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1. Genetic architecture of ADHD and overlap with other psychiatric disorders and cognition-related phenotypes

Author: Ribasés, M., Mitjans, M., Hartman, CA, Soler Artigas, M., Demontis, D., Larsson, H., Ramos-Quiroga, JA, Kuntsi, J., Faraone, SV, Børglum, AD, Reif, A., Franke, B., and Cormand, B.
Published: 2023
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2. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.

Author: Demontis, D., Walters, G.B., Athanasiadis, G., Walters, R., Therrien, K., Nielsen, T.T., Farajzadeh, L., Voloudakis, G., Bendl, J., Zeng, B., Zhang, W, Grove, J, Als, T.D., Duan, J., Satterstrom, F.K., Bybjerg-Grauholm, J., Bækved-Hansen, M., Gudmundsson, O.O., Magnusson, S.H., Baldursson, G., Davidsdottir, K., Haraldsdottir, G.S., Agerbo, E., Hoffman, G.E., Dalsgaard, S., Martin, J., Ribasés, M., Boomsma, D.I., Soler Artigas, M., Roth Mota, N., Howrigan, D., Medland, S.E., Zayats, T., Rajagopal, V.M., Nordentoft, M., Mors, O., Hougaard, D.M., Mortensen, P.B., Daly, M.J., Faraone, S.V, Stefansson, H., Roussos, P., Franke, B., Werge, T., Neale, B.M., Stefansson, K., Børglum, A.D., Demontis, D., Walters, G.B., Athanasiadis, G., Walters, R., Therrien, K., Nielsen, T.T., Farajzadeh, L., Voloudakis, G., Bendl, J., Zeng, B., Zhang, W, Grove, J, Als, T.D., Duan, J., Satterstrom, F.K., Bybjerg-Grauholm, J., Bækved-Hansen, M., Gudmundsson, O.O., Magnusson, S.H., Baldursson, G., Davidsdottir, K., Haraldsdottir, G.S., Agerbo, E., Hoffman, G.E., Dalsgaard, S., Martin, J., Ribasés, M., Boomsma, D.I., Soler Artigas, M., Roth Mota, N., Howrigan, D., Medland, S.E., Zayats, T., Rajagopal, V.M., Nordentoft, M., Mors, O., Hougaard, D.M., Mortensen, P.B., Daly, M.J., Faraone, S.V, Stefansson, H., Roussos, P., Franke, B., Werge, T., Neale, B.M., Stefansson, K., and Børglum, A.D.
Abstract: 01 februari 2023, Item does not contain fulltext, Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.
Published: 2023

3. Genome-wide association study of school performance

Author: Soler Artigas, M., primary, Alemany, S., additional, Cabana-Domínguez, J., additional, Bosch, R., additional, Vilar-Ribó, L., additional, Llonga, N., additional, Carabí Gassol, P., additional, Ramos-Quiroga, J.A., additional, Pagerols, M., additional, Prat, R., additional, Rivas, C., additional, Español-Martín, G., additional, Casas, M., additional, and Ribasés, M., additional
Published: 2023
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4. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author: Mullins, N. Forstner, A.J. O’Connell, K.S. Coombes, B. Coleman, J.R.I. Qiao, Z. Als, T.D. Bigdeli, T.B. Børte, S. Bryois, J. Charney, A.W. Drange, O.K. Gandal, M.J. Hagenaars, S.P. Ikeda, M. Kamitaki, N. Kim, M. Krebs, K. Panagiotaropoulou, G. Schilder, B.M. Sloofman, L.G. Steinberg, S. Trubetskoy, V. Winsvold, B.S. Won, H.-H. Abramova, L. Adorjan, K. Agerbo, E. Al Eissa, M. Albani, D. Alliey-Rodriguez, N. Anjorin, A. Antilla, V. Antoniou, A. Awasthi, S. Baek, J.H. Bækvad-Hansen, M. Bass, N. Bauer, M. Beins, E.C. Bergen, S.E. Birner, A. Bøcker Pedersen, C. Bøen, E. Boks, M.P. Bosch, R. Brum, M. Brumpton, B.M. Brunkhorst-Kanaan, N. Budde, M. Bybjerg-Grauholm, J. Byerley, W. Cairns, M. Casas, M. Cervantes, P. Clarke, T.-K. Cruceanu, C. Cuellar-Barboza, A. Cunningham, J. Curtis, D. Czerski, P.M. Dale, A.M. Dalkner, N. David, F.S. Degenhardt, F. Djurovic, S. Dobbyn, A.L. Douzenis, A. Elvsåshagen, T. Escott-Price, V. Ferrier, I.N. Fiorentino, A. Foroud, T.M. Forty, L. Frank, J. Frei, O. Freimer, N.B. Frisén, L. Gade, K. Garnham, J. Gelernter, J. Giørtz Pedersen, M. Gizer, I.R. Gordon, S.D. Gordon-Smith, K. Greenwood, T.A. Grove, J. Guzman-Parra, J. Ha, K. Haraldsson, M. Hautzinger, M. Heilbronner, U. Hellgren, D. Herms, S. Hoffmann, P. Holmans, P.A. Huckins, L. Jamain, S. Johnson, J.S. Kalman, J.L. Kamatani, Y. Kennedy, J.L. Kittel-Schneider, S. Knowles, J.A. Kogevinas, M. Koromina, M. Kranz, T.M. Kranzler, H.R. Kubo, M. Kupka, R. Kushner, S.A. Lavebratt, C. Lawrence, J. Leber, M. Lee, H.-J. Lee, P.H. Levy, S.E. Lewis, C. Liao, C. Lucae, S. Lundberg, M. MacIntyre, D.J. Magnusson, S.H. Maier, W. Maihofer, A. Malaspina, D. Maratou, E. Martinsson, L. Mattheisen, M. McCarroll, S.A. McGregor, N.W. McGuffin, P. McKay, J.D. Medeiros, H. Medland, S.E. Millischer, V. Montgomery, G.W. Moran, J.L. Morris, D.W. Mühleisen, T.W. O’Brien, N. O’Donovan, C. Olde Loohuis, L.M. Oruc, L. Papiol, S. Pardiñas, A.F. Perry, A. Pfennig, A. Porichi, E. Potash, J.B. Quested, D. Raj, T. Rapaport, M.H. DePaulo, J.R. Regeer, E.J. Rice, J.P. Rivas, F. Rivera, M. Roth, J. Roussos, P. Ruderfer, D.M. Sánchez-Mora, C. Schulte, E.C. Senner, F. Sharp, S. Shilling, P.D. Sigurdsson, E. Sirignano, L. Slaney, C. Smeland, O.B. Smith, D.J. Sobell, J.L. Søholm Hansen, C. Soler Artigas, M. Spijker, A.T. Stein, D.J. Strauss, J.S. Świątkowska, B. Terao, C. Thorgeirsson, T.E. Toma, C. Tooney, P. Tsermpini, E.-E. Vawter, M.P. Vedder, H. Walters, J.T.R. Witt, S.H. Xi, S. Xu, W. Yang, J.M.K. Young, A.H. Young, H. Zandi, P.P. Zhou, H. Zillich, L. Adolfsson, R. Agartz, I. Alda, M. Alfredsson, L. Babadjanova, G. Backlund, L. Baune, B.T. Bellivier, F. Bengesser, S. Berrettini, W.H. Blackwood, D.H.R. Boehnke, M. Børglum, A.D. Breen, G. Carr, V.J. Catts, S. Corvin, A. Craddock, N. Dannlowski, U. Dikeos, D. Esko, T. Etain, B. Ferentinos, P. Frye, M. Fullerton, J.M. Gawlik, M. Gershon, E.S. Goes, F.S. Green, M.J. Grigoroiu-Serbanescu, M. Hauser, J. Henskens, F. Hillert, J. Hong, K.S. Hougaard, D.M. Hultman, C.M. Hveem, K. Iwata, N. Jablensky, A.V. Jones, I. Jones, L.A. Kahn, R.S. Kelsoe, J.R. Kirov, G. Landén, M. Leboyer, M. Lewis, C.M. Li, Q.S. Lissowska, J. Lochner, C. Loughland, C. Martin, N.G. Mathews, C.A. Mayoral, F. McElroy, S.L. McIntosh, A.M. McMahon, F.J. Melle, I. Michie, P. Milani, L. Mitchell, P.B. Morken, G. Mors, O. Mortensen, P.B. Mowry, B. Müller-Myhsok, B. Myers, R.M. Neale, B.M. Nievergelt, C.M. Nordentoft, M. Nöthen, M.M. O’Donovan, M.C. Oedegaard, K.J. Olsson, T. Owen, M.J. Paciga, S.A. Pantelis, C. Pato, C. Pato, M.T. Patrinos, G.P. Perlis, R.H. Posthuma, D. Ramos-Quiroga, J.A. Reif, A. Reininghaus, E.Z. Ribasés, M. Rietschel, M. Ripke, S. Rouleau, G.A. Saito, T. Schall, U. Schalling, M. Schofield, P.R. Schulze, T.G. Scott, L.J. Scott, R.J. Serretti, A. Shannon Weickert, C. Smoller, J.W. Stefansson, H. Stefansson, K. Stordal, E. Streit, F. Sullivan, P.F. Turecki, G. Vaaler, A.E. Vieta, E. Vincent, J.B. Waldman, I.D. Weickert, T.W. Werge, T. Wray, N.R. Zwart, J.-A. Biernacka, J.M. Nurnberger, J.I. Cichon, S. Edenberg, H.J. Stahl, E.A. McQuillin, A. Di Florio, A. Ophoff, R.A. Andreassen, O.A. HUNT All-In Psychiatry
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
Published: 2021

