smith, Blair H., Starr, John M., Tiemeier, Henning, Timpson, Nicholas J., Trzaskowski, Maciej, Uitterlinden, André G., Verhulst, Frank C., Ward, Mary E., Wright, Margaret J., Smith, George Davey, Deary, Ian J., Johannesson, Magnus, Plomin, Robert, Visscher, Peter M., Benjamin, Daniel J., Cesarini, David, and Koellinger, Philipp D.

Published
2014

30. Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness

Author

Morton, Nicholas M., Beltram, Jasmina, Carter, Roderick N., Michailidou, Zoi, Gorjanc, Gregor, McFadden, Clare, Barrios- Llerena, Martin E., Rodriguez-Cuenca, Sergio, Gibbins, Matthew T.G., Aird, Rhona E., Moreno-Navarrete, Jose Maria, Munger, Steven C., Svenson, Karen L., Gastaldello, Annalisa, Ramage, Lynne, Naredo, Gregorio, Zeyda, Maximilian, Wang, Zhao V., Howie, Alexander F., Saari, Aila, Sipila, Petra, Stulnig, Thomas M., Gudnason, Vilmundur, Kenyon, Christopher J., Seckl, Jonathan R., Walker, Brian R., Webster, Scott P., Dunbar, Donald R., Churchill, Gary A., Vidal-Puig, Antonio, Fernandez-Real, Jose Manuel, Emilsson, Valur, and Horvat, Simon

Subjects
Obesity -- Genetic aspects -- Development and progression, Gene expression -- Health aspects, Transferases -- Identification and classification, Biological sciences, Health
Abstract

The discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. We used the polygenic 'lean' mouse model, which has been selected for low adiposity over 60 generations, to identify mitochondrial thiosulfate sulfurtransferase (Tst; also known as rhodanese) as a candidate obesity-resistance gene with selectively increased expression in adipocytes. Elevated adipose Tst expression correlated with indices of metabolic health across diverse mouse strains. Transgenic overexpression of Tst in adipocytes protected mice from diet-induced obesity and insulin-resistant diabetes. Tst-deficient mice showed markedly exacerbated diabetes, whereas pharmacological activation of TST ameliorated diabetes in mice. Mechanistically, TST selectively augmented mitochondrial function combined with degradation of reactive oxygen species and sulfide. In humans, TST mRNA expression in adipose tissue correlated positively with insulin sensitivity in adipose tissue and negatively with fat mass. Thus, the genetic identification of Tst as a beneficial regulator of adipocyte mitochondrial function may have therapeutic significance for individuals with type 2 diabetes., Obesity prevalence seems to have plateaued at ~40% (refs. 1,2), suggesting that environmental penetrance (such as a hypercaloric diet or a sedentary lifestyle) is limited to a subpopulation of individuals [...]

Published
2016
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31. The Proteomic Profile of Interstitial Lung Abnormalities

Author

Axelsson, Gisli Thor, primary, Gudmundsson, Gunnar, additional, Pratte, Katherine A., additional, Aspelund, Thor, additional, Putman, Rachel K., additional, Sanders, Jason L., additional, Gudmundsson, Elias F., additional, Hatabu, Hiroto, additional, Gudmundsdottir, Valborg, additional, Gudjonsson, Alexander, additional, Hino, Takuya, additional, Hida, Tomoyuki, additional, Hobbs, Brian D., additional, Cho, Michael H., additional, Silverman, Edwin K., additional, Bowler, Russell P., additional, Launer, Lenore J., additional, Jennings, Lori L., additional, Hunninghake, Gary M., additional, Emilsson, Valur, additional, and Gudnason, Vilmundur, additional

Published
2022
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32. Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake

Author

Tanaka, Toshiko, Ngwa, Julius S, van Rooij, Frank JA, Zillikens, M Carola, Wojczynski, Mary K, Frazier-Wood, Alexis C, Houston, Denise K, Kanoni, Stavroula, Lemaitre, Rozenn N, Luan, Jian’an, Mikkilä, Vera, Renstrom, Frida, Sonestedt, Emily, Zhao, Jing Hua, Chu, Audrey Y, Qi, Lu, Chasman, Daniel I, de Oliveira Otto, Marcia C, Dhurandhar, Emily J, Feitosa, Mary F, Johansson, Ingegerd, Khaw, Kay-Tee, Lohman, Kurt K, Manichaikul, Ani, McKeown, Nicola M, Mozaffarian, Dariush, Singleton, Andrew, Stirrups, Kathleen, Viikari, Jorma, Ye, Zheng, Bandinelli, Stefania, Barroso, Inês, Deloukas, Panos, Forouhi, Nita G, Hofman, Albert, Liu, Yongmei, Lyytikäinen, Leo-Pekka, North, Kari E, Dimitriou, Maria, Hallmans, Goran, Kähönen, Mika, Langenberg, Claudia, Ordovas, Jose M, Uitterlinden, André G, Hu, Frank B, Kalafati, Ioanna-Panagiota, Raitakari, Olli, Franco, Oscar H, Johnson, Andrew, Emilsson, Valur, Schrack, Jennifer A, Semba, Richard D, Siscovick, David S, Arnett, Donna K, Borecki, Ingrid B, Franks, Paul W, Kritchevsky, Stephen B, Lehtimäki, Terho, Loos, Ruth JF, Orho-Melander, Marju, Rotter, Jerome I, Wareham, Nicholas J, Witteman, Jacqueline CM, Ferrucci, Luigi, Dedoussis, George, Cupples, L Adrienne, and Nettleton, Jennifer A

Published
2013
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33. Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid β and Incident Dementia

Author

Tin, Adrienne, primary, Sullivan, Kevin J., additional, Walker, Keenan A., additional, Bressler, Jan, additional, Talluri, Rajesh, additional, Yu, Bing, additional, Simino, Jeanette, additional, Gudmundsdottir, Valborg, additional, Emilsson, Valur, additional, Jennings, Lori L., additional, Launer, Lenore, additional, Mei, Hao, additional, Boerwinkle, Eric, additional, Windham, B. Gwen, additional, Gottesman, Rebecca, additional, Gudnason, Vilmundur, additional, Coresh, Josef, additional, Fornage, Myriam, additional, and Mosley, Thomas H., additional

Published
2022
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36. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Author

Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J. van, Taskesen, Erdogan, Yang, Wu, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., Mccreight, Jennifer C., Mcintyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Metspalu, Andres, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bram t, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, 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, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J. van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, 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, 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, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Mcmahon, George, Meisinger, Christa, Meitinger, Thomas, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johannes, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klaus, Bertram, Lars, Bisgaard, Hans, Borecki, Ingrid B, Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., Duijn, Cornelia M. van, Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, Harst, Pim van der, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., Mcgue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Johannesson, Magnus, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Urs, Harris, Kathleen Mullan, Hasler, Gregor, Ikram, Mohammad A., Jain, Sonia, Kessler, Ronald C., Kooyman, Maarten, Mackillop, James, Männikkö, Minna, Morcillo-Suarez, Carlos, Mcqueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthias, White, Jon, Wit, Harriet de, Fehr, Ernst, Kumari, Meena, Laibson, David, Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., Adult Psychiatry, APH - Mental Health, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Human genetics, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, 23and Me Research Team, eQTLgen Consortium, International Cannabis Consortium, Economics, Biological Psychology, Complex Trait Genetics, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Tinbergen Institute, 23andme Research Team, Psychiatric Genomics Consortium, Social Science Genetic Association Consortium, Linner Richard Karlsson, Biroli P, Kong Edward, Meddens Fleur W., Wedow Robbee, Fontana Mark Alan, Lebreton Mael, Tino Stephen P., Abdellaoui Abdel, Hammerschlag Anke R., Nivard Michel G., Okbay Aysu, Rietveld Cornelius A., Timshel Pascal N., Trzaskowski Maciej, de Vlaming Ronald, Zund Christian L., Bao Yanchun, Buzdugan Laura, Caplin Ann H., Chen Chia-Yen, Eibich Peter, Fontanillas Pierre, Gonzalez Juan R., Joshi Peter K., Karhunen Ville, Kleinman Aaron, Levin Remy Z., Lill Christina M., Meddens Gerardus A., Muntane Gerard, Sanchez-Roige Sandra, van Rooij Frank J., Taskesen Erdogan, Wu Yang, Zhang Futao, Agee Michelle, Alipanahi Babak, Bell Robert K., Bryc Katarzyna, Elson Sarah L., Furlotte Nicholas A., Huber Karen E., Litterman Nadia K., McCreight Jennifer C., McIntyre Matthew H., Mountain Joanna L., Northover Carrie A. M., Pitts Steven J., Sathirapongsasuti J. Fah, Sazonova Olga V., Shelton Janie F., Shringarpure Suyash, Tian Chao, Tung Joyce Y., Vacic Vladimir, Wilson Catherine H., Agbessi Mawusse, Ahsan Habibul, Alves Isabel, Andiappan Anand, Awadalla Philip, Battle Alexi, Beutner Frank, Bonder Marc Jan, Boomsma Dorret I., Christiansen Mark, Claringbould Annique, Deelen Patrick, Esko Tonu, Fave Marie-Julie, Franke Lude, Frayling Timothy, Gharib Sina A., Gibson Gregory, Heijmans Bastiaan, Hemani Gibran, Jansen Rick, Kahonen Mika, Kalnapenkis Anette, Kasela Silva, Kettunen Johanne, Kim Yungil, Kirsten Holger, Kovacs Peter, Krohn Knut, Kronberg-Guzman Jaanika, Kukushkina Viktorija, Kutalik Zoltan, Lee Bernett, Lehtimaki Terho, Loeffler Marku, Marigorta Urko M., Metspalu Andre, Milani Lili, Montgomery Grant W., Mueller-Nurasyid Martina, Nauck Matthia, Penninx Brenda, Perola Marku, Pervjakova Natalia, Pierce Brandon, Powell Joseph, Prokisch Holger, Psaty Bruce M., Raitakari Olli, Ring Susan, Ripatti Samuli, Rotzchke Olaf, Rueger Sina, Saha Ashi, Scholz Marku, Schramm Katharina, Seppala Ilkka, Stumvoll Michael, Sullivan Patrick, Hoen Peter-Bramt, Teumer Alexander, Thiery Joachim, Tong Lin, Tonjes Anke, van Dongen Jenny, van Meurs Joyce, Verlouw Joost, Visscher Peter M., Voelker Uwe, Vosa Urmo, Westra Harm-Jan, Yaghootkar Hanieh, Yang Jian, Zeng Biao, Lee James J., Pers Tune H., Turley Patrick, Chen Guo-Bo, Emilsson Valur, Oskarsson Sven, Pickrell Joseph K., Thom Kevin, Timshel Pascal, Ahluwalia Tarunveer S., Bacelis Jona, Baumbach Clemen, Bjornsdottir Gyda, Brandsma Johannes H., Concas Maria Pina, Derringer Jaime, 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., Kong Augustine, Lahti Jari, van der Lee Sven J., de Leeuw 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, Peyrot Wouter J., Qian Yong, Rueedi Rico, Salvi Erika, Schmidt Boerge, Schraut Katharina E., Shi Jianxin, Smith Albert V., Poot Raymond A., St Pourcain Beate, Thorleifsson Gudmar, Verweij Niek, Vuckovic Dragana, Wellmann Juergen, Yang Jingyun, Zhao Wei, Zhu Zhihong, Alizadeh Behrooz Z., Amin Najaf, Bakshi Andrew, Baumeister Sebastian E., Biino Ginevra, Bonnelykke Klau, Boyle Patricia A., Campbell Harry, Cappuccio Francesco P., Davies Gail, De Neve Jan-Emmanuel, Deloukas Pano, Demuth Ilja, Ding Jun, Eisele Lewin, Eklund Niina, Evans David M., Faul Jessica D., Feitosa Mary F., Forstner Andreas J., Gandin Ilaria, Gunnarsson Bjarni, Halldorsson Bjarni V., Harris Tamara B., Heath Andrew C., Hocking Lynne J., Holliday Elizabeth G., Homuth Georg, Horan Michael A., Hottenga Jouke-Jan, de Jager Philip L., Jugessur Astanand, Kaakinen