5. Correction to: Attention-deficit/hyperactivity disorder and lifetime cannabis use: Genetic overlap and causality

Author: Soler Artigas, M., Sánchez-Mora, C., Rovira, P., Richarte, V., Garcia-Martinez, I., Pagerols, M., Demontis, D., Stringer, S., Vink, J.M., Borglum, A.D., Neale, B.M., Franke, B., Faraone, S.V., Casas, M., Ramos-Quiroga, J.A., Ribasés, M., Soler Artigas, M., Sánchez-Mora, C., Rovira, P., Richarte, V., Garcia-Martinez, I., Pagerols, M., Demontis, D., Stringer, S., Vink, J.M., Borglum, A.D., Neale, B.M., Franke, B., Faraone, S.V., Casas, M., Ramos-Quiroga, J.A., and Ribasés, M.
Abstract: Item does not contain fulltext
Published: 2021

6. Gut microbiota signature in treatment-naïve attention-deficit/hyperactivity disorder

Author: Richarte, V., Sánchez-Mora, C., Corrales, M., Fadeuilhe, C., Vilar-Ribó, L., Arribas, L., Garcia, E., Rosales-Ortiz, S.K., Arias-Vasquez, A., Soler-Artigas, M., Ribasés, M., Ramos-Quiroga, J.A., Richarte, V., Sánchez-Mora, C., Corrales, M., Fadeuilhe, C., Vilar-Ribó, L., Arribas, L., Garcia, E., Rosales-Ortiz, S.K., Arias-Vasquez, A., Soler-Artigas, M., Ribasés, M., and Ramos-Quiroga, J.A.
Abstract: Contains fulltext : 237833.pdf (Publisher’s version ) (Open Access), Compelling evidence supports alterations in gut microbial diversity, bacterial composition, and/or relative abundance of several bacterial taxa in attention-deficit/hyperactivity disorder (ADHD). However, findings for ADHD are inconsistent among studies, and specific gut microbiome signatures for the disorder remain unknown. Given that previous studies have mainly focused on the pediatric form of the disorder and involved small sample sizes, we conducted the largest study to date to compare the gastrointestinal microbiome composition in 100 medication-naïve adults with ADHD and 100 sex-matched healthy controls. We found evidence that ADHD subjects have differences in the relative abundance of several microbial taxa. At the family level, our data support a lower relative abundance of Gracilibacteraceae and higher levels of Selenomonadaceae and Veillonellaceae in adults with ADHD. In addition, the ADHD group showed higher levels of Dialister and Megamonas and lower abundance of Anaerotaenia and Gracilibacter at the genus level. All four selected genera explained 15% of the variance of ADHD, and this microbial signature achieved an overall sensitivity of 74% and a specificity of 71% for distinguishing between ADHD patients and healthy controls. We also tested whether the selected genera correlate with age, body mass index (BMI), or scores of the ADHD rating scale but found no evidence of correlation between genera relative abundance and any of the selected traits. These results are in line with recent studies supporting gut microbiome alterations in neurodevelopment disorders, but further studies are needed to elucidate the role of the gut microbiota on the ADHD across the lifespan and its contribution to the persistence of the disorder from childhood to adulthood.
Published: 2021

7. Attention-deficit/hyperactivity disorder and lifetime cannabis use: Genetic overlap and causality

Author: Soler Artigas, M., Sánchez-Mora, C., Rovira, P., Richarte, V., Garcia-Martinez, I., Pagerols, M., Demontis, D., Stringer, S., Vink, J.M., Borglum, A.D., Neale, B.M., Franke, B., Faraone, S.V., Casas, M., Ramos-Quiroga, J.A., Ribasés, M., Soler Artigas, M., Sánchez-Mora, C., Rovira, P., Richarte, V., Garcia-Martinez, I., Pagerols, M., Demontis, D., Stringer, S., Vink, J.M., Borglum, A.D., Neale, B.M., Franke, B., Faraone, S.V., Casas, M., Ramos-Quiroga, J.A., and Ribasés, M.
Abstract: Contains fulltext : 219447.pdf (Publisher’s version ) (Closed access), Attention-deficit/hyperactivity disorder (ADHD) is a severely impairing neurodevelopmental disorder with a prevalence of 5% in children and adolescents and of 2.5% in adults. Comorbid conditions in ADHD play a key role in symptom progression, disorder course and outcome. ADHD is associated with a significantly increased risk for substance use, abuse and dependence. ADHD and cannabis use are partly determined by genetic factors; the heritability of ADHD is estimated at 70-80% and of cannabis use initiation at 40-48%. In this study, we used summary statistics from the largest available meta-analyses of genome-wide association studies (GWAS) of ADHD (n = 53,293) and lifetime cannabis use (n = 32,330) to gain insights into the genetic overlap and causal relationship of these two traits. We estimated their genetic correlation to be r2 = 0.29 (P = 1.63 x 10-5) and identified four new genome-wide significant loci in a cross-trait analysis: two in a single variant association analysis (rs145108385, P = 3.30 x 10-8 and rs4259397, P = 4.52 x 10-8) and two in a gene-based association analysis (WDPCP, P = 9.67 x 10-7 and ZNF251, P = 1.62 x 10-6). Using a two-sample Mendelian randomization approach we found support that ADHD is causal for lifetime cannabis use, with an odds ratio of 7.9 for cannabis use in individuals with ADHD in comparison to individuals without ADHD (95% CI (3.72, 15.51), P = 5.88 x 10-5). These results substantiate the temporal relationship between ADHD and future cannabis use and reinforce the need to consider substance misuse in the context of ADHD in clinical interventions.
Published: 2020

8. Genome-wide association study to identify genetic determinants of severe asthma

Author: Wan, Y I, Shrine, N R G, Soler Artigas, M, Wain, L V, Blakey, J D, Moffatt, M F, Bush, A, Chung, K F, Cookson, W O C M, Strachan, D P, Heaney, L, Al-Momani, B A H, Mansur, A H, Manney, S, Thomson, N C, Chaudhuri, R, Brightling, C E, Bafadhel, M, Singapuri, A, Niven, R, Simpson, A, Holloway, J W, Howarth, P H, Hui, J, Musk, A W, James, A L, Brown, M A, Baltic, S, Ferreira, M A R, Thompson, P J, Tobin, M D, Sayers, I, and Hall, I P
Published: 2012
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9. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author: Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), Pourcain, B.S. (Beate), Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), and Pourcain, B.S. (Beate)
Abstract: Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for lowfrequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carrie
Published: 2019
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10. Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder

Author: Pagerols M, Richarte V, Sánchez-Mora C, Rovira P, Soler Artigas M, Garcia-Martínez I, Calvo-Sánchez E, Corrales M, da Silva BS, Mota NR, Victor MM, Rohde LA, Grevet EH, Bau CHD, Cormand B, Casas M, Ramos-Quiroga JA, and Ribasés M
Subjects: mental disorders
Abstract: Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). However, a considerable interindividual variability exists in clinical outcome. Thus, we performed a genome-wide association study of MPH efficacy in 173 ADHD paediatric patients. Although no variant reached genome-wide significance, the set of genes containing single-nucleotide polymorphisms (SNPs) nominally associated with MPH response (P < 0.05) was significantly enriched for candidates previously studied in ADHD or treatment outcome. We prioritised the nominally significant SNPs by functional annotation and expression quantitative trait loci (eQTL) analysis in human brain, and we identified 33 SNPs tagging cis-eQTL in 32 different loci (referred to as eSNPs and eGenes, respectively). Pathway enrichment analyses revealed an over-representation of genes involved in nervous system development and function among the eGenes. Categories related to neurological diseases, psychological disorders and behaviour were also significantly enriched. We subsequently meta-analysed the association with clinical outcome for the 33 eSNPs across the discovery sample and an independent cohort of 189 ADHD adult patients (target sample) and we detected 15 suggestive signals. Following this comprehensive strategy, our results provide a better understanding of the molecular mechanisms implicated in MPH treatment effects and suggest promising candidates that may encourage future studies.
Published: 2018

11. Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder

Author: Pagerols, M., Richarte, Vanesa, Sanchez-Mora, Cristina, Rovira, P., Soler Artigas, M., Garcia-Martinez, Iris, Roth Mota, N., Antoni Ramos-Quiroga, Josep, Ribases, Marta, Pagerols, M., Richarte, Vanesa, Sanchez-Mora, Cristina, Rovira, P., Soler Artigas, M., Garcia-Martinez, Iris, Roth Mota, N., Antoni Ramos-Quiroga, Josep, and Ribases, Marta
Abstract: Contains fulltext : 198316.pdf (publisher's version ) (Open Access)
Published: 2018

12. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author: Hendricks, AE, Bochukova, EG, Marenne, G, Keogh, JM, Atanassova, N, Bounds, R, Wheeler, E, Mistry, V, Henning, E, Körner, A, Muddyman, D, McCarthy, S, Hinney, A, Hebebrand, J, Scott, RA, Langenberg, C, Wareham, NJ, Surendran, P, Howson, JM, Butterworth, AS, Danesh, J, Nordestgaard, BG, Nielsen, SF, Afzal, S, Papadia, S, Ashford, S, Garg, S, Millhauser, GL, Palomino, RI, Kwasniewska, A, Tachmazidou, I, O'Rahilly, S, Zeggini, E, Barroso, I, Farooqi, IS, Benzeval, M, Burton, J, Buck, N, Jäckle, A, Kumari, M, Laurie, H, Lynn, P, Pudney, S, Rabe, B, Wolke, D, Overvad, K, Tjønneland, A, Clavel-Chapelon, F, Kaaks, R, Boeing, H, Trichopoulou, A, Ferrari, P, Palli, D, Krogha, V, Panico, S, Tuminoa, R, Matullo, G, Boer, J, Van Der Schouw, Y, Weiderpass, E, Quiros, JR, Sánchez, MJ, Navarro, C, Moreno-Iribas, C, Arriola, L, Melander, O, Wennberg, P, Key, TJ, Riboli, E, Turki, SA, Anderson, CA, Anney, R, Antony, D, Soler Artigas, M, Ayub, M, Bala, S, Barrett, JC, Beales, P, Bentham, J, Bhattacharyaa, S, Birney, E, Blackwooda, D, Bobrow, M, Bolton, PF, Boustred, C, Breen, G, Calissanoa, M, Carss, K, Charlton, R, Chatterjee, K, Chen, L, Ciampia, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Coccaa, M, Collier, DA, Cosgrove, C, Coxa, T, and Crooks, Lucy
Abstract: © 2017 The Author(s). Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies.
Published: 2017

13. Gene-wide Association Study Reveals RNF122 Ubiquitin Ligase as a Novel Susceptibility Gene for Attention Deficit Hyperactivity Disorder

Author: Garcia-Martínez I, Sánchez-Mora C, Soler Artigas M, Rovira P, Pagerols M, Corrales M, Calvo-Sánchez E, Richarte V, Bustamante M, Sunyer J, Cormand B, Casas M, Ramos-Quiroga JA, and Ribasés M
Subjects: mental disorders
Abstract: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood-onset neurodevelopmental condition characterized by pervasive impairment of attention, hyperactivity, and/or impulsivity that can persist into adulthood. The aetiology of ADHD is complex and multifactorial and, despite the wealth of evidence for its high heritability, genetic studies have provided modest evidence for the involvement of specific genes and have failed to identify consistent and replicable results. Due to the lack of robust findings, we performed gene-wide and pathway enrichment analyses using pre-existing GWAS data from 607 persistent ADHD subjects and 584 controls, produced by our group. Subsequently, expression profiles of genes surpassing a follow-up threshold of P-value < 1e-03 in the gene-wide analyses were tested in peripheral blood mononucleated cells (PBMCs) of 45 medication-naive adults with ADHD and 39 healthy unrelated controls. We found preliminary evidence for genetic association between RNF122 and ADHD and for its overexpression in adults with ADHD. RNF122 encodes for an E3 ubiquitin ligase involved in the proteasome-mediated processing, trafficking, and degradation of proteins that acts as an essential mediator of the substrate specificity of ubiquitin ligation. Thus, our findings support previous data that place the ubiquitin-proteasome system as a promising candidate for its involvement in the aetiology of ADHD.
Published: 2017

14. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author: Hendricks, A.E. Bochukova, E.G. Marenne, G. Keogh, J.M. Atanassova, N. Bounds, R. Wheeler, E. Mistry, V. Henning, E. Körner, A. Muddyman, D. McCarthy, S. Hinney, A. Hebebrand, J. Scott, R.A. Langenberg, C. Wareham, N.J. Surendran, P. Howson, J.M. Butterworth, A.S. Danesh, J. Nordestgaard, Bø.G. Nielsen, S.F. Afzal, S. Papadia, S. Ashford, S. Garg, S. Millhauser, G.L. Palomino, R.I. Kwasniewska, A. Tachmazidou, I. O'Rahilly, S. Zeggini, E. Barroso, I. Farooqi, I.S. Benzeval, M. Burton, J. Buck, N. Jäckle, A. Kumari, M. Laurie, H. Lynn, P. Pudney, S. Rabe, B. Wolke, D. Overvad, K. Tjønneland, A. Clavel-Chapelon, F. Kaaks, R. Boeing, H. Trichopoulou, A. Ferrari, P. Palli, D. Krogha, V. Panico, S. Tuminoa, R. Matullo, G. Boer, J. Van Der Schouw, Y. Weiderpass, E. Quiros, J.R. Sánchez, M.-J. Navarro, C. Moreno-Iribas, C. Arriola, L. Melander, O. Wennberg, P. Key, T.J. Riboli, E. Turki, S.A. Anderson, C.A. Anney, R. Antony, D. Soler Artigas, M. Ayub, M. Bala, S. Barrett, J.C. Beales, P. Bentham, J. Bhattacharyaa, S. Birney, E. Blackwooda, D. Bobrow, M. Bolton, P.F. Boustred, C. Breen, G. Calissanoa, M. Carss, K. Charlton, R. Chatterjee, K. Chen, L. Ciampia, A. Cirak, S. Clapham, P. Clement, G. Coates, G. Coccaa, M. Collier, D.A. Cosgrove, C. Coxa, T. Craddock, N. Crooks, L. Curran, S. Curtis, D. Daly, A. Danecek, P. Day, I.N.M. Day-Williams, A. Dominiczak, A. Down, T. Du, Y. Dunham, I. Durbin, R. Edkins, S. Ekong, R. Ellis, P. Evansa, D.M. Fitzpatrick, D.R. Flicek, P. Floyd, J. Foley, A.R. Franklin, C.S. Futema, M. Gallagher, L. Gaunt, T.R. Geihs, M. Geschwind, D. Greenwood, C.M.T. Griffin, H. Grozeva, D. Guo, X. Guo, X. Gurling, H. Hart, D. Holmans, P. Howie, B. Huang, J. Huang, L. Hubbard, T. Humphries, S.E. Hurles, M.E. Hysi, P. Iotchkova, V. Jackson, D.K. Jamshidi, Y. Joyce, C. Karczewski, K.J. Kaye, J. Keane, T. Kemp, J.P. Kennedy, K. Kent, A. Khawaja, F. Van Kogelenberg, M. Kolb-Kokocinski, A. Lachance, G. Langford, C. Lawson, D. Lee, I. Lek, M. Li, R. Li, Y. Liang, J. Lin, H. Liu, R. Lönnqvist, J. Lopes, L.R. Lopes, M. MacArthur, D.G. Mangino, M. Marchini, J. Maslen, J. Mathieson, I. McGuffin, P. McIntosh, A.M. McKechanie, A.G. McQuillin, A. Memari, Y. Metrustry, S. Migone, N. Min, J.L. Mitchison, H.M. Moayyeri, A. Morris, A. Morris, J. Muntoni, F. Northstone, K. O'Donovan, M.C. Onoufriadis, A. Oualkacha, K. Owen, M.J. Palotie, A. Panoutsopoulou, K. Parker, V. Parr, J.R. Paternoster, L. Paunio, T. Payne, F. Payne, S.J. Perry, J.R.B. Pietilainen, O. Plagnol, V. Pollitt, R.C. Porteous, D.J. Povey, S. Quail, M.A. Quaye, L. Raymond, F.L. Rehnström, K. Richards, J.B. Ridout, C.K. Ring, S. Ritchie, G.R.S. Roberts, N. Robinson, R.L. Savage, D.B. Scambler, P. Schiffels, S. Schmidts, M. Schoenmakers, N. Scott, R.H. Semple, R.K. Serra, E. Sharp, S.I. Shaw, A. Shihab, H.A. Shin, S.-Y. Skuse, D. Small, K.S. Smee, C. Smith, B.H. Davey Smith, G. Soranzo, N. Southam, L. Spasic-Boskovic, O. Spector, T.D. St Clair, D. St Pourcain, B. Stalker, J. Stevens, E. Sun, J. Surdulescu, G. Suvisaari, J. Syrris, P. Taylor, R. Tian, J. Timpson, N.J. Tobin, M.D. Valdes, A.M. Vandersteen, A.M. Vijayarangakannan, P. Visscher, P.M. Wain, L.V. Walter, K. Walters, J.T.R. Wang, G. Wang, J. Wang, Y. Ward, K. Whyte, T. Williams, H.J. Williamson, K.A. Wilson, C. Wilson, S.G. Wong, K. Xu, C. Yang, J. Zhang, F. Zhang, P. Zheng, H.-F.
Abstract: Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies. © 2017 The Author(s).
Published: 2017