Marika A., Kanoni Stavroula, Keltigangas-Jarvinen Liisa, Kiemeney Lambertus A. L. M., Kolcic Ivana, Koskinen Seppo, Kraja Aldi T., Kroh Martin, Latvala Antti, Launer Lenore J., Lebreton Mael P., Levinson Douglas F., Lichtenstein Paul, Lichtner Peter, Liewald David C. M., Loukola Anu, Madden Pamela A., Magi Reedik, Maki-Opas Tomi, Marioni Riccardo E., Marques-Vidal Pedro, McMahon George, Meisinger Christa, Meitinger Thoma, Milaneschi Yusplitri, Myhre Ronny, Nelson Christopher P., Nyholt Dale R., Ollier William E. R., Palotie Aarno, Paternoster Lavinia, Pedersen Nancy L., Petrovic Katja E., Porteous David J., Raikkonen Katri, Ring Susan M., Robino Antonietta, Rostapshova Olga, Rudan Igor, Rustichini Aldo, Salomaa Veikko, Sanders Alan R., Sarin Antti-Pekka, Schmidt Helena, Scott Rodney J., Smith Blair H., Smith Jennifer A., Staessen Jan A., Steinhagen-Thiessen Elisabeth, Strauch Konstantin, Terracciano Antonio, Tobin Martin D., Ulivi Sheila, Vaccargiu Simona, Quaye Lydia, Venturini Cristina, Vinkhuyzen Anna A. E., Voelzke Henry, Vonk Judith M., Vozzi Diego, Waage Johanne, Ware Erin B., Willemsen Gonneke, Attia John R., Bennett David A., Berger Klau, Bertram Lar, Bisgaard Han, Borecki Ingrid B., Bultmann Ute, Chabris Christopher F., Cucca Francesco, Cusi Daniele, Deary J., Dedoussis George V., van Duijn Cornelia M., Eriksson Johan G., Franke Barbara, Gasparini Paolo, Gejman Pablo V., Gieger Christian, Grabe Hans-Joergen, Gratten Jacob, Gudnason Vilmundur, van der Harst Pim, Hayward Caroline, Hinds David A., Hoffmann Wolfgang, Hypponen Elina, Iacono William G., Jacobsson Bo, Jarvelin Marjo-Riitta, Jockel Karl-Heinz, Kaprio Jaakko, Kardia Sharon L. R., Lehrer Steven F., Magnusson Patrik K. E., Martin Nicholas G., McGue Matt, Pendleton Neil, Pirastu Nicola, Pirastu Mario, Polasek Ozren, Posthuma Danielle, Power Christine, Province Michael A., Samani Nilesh J., Schlessinger David, Schmidt Reinhold, Sorensen Thorkild I. A., Spector Tim D., Stefansson Kari, Thorsteinsdottir Unnur, Thurik A. Roy, Timpson Nicholas J., Tiemeier Henning, Uitterlinden Andre G., Vitart Veronique, Vollenweider Peter, Weir David R., Wilson James F., Wright Alan F., Conley Dalton C., Krueger Robert F., Smith George Davey, Laibson David I., Medland Sarah E., Johannesson Magnu, Koellinger Philipp D., Cesarini David, Benjamin Daniel J., Auton Adam, Boardman Jason D., Clark David W., Conlin Andrew, Dolan Conor C., Fischbacher Ur, Groenen Patrick J. F., Harris Kathleen Mullan, Hasler Gregor, Hofman Albert, Ikram Mohammad A., Jain Sonia, Karlsson Robert, Kessler Ronald C., Kooyman Maarten, MacKillop Jame, Mannikko Minna, Morcillo-Suarez Carlo, McQueen Matthew B., Schmidt Klaus M., Smart Melissa C., Sutter Matthia, White Jon, de Wit Harriet, Fehr Ernst, Kumari Meena, Laibson David, Meyer Michelle N., Navarro Arcadi, Palmer Abraham A., Schunk Daniel, Stein Murray B., Svento Rauli, Timmers Paul R. H. J., Ursano Robert J., Wagner Gert G., Beauchamp Jonathan P., Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J. van, Taskesen, Erdogan, Wu, Yang, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., Mccreight, Jennifer C., Mcintyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexi, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johanne, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Marku, Marigorta, Urko M., Metspalu, Andre, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthia, Penninx, Brenda, Perola, Marku, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashi, Scholz, Marku, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bram t, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Ahluwalia, Tarunveer S., Bacelis, Jona, Baumbach, Clemen, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, 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, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J. van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klau, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Pano, Demuth, Ilja, Ding, Jun, 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, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Mcmahon, George, Meisinger, Christa, Meitinger, Thoma, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johanne, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klau, Bertram, Lar, Bisgaard, Han, Borecki, Ingrid B, Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., Duijn, Cornelia M. van, Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, Harst, Pim van der, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., Mcgue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Johannesson, Magnu, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Ur, Harris, Kathleen Mullan, Hasler, Gregor, Ikram, Mohammad A., Jain, Sonia, Kessler, Ronald C., Kooyman, Maarten, Mackillop, Jame, Männikkö, Minna, Morcillo-Suarez, Carlo, Mcqueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthia, White, Jon, Wit, Harriet de, Fehr, Ernst, Kumari, Meena, Laibson, David, Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., Applied Economics, Hematology, Epidemiology, Urology, Department of Marketing Management, Internal Medicine, Medical Informatics, Cell biology, Erasmus MC other, Molecular Genetics, Econometrics, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, RS: Carim - V02 Hypertension and target organ damage, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Public Health Research (PHR), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Linnér, Richard Karlsson, Biroli , Pietro, Meddens, S Fleur W, and Beauchamp, Jonathan P