15. Genome-wide association study of copy number variation with lung function identifies a novel signal of association near BANP for forced vital capacity

Author: Shrine, N, Tobin, MD, Schurmann, C, Soler Artigas, M, Hui, J, Lehtimäki, T, Raitakari, OT, Pennell, CE, Ang, QW, Strachan, DP, Homuth, G, Gläser, S, Felix, SB, Evans, DM, Henderson, J, Granell, R, Palmer, LJ, Huffman, J, Hayward, C, Scotland, G, Malarstig, A, Musk, B, James, AL, UK BiLEVE, and Wain, LV
Abstract: BACKGROUND: Genome-wide association studies of Single Nucleotide Polymorphisms (SNPs) have identified 55 SNPs associated with lung function. However, little is known about the effect of copy number variants (CNVs) on lung function, although CNVs represent a significant proportion of human genetic polymorphism. To assess the effect of CNVs on lung function quantitative traits, we measured copy number at 2788 previously characterised, common copy number variable regions in 6 independent cohorts (n = 24,237) using intensity data from SNP genotyping experiments. We developed a pipeline for genome-wide association analysis and meta-analysis of CNV genotypes measured across multiple studies using SNP genotype array intensity data from different platform technologies. We then undertook cohort-level genome-wide association studies of CNV with lung function in a subset of 4 cohorts (n
Published: 2016

16. Effect of 5 Genetic Variants Associated with Lung Function on the Risk of COPD, and their Joint Effects on Lung Function

Author: Soler Artigas, M, Wain, L, Repapi, E, Obeidat, M, Sayers, I, Burton, P, Johnson, T, Zhao, J, Albrecht, E, Dominiczak, A, Kerr, S, Smith, B, Cadby, G, Hui, J, Palmer, L, Hingorani, A, Wannamethee, S, Whincup, P, Ebrahim, S, Smith, G, Barroso, I, Loos, R, Wareham, N, Cooper, C, and Dennison, E
Abstract: RATIONALE: Genomic loci are associated with forced expiratory volume in one second (FEV1) or the ratio of FEV1 to forced vital capacity (FVC) in population samples, but their association with COPD has not yet been proven, nor have their combined effects on lung function and COPD been studied. OBJECTIVES: To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER and THSD4) and evaluate joint effects on lung function and COPD of these SNPs, and variants at the previously reported locus near HHIP. METHODS: Sampling from 12 population-based studies (n=31,422), we obtained genotype data on 3,284 COPD cases and 17,538 controls for sentinel SNPs in TNS1, GSTCD, HTR4, AGER and THSD4. In 24,648 individuals (including 2,890 COPD cases and 13,862 controls), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD. RESULTS: Association with COPD was significant for three loci (TNS1, GSTCD, HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10-12 risk alleles was associated with a reduction in FEV1 (β=-72.21 ml, P=3.90x10-4) and FEV1/FVC (β=-1.53%, P=6.35x10-6), and with COPD (OR=1.63, P=1.46x10-5). CONCLUSIONS: Variants in TNS1, GSTCD and HTR4 are associated with COPD. Our highest risk score category was associated with 1.6-fold higher COPD risk than the population average score.
Published: 2016

17. Association of Forced Vital Capacity with the Developmental Gene NCOR2

Author: Minelli, C. (Cosetta), Dean, C. H. (Charlotte H.), Hind, M. (Matthew), Alves, A. C. (Alexessander Couto), Amaral, A. F. (André F. S.), Siroux, V. (Valerie), Huikari, V. (Ville), Soler Artigas, M. (María), Evans, D. M. (David M.), Loth, D. W. (Daan W.), Bossé, Y. (Yohan), Postma, D. S. (Dirkje S.), Sin, D. (Don), Thompson, J. (John), Demenais, F. (Florence), Henderson, J. (John), S. c. (SpiroMeta consortium), C. c. (CHARGE consortium), Bouzigon, E. (Emmanuelle), Jarvis, D. (Deborah), Järvelin, M.-R. (Marjo-Riitta), Burney, P. (Peter), School of Medicine / Public Health, and Latzin, Philipp
Subjects: Adult, Male, General Science & Technology, CHARGE consortium, Organogenesis, Quantitative Trait Loci, lcsh:Medicine, Young Adult, Clinical Research, Forced Expiratory Volume, Genetics, 2.1 Biological and endogenous factors, Humans, SpiroMeta consortium, Developmental, Nuclear Receptor Co-Repressor 2, Aetiology, Polymorphism, lcsh:Science, Lung, Genetic Association Studies, Aged, Gene Expression Profiling, lcsh:R, Single Nucleotide, Middle Aged, Genes, Respiratory, lcsh:Q, Female, Genome-Wide Association Study
Abstract: Article, Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (p, published version, peerReviewed
Published: 2016