Subjects
Netherlands Twin Register (NTR), Male, LD, Medizin, Poison control, Genome-wide association study, DETERMINANTS, Cathie Marsh Institute, PREFERENCES, Q1, Genome-wide association studies, HV, 0302 clinical medicine, Genetics, Behavioral/methods, GWAS, Genetics & Heredity, Genetics, 0303 health sciences, PERSONALITY, Genetic Predisposition to Disease/genetics, Behavior/physiology, Polymorphism, Single Nucleotide/genetics, 3. Good health, Manchester Institute for Collaborative Research on Ageing, Meta-analysis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Genetic Loci/genetics, Behavioural genetics, Genome-Wide Association Study/methods, Medical genetics, Female, Life Sciences & Biomedicine, Single Nucleotide/genetics, medicine.medical_specialty, ResearchInstitutes_Networks_Beacons/MICRA, Genotype, Single-nucleotide polymorphism, Genetics, Behavioral, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, ddc:330, medicine, GENDER-DIFFERENCES, SNP, Humans, Genetic Predisposition to Disease, Polymorphism, behavioural genetics, Behavioral/methods, 030304 developmental biology, Genetic association, Behavior, Science & Technology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Data Science, Case-control study, risk tolerance, GWAS, genetic architechture, Genetic Loci, Case-Control Studies, genome-wide association studies, ResearchInstitutes_Networks_Beacons/cathie_marsh_institute, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance. This research was carried out under the auspices of the Social Science Genetic Association Consortium. The research was also conducted using the UK Biobank Resource under application number 11425. The study was supported by funding from the Ragnar Söderberg Foundation (E9/11 and E42/15); the Swedish Research Council (421-2013-1061); the Jan Wallander and Tom Hedelius Foundation; an ERC Consolidator Grant to Philipp Koellinger (647648 EdGe); the Pershing Square Fund of the Foundations of Human Behavior; the Open Philanthropy Project; the National Institute on Aging, National Institutes of Health through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to the National Bureau of Economic Research and R01-AG042568-02 to the University of Southern California; the government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-152); and the Social Sciences and Humanities Research Council of Canada. We thank the International Cannabis Consortium, the eQTLgen Consortium, and the Psychiatric Genomics Consortium for sharing summary statistics from the GWAS of lifetime cannabis use, eQTL summary statistics, and summary statistics from the GWAS of ADHD, respectively. A full list of acknowledgments is provided in the Supplementary Note.