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

Author: ICBP Consortium, AGEN Consortium, CHARGe-Heart Failure Group, ECHOGen Consortium, CARDIOGRAM, Abecasis, GR., Adair, LS., Alexander, M., Altshuler, D., Amin, N., Arking, DE., Arora, P., Aulchenko, Y., Bakker, SJ., Bandinelli, S., Barroso, I., Beckmann, JS., Beilby, JP., Bergman, RN., Bergmann, S., Bis, JC., Boehnke, M., Bonnycastle, LL., Bornstein, SR., Bots, ML., Bragg-Gresham, JL., Brand, SM., Brand, E., Braund, PS., Brown, MJ., Burton, PR., Casas, JP., Caulfield, MJ., Chakravarti, A., Chambers, JC., Chandak, GR., Chang, YP., Charchar, FJ., Chaturvedi, N., Shin Cho, Y., Clarke, R., Collins, FS., Collins, R., Connell, JM., Cooper, JA., Cooper, MN., Cooper, RS., Corsi, AM., Dörr, M., Dahgam, S., Danesh, J., Davey Smith, G., Day, IN., Deloukas, P., Denniff, M., Dominiczak, AF., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, FG., Fox, ER., Frayling, TM., Galan, P., Ganesh, SK., Garcia, M., Gaunt, TR., Glazer, NL., Go, MJ., Goel, A., Grässler, J., Grobbee, DE., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, BG., Hardy, R., Hartikainen, AL., Heath, S., Heckbert, SR., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, AA., Hilton, G., Hingorani, AD., Bolton, JA., Hopewell, JC., Howard, P., Humphries, SE., Hunt, SC., Hveem, K., Ikram, MA., Islam, M., Iwai, N., Jarvelin, MR., Jackson, AU., Jafar, TH., Janipalli, CS., Johnson, T., Kathiresan, S., Khaw, KT., Kim, HL., Kinra, S., Kita, Y., Kivimaki, M., Kooner, JS., Kumar, MJ., Kuh, D., Kulkarni, SR., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, EG., Langefeld, CD., Larson, MG., Lathrop, M., Lawlor, DA., Lawrence, RW., Lee, JY., Lee, NR., Levy, D., Li, Y., Longstreth, WT., Luan£££Jian'an£££ J., Lucas, G., Ludwig, B., Mangino, M., Mani, KR., Marmot, MG., Mattace-Raso, FU., Matullo, G., McArdle, WL., McKenzie, CA., Meitinger, T., Melander, O., Meneton, P., Meschia, JF., Miki, T., Milaneschi, Y., Mohlke, KL., Mooser, V., Morken, MA., Morris, RW., Mosley, TH., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, KD., Nilsson, P., Nyberg, F., O'Donnell, CJ., Ogihara, T., Ohkubo, T., Okamura, T., Ong, RT., Ongen, H., Onland-Moret, NC., O'Reilly, PF., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, LJ., Palmer, ND., Parker, AN., Peden, JF., Peltonen, L., Perola, M., Pihur, V., Platou, CG., Plump, A., Prabhakaran, D., Psaty, BM., Raffel, LJ., Rao, DC., Rasheed, A., Ricceri, F., Rice, KM., Rosengren, A., Rotter, JI., Rudock, ME., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, NJ., Schwartz, SM., Schwarz, PE., Scott, LJ., Scott, J., Scuteri, A., Sehmi, JS., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, NR., Sijbrands, EJ., Sim, X., Singleton, A., Sjögren, M., Smith, NL., Soler Artigas, M., Spector, TD., Staessen, JA., Stancakova, A., Steinle, NI., Strachan, DP., Stringham, HM., Sun, YV., Swift, AJ., Tabara, Y., Tai, ES., Talmud, PJ., Taylor, A., Terzic, J., Thelle, DS., Tobin, MD., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, CS., Umemura, S., van der Harst, P., van der Schouw YT., van Gilst WH., Vartiainen, E., Vasan, RS., Veldre, G., Verwoert, GC., Viigimaa, M., Vinay, DG., Vineis, P., Voight, BF., Vollenweider, P., Wagenknecht, LE., Wain, LV., Wang, X., Wang, TJ., Wareham, NJ., Watkins, H., Weder, AB., Whincup, PH., Wiggins, KL., Witteman, JC., Wong, A., Wu, Y., Yajnik, CS., Yao, J., Young, JH., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, JH., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, JY., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, SC., Wong, TY., Liu, J., Young, TL., Aung, T., Teo, YY., Kim, YJ., Kang, D., Chen, CH., Tsai, FJ., Chang, LC., Fann, SJ., Mei, H., Hixson, JE., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, YT., Tanaka, T., Reilly, MP., Schunkert, H., Assimes, TL., Hall, A., Hengstenberg, C., König, IR., Laaksonen, R., McPherson, R., Thompson, JR., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, LA., Halperin, E., Li, M., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, GA., Holm, H., Roberts, R., Stewart, AF., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, KJ., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, HJ., Perret, C., Proust, C., Münzel, TF., Barbalic, M., Chen, IY., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, KD., Volcik, K., Gretarsdottir, S., Gulcher, JR., Kong, A., Stefansson, K., Thorgeirsson, G., Andersen, K., Fischer, M., Grosshennig, A., Linsel-Nitschke, P., Stark, K., Schreiber, S., Aherrahrou, Z., Bruse, P., Doering, A., Klopp, N., Diemert, P., Loley, C., Medack, A., Nahrstedt, J., Peters, A., Wagner, AK., Willenborg, C., Böhm, BO., Dobnig, H., Grammer, TB., Hoffmann, MM., Meinitzer, A., Winkelmann, BR., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, SB., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Epstein, SE., Rader, DJ., Nelson, CP., Wright, BJ., Balmforth, AJ., Ball, SG., Loehr, LR., Rosamond, WD., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, YA., Stricker, BH., Chang, PP., Willerson, JT., Felix, SB., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, RJ., Greiser, KH., Deckers, JW., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, MM., Werdan, K., Mitchell, GF., Arnett, DK., Gottdiener, JS., Blettner, M., Friedrich, N., Pattaro, C., Teumer, A., Gorski, M., Chu, A.Y., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.H., Pers, T.H., Johnson, A.D., Ko, Y.A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., d'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., van der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, C.A., Hayward, C., Helmer, C., Rotimi, C.N., Shaffer, C.M., Müller, C., Sala, C., van Duijn, C.M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., Cusi, D., Czamara, D., Ellinghaus, D., Siscovick, D.S., Ruderfer, D., Gieger, C., Grallert, H., Rochtchina, E., Atkinson, E.J., Holliday, E.G., Boerwinkle, E., Salvi, E., Bottinger, E.P., Murgia, F., Rivadeneira, F., Ernst, F., Kronenberg, F., Hu, F.B., Navis, G.J., Curhan, G.C., Ehret, G.B., Homuth, G., Coassin, S., Thun, G.A., Pistis, G., Gambaro, G., Malerba, G., Montgomery, G.W., Eiriksdottir, G., Jacobs, G., Li, G., Wichmann, H.E., Campbell, H., Schmidt, H., Wallaschofski, H., Völzke, H., Brenner, H., Kroemer, H.K., Kramer, H., Lin, H., Leach, I.M., Ford, I., Guessous, I., Rudan, I., Prokopenko, I., Borecki, I., Heid, I.M., Kolcic, I., Persico, I., Jukema, J.W., Wilson, J.F., Felix, J.F., Divers, J., Lambert, J.C., Stafford, J.M., Gaspoz, J.M., Smith, J.A., Faul, J.D., Wang, J.J., Ding, J., Hirschhorn, J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., de Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L., Ulivi, S., Hwang, S.J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., de Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H., Fox, C.S., ICBP Consortium, AGEN Consortium, CHARGe-Heart Failure Group, ECHOGen Consortium, CARDIOGRAM, Abecasis, GR., Adair, LS., Alexander, M., Altshuler, D., Amin, N., Arking, DE., Arora, P., Aulchenko, Y., Bakker, SJ., Bandinelli, S., Barroso, I., Beckmann, JS., Beilby, JP., Bergman, RN., Bergmann, S., Bis, JC., Boehnke, M., Bonnycastle, LL., Bornstein, SR., Bots, ML., Bragg-Gresham, JL., Brand, SM., Brand, E., Braund, PS., Brown, MJ., Burton, PR., Casas, JP., Caulfield, MJ., Chakravarti, A., Chambers, JC., Chandak, GR., Chang, YP., Charchar, FJ., Chaturvedi, N., Shin Cho, Y., Clarke, R., Collins, FS., Collins, R., Connell, JM., Cooper, JA., Cooper, MN., Cooper, RS., Corsi, AM., Dörr, M., Dahgam, S., Danesh, J., Davey Smith, G., Day, IN., Deloukas, P., Denniff, M., Dominiczak, AF., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, FG., Fox, ER., Frayling, TM., Galan, P., Ganesh, SK., Garcia, M., Gaunt, TR., Glazer, NL., Go, MJ., Goel, A., Grässler, J., Grobbee, DE., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, BG., Hardy, R., Hartikainen, AL., Heath, S., Heckbert, SR., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, AA., Hilton, G., Hingorani, AD., Bolton, JA., Hopewell, JC., Howard, P., Humphries, SE., Hunt, SC., Hveem, K., Ikram, MA., Islam, M., Iwai, N., Jarvelin, MR., Jackson, AU., Jafar, TH., Janipalli, CS., Johnson, T., Kathiresan, S., Khaw, KT., Kim, HL., Kinra, S., Kita, Y., Kivimaki, M., Kooner, JS., Kumar, MJ., Kuh, D., Kulkarni, SR., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, EG., Langefeld, CD., Larson, MG., Lathrop, M., Lawlor, DA., Lawrence, RW., Lee, JY., Lee, NR., Levy, D., Li, Y., Longstreth, WT., Luan£££Jian'an£££ J., Lucas, G., Ludwig, B., Mangino, M., Mani, KR., Marmot, MG., Mattace-Raso, FU., Matullo, G., McArdle, WL., McKenzie, CA., Meitinger, T., Melander, O., Meneton, P., Meschia, JF., Miki, T., Milaneschi, Y., Mohlke, KL., Mooser, V., Morken, MA., Morris, RW., Mosley, TH., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, KD., Nilsson, P., Nyberg, F., O'Donnell, CJ., Ogihara, T., Ohkubo, T., Okamura, T., Ong, RT., Ongen, H., Onland-Moret, NC., O'Reilly, PF., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, LJ., Palmer, ND., Parker, AN., Peden, JF., Peltonen, L., Perola, M., Pihur, V., Platou, CG., Plump, A., Prabhakaran, D., Psaty, BM., Raffel, LJ., Rao, DC., Rasheed, A., Ricceri, F., Rice, KM., Rosengren, A., Rotter, JI., Rudock, ME., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, NJ., Schwartz, SM., Schwarz, PE., Scott, LJ., Scott, J., Scuteri, A., Sehmi, JS., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, NR., Sijbrands, EJ., Sim, X., Singleton, A., Sjögren, M., Smith, NL., Soler Artigas, M., Spector, TD., Staessen, JA., Stancakova, A., Steinle, NI., Strachan, DP., Stringham, HM., Sun, YV., Swift, AJ., Tabara, Y., Tai, ES., Talmud, PJ., Taylor, A., Terzic, J., Thelle, DS., Tobin, MD., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, CS., Umemura, S., van der Harst, P., van der Schouw YT., van Gilst WH., Vartiainen, E., Vasan, RS., Veldre, G., Verwoert, GC., Viigimaa, M., Vinay, DG., Vineis, P., Voight, BF., Vollenweider, P., Wagenknecht, LE., Wain, LV., Wang, X., Wang, TJ., Wareham, NJ., Watkins, H., Weder, AB., Whincup, PH., Wiggins, KL., Witteman, JC., Wong, A., Wu, Y., Yajnik, CS., Yao, J., Young, JH., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, JH., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, JY., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, SC., Wong, TY., Liu, J., Young, TL., Aung, T., Teo, YY., Kim, YJ., Kang, D., Chen, CH., Tsai, FJ., Chang, LC., Fann, SJ., Mei, H., Hixson, JE., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, YT., Tanaka, T., Reilly, MP., Schunkert, H., Assimes, TL., Hall, A., Hengstenberg, C., König, IR., Laaksonen, R., McPherson, R., Thompson, JR., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, LA., Halperin, E., Li, M., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, GA., Holm, H., Roberts, R., Stewart, AF., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, KJ., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, HJ., Perret, C., Proust, C., Münzel, TF., Barbalic, M., Chen, IY., 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BH., Chang, PP., Willerson, JT., Felix, SB., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, RJ., Greiser, KH., Deckers, JW., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, MM., Werdan, K., Mitchell, GF., Arnett, DK., Gottdiener, JS., Blettner, M., Friedrich, N., Pattaro, C., Teumer, A., Gorski, M., Chu, A.Y., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.H., Pers, T.H., Johnson, A.D., Ko, Y.A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., d'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., van der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, 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J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., de Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L., Ulivi, S., Hwang, S.J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., de Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H., and Fox, C.S.
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
Published: 2016