Published
2019

37. PLD3 variants in population studies

Author

van der Lee, Sven J., Holstege, Henne, Wong, Tsz Hang, Jakobsdottir, Johanna, Bis, Joshua C., Chouraki, Vincent, van Rooij, Jeroen G. J., Grove, Megan L., Smith, Albert V., Amin, Najaf, Choi, Seung-Hoan, Beiser, Alexa S., Garcia, Melissa E., van IJcken, Wilfred F. J., Pijnenburg, Yolande A. L., Louwersheimer, Eva, Brouwer, Rutger W. W., van den Hout, Mirjam C. G. N., Oole, Edwin, Eirkisdottir, Gudny, Levy, Daniel, Rotter, Jerome I., Emilsson, Valur, OʼDonnell, Christopher J., Aspelund, Thor, Uitterlinden, Andre G., Launer, Lenore J., Hofman, Albert, Boerwinkle, Eric, Psaty, Bruce M., DeStefano, Anita L., Scheltens, Philip, Seshadri, Sudha, van Swieten, John C., Gudnason, Vilmundur, van der Flier, Wiesje M., Ikram, Arfan M., and van Duijn, Cornelia M.

Published
2015
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38. Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling

Author

Ho, Jennifer E., Chen, Wei-Yu, Chen, Ming-Huei, Larson, Martin G., McCabe, Elizabeth L., Cheng, Susan, Ghorbani, Anahita, Coglianese, Erin, Emilsson, Valur, Johnson, Andrew D., Walter, Stefan, Franceschini, Nora, O'Donnell, Christopher J., Dehghan, Abbas, Lu, Chen, Levy, Daniel, Newton-Cheh, Christopher, Lin, Honghuang, Felix, Janine F., Schreiter, Eric R., Vasan, Ramachandran S., Januzzi, James L., Lee, Richard T., and Wang, Thomas J.

Subjects
Inflammation -- Research, Immune response -- Genetic aspects, Cardiovascular diseases -- Genetic aspects, Health care industry
Abstract

The suppression of tumorigenicity 2/IL-33 (ST2/IL-33) pathway has been implicated in several immune and inflammatory diseases. ST2 is produced as 2 isoforms. The membrane-bound isoform (ST2L) induces an immune response [...]

Published
2013
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39. A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance

Author

Anisul, Mohd, primary, Shilts, Jarrod, additional, Schwartzentruber, Jeremy, additional, Hayhurst, James, additional, Buniello, Annalisa, additional, Shaikho Elhaj Mohammed, Elmutaz, additional, Zheng, Jie, additional, Holmes, Michael, additional, Ochoa, David, additional, Carmona, Miguel, additional, Maranville, Joseph, additional, Gaunt, Tom R, additional, Emilsson, Valur, additional, Gudnason, Vilmundur, additional, McDonagh, Ellen M, additional, Wright, Gavin J, additional, Ghoussaini, Maya, additional, and Dunham, Ian, additional

Published
2021
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40. A Proteogenomic Signature of Age-related Macular Degeneration in Blood

Author

Emilsson, Valur, primary, Gudmundsson, Elias F., additional, Jonmundsson, Thorarinn, additional, Twarog, Michael, additional, Gudmundsdottir, Valborg, additional, Finkel, Nancy, additional, Poor, Stephen, additional, Liu, Xin, additional, Esterberg, Robert, additional, Zhang, Yiyun, additional, Jose, Sandra, additional, Huang, Chia-Ling, additional, Liao, Sha-Mei, additional, Loureiro, Joseph, additional, Zhang, Qin, additional, Grosskreutz, Cynthia L, additional, Nguyen, Andrew A, additional, Huang, Qian, additional, Leehy, Barrett, additional, Pitts, Rebecca, additional, Jonsson, Brynjolfur G., additional, Aspelund, Thor, additional, Lamb, John R., additional, Jonasson, Fridbert, additional, Launer, Lenore J., additional, Cotch, Mary Frances, additional, Jennings, Lori L., additional, Gudnason, Vilmundur, additional, and Walshe, Tony E., additional

Published
2021
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41. Author response: A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance

Author

Anisul, Mohd, primary, Shilts, Jarrod, additional, Schwartzentruber, Jeremy, additional, Hayhurst, James, additional, Buniello, Annalisa, additional, Shaikho Elhaj Mohammed, Elmutaz, additional, Zheng, Jie, additional, Holmes, Michael, additional, Ochoa, David, additional, Carmona, Miguel, additional, Maranville, Joseph, additional, Gaunt, Tom R, additional, Emilsson, Valur, additional, Gudnason, Vilmundur, additional, McDonagh, Ellen M, additional, Wright, Gavin J, additional, Ghoussaini, Maya, additional, and Dunham, Ian, additional

Published
2021
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43. Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein–protein interaction modules as robust markers of human aging

Author

van den Akker, Erik B., Passtoors, Willemijn M., Jansen, Rick, van Zwet, Erik W., Goeman, Jelle J., Hulsman, Marc, Emilsson, Valur, Perola, Markus, Willemsen, Gonneke, Penninx, Brenda W.J.H., Heijmans, Bas T., Maier, Andrea B., Boomsma, Dorret I., Kok, Joost N., Slagboom, Pieternella E., Reinders, Marcel J.T., and Beekman, Marian

Published
2014
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44. A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance

Author

Karim, Mohd A, primary, Shilts, Jarrod, additional, Schwartzentruber, Jeremy, additional, Hayhurst, James, additional, Buniello, Annalisa, additional, Mohammed, Elmutaz Shaikho Elhaj, additional, Zheng, Jie, additional, Holmes, Michael V, additional, Ochoa, David, additional, Carmona, Miguel, additional, Maranville, Joseph, additional, Gaunt, Tom R., additional, Emilsson, Valur, additional, Gudnason, Vilmundur, additional, McDonagh, Ellen M., additional, Wright, Gavin J., additional, Ghoussaini, Maya, additional, and Dunham, Ian, additional

Published
2021
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45. On the replication of genetic associations: timing can be everything!

Author

Lasky-Su, Jessica, Lyon, Helen N., Emilsson, Valur, Heid, Iris M., Molony, Cliona, Dedoussis, George, O'Donnell, Christopher J., Raby, Benjamin A., Lazarus, Ross, Klanderman, Barbara, Soto-Quiros, Manuel E., Avila, Lydiana, Wichmann, H. Erich, Celedon, Juan C., Silverman, Edwin K., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Kronenberg, Florian, Schadi, Eric, Hirschhorn, Joel, Vollmert, Caren, Illig, Thomas, Fox, Caroline S., Levy, Daniel, Laird, Nan, Xiao Ding, Weiss, Scott T., Stefansson, Kari, McQueen, Matt B., Butler, Johannah, Ardlie, Kristin, Papoutsakis, Constantina, and Lange, Christoph

Subjects
Genetic disorders -- Research, Human genome -- Research, Population genetics -- Research, Biological sciences
Abstract

The different causes that are shown to lead to the failure of replication of genetic-association findings are discussed. Findings prove that age, as well as time-related genetic effects are very important and hence should always be considered for such replications.

Published
2008

46. Variations in DNA elucidate molecular networks that cause disease

Author

Chen, Yanqing, Zhu, Jun, Lum, Pek Yee, Yang, Xia, Pinto, Shirly, Macneil, Douglas J., Zhang, Chunsheng, Lamb, John, Edwards, Stephen, Sieberts, Solveig K., Leonardson, Amy, Castellini, Lawrence W., Wang, Susana, Champy, Marie-France, Zhang, Bin, Emilsson, Valur, Doss, Sudheer, Ghazalpour, Anatole, Horvath, Steve, Drake, Thomas A., Lusis, Aldonis J., and Schadt, Eric E.

Subjects
Molecular neurobiology -- Research -- Genetic aspects, Quantitative trait loci -- Research -- Genetic aspects, Genetic variation -- Research -- Genetic aspects, Disease susceptibility -- Genetic aspects -- Research, Multifactorial traits -- Research -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation, Research, Genetic aspects
Abstract

Identifying variations in DNA that increase susceptibility to disease is one of the primary aims of genetic studies using a forward genetics approach. However, identification of disease-susceptibility genes by means [...]

Published
2008

47. Genetics of gene expression and its effect on disease

Author

Emilsson, Valur, Thorleifson, Gudmar, Zhang, Bin, Leonardson, Amy S., Zink, Florian, Zhu, Jun, Carlson, Sonia, Helgason, Agnar, Walters, G. Bragi, Gunnarsdottir, Steinunn, Mouy, Magali, Steinthorsdottir, Valgerdur, Eiriksdottir, Gudrun H., Bjornsdottir, Gyda, Reynisdottir, Inga, Gudbjartsson, Daniel, Helgadottir, Anna, Jonasdottir, Aslaug, Jonasdottir, Adalbjorg, Styrkarsdottir, Unnur, Gretarsdottir, Solveig, Magnusson, Kristinn P., Stefansson, Hreinn, Fossdal, Ragnheidur, Kristjansson, Kristleifur, Gislason, Hjortur G., Stefansson, Tryggvi, Leifsson, Bjorn G., Thorsteinsdottir, Unnur, Lamb, John R., Gulcher, Jeffrey R., Reitman, Marc L., Kong, Augustine, Schadt, Eric E., and Stefansson, Kari

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. [...]

Published
2008

48. Human serum proteome profoundly overlaps with genetic signatures of disease

Author

Emilsson, Valur, Gudmundsdottir, Valborg, Ilkov, Marjan, Staley, James R., Gudjonsson, Alexander, Gudmundsson, Elias F., Launer, Lenore J., Lindeman, Jan H., Morton, Nicholas M., Aspelund, Thor, Lamb, John R., Jennings, Lori L., and Gudnason, Vilmundur

Abstract

Circulating proteins are prognostic for human outcomes including cancer, heart failure, brain trauma and brain amyloid plaque burden. A deep serum proteome survey recently revealed close associations of serum protein networks and common diseases. The present study reveals unprecedented number of individual serum proteins that overlap genetic signatures of diseases emanating from different tissues of the body. Here, 55,932 low-frequency and common exome-array variants were compared with 4782 protein measurements in the serum of 5457 individuals of the deeply annotated AGES Reykjavik cohort. At a Bonferroni adjusted P-value threshold < 2.16×10 −10 , 5553 variants affecting levels of 1931 serum proteins were detected. These associated variants overlapped genetic loci for hundreds of complex disease traits, emphasizing the emerging role for serum proteins as biomarkers of and potential causative agents of multiple diseases.

Published
2020
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49. Adipocyte-specific deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality

Author

Salazar, Mario Gomez, primary, Cervera, Iris Pruñonosa, additional, Wang, Rongling, additional, French, Karen, additional, García-Martín, Ruben, additional, Blüher, Matthias, additional, Schofield, Christopher J, additional, Stimson, Roland H, additional, Chavakis, Triantafyllos, additional, Gudmundsson, Elias F, additional, Jennings, Lori L, additional, Gudnason, Vilmundur G, additional, Morton, Nicholas M, additional, Emilsson, Valur, additional, and Michailidou, Zoi, additional

Published
2021
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50. Serum levels of ACE2 are higher in patients with obesity and diabetes

Author

Emilsson, Valur, primary, Gudmundsson, Elias F., additional, Aspelund, Thor, additional, Jonsson, Brynjolfur G., additional, Gudjonsson, Alexander, additional, Launer, Lenore J., additional, Lamb, John R., additional, Gudmundsdottir, Valborg, additional, Jennings, Lori L., additional, and Gudnason, Vilmundur, additional

Published
2020
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