19. Effect of 5 Genetic Variants Associated with Lung Function on the Risk of COPD, and their Joint Effects on Lung Function

Author: Soler Artigas, M, Wain, LV, Repapi, E, Obeidat, M, Sayers, I, Burton, PR, Johnson, T, Zhao, JH, Albrecht, E, Dominiczak, AF, Kerr, SM, Smith, BH, Cadby, G, Hui, J, Palmer, LJ, Hingorani, AD, Wannamethee, SG, Whincup, PH, Ebrahim, S, Smith, GD, Barroso, I, Loos, RJ, Wareham, NJ, Cooper, C, Dennison, E, Shaheen, SO, Liu, JZ, Marchini, J, Dahgam, S, Naluai, AT, Olin, AC, Karrasch, S, Heinrich, J, Schulz, H, McKeever, TM, Pavord, ID, Heliövaara, M, Ripatti, S, Surakka, I, Blakey, JD, Kähönen, M, Britton, JR, Nyberg, F, Holloway, JW, Lawlor, DA, Morris, RW, James, AL, Jackson, CM, Hall, IP, and Tobin, MD
Subjects: respiratory tract diseases
Abstract: RATIONALE: Genomic loci are associated with forced expiratory volume in one second (FEV1) or the ratio of FEV1 to forced vital capacity (FVC) in population samples, but their association with COPD has not yet been proven, nor have their combined effects on lung function and COPD been studied. OBJECTIVES: To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER and THSD4) and evaluate joint effects on lung function and COPD of these SNPs, and variants at the previously reported locus near HHIP. METHODS: Sampling from 12 population-based studies (n=31,422), we obtained genotype data on 3,284 COPD cases and 17,538 controls for sentinel SNPs in TNS1, GSTCD, HTR4, AGER and THSD4. In 24,648 individuals (including 2,890 COPD cases and 13,862 controls), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD. RESULTS: Association with COPD was significant for three loci (TNS1, GSTCD, HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10-12 risk alleles was associated with a reduction in FEV1 (β=-72.21 ml, P=3.90x10-4) and FEV1/FVC (β=-1.53%, P=6.35x10-6), and with COPD (OR=1.63, P=1.46x10-5). CONCLUSIONS: Variants in TNS1, GSTCD and HTR4 are associated with COPD. Our highest risk score category was associated with 1.6-fold higher COPD risk than the population average score.
Published: 2011

20. Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function

Author: Tang, W. (Wenbo), Kowgier, M. (Matthew), Loth, D.W. (Daan), Soler Artigas, M. (Maria), Joubert, B.R. (Bonnie), Hodge, E. (Emily), Gharib, S.A. (Sina), Smith, A.V. (Davey), Ruczinski, I. (Ingo), Gudnason, V. (Vilmundur), Mathias, J. (Jasmine), Harris, T.B. (Tamara), Hansel, C.R.W. (Christian), Launer, L.J. (Lenore), Barnes, K.C. (Kathleen), Hansen, J.G. (Joyanna), Albrecht, E. (Eva), Aldrich, M.C. (Melinda), Allerhand, M.M. (Michael), Barr, R.G. (Graham), Brusselle, G.G. (Guy), Couper, D.J. (David), Curjuric, I. (Ivan), Davies, G. (Gail), Deary, I.J. (Ian), Dupuis, J. (Josée), Fall, M. (Magnus), Foy, M. (Millennia), Franceschini, N. (Nora), Gao, W. (Wei), Gläser, S. (Sven), Gu, X. (Xiangjun), Hancock, D.B. (Dana), Heinrich, J. (Joachim), Hofman, A. (Albert), Imboden, M. (Medea), Ingelsson, E. (Erik), James, A. (Alan), Karrasch, S. (Stefan), Koch, B. (Beate), Kritchevsky, S.B. (Stephen), Kumar, A. (Ashish), Lahousse, L. (Lies), Li, G. (Guo), Lind, L. (Lars), Lindgren, C.M. (Cecilia), Liu, Y. (YongMei), Lohman, K. (Kurt), Lumley, T. (Thomas), McArdle, W.L. (Wendy), Meibohm, B. (Bernd), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Musk, A.W. (Arthur), North, K.E. (Kari), Palmer, C. (Cameron), Probst-Hensch, N.M. (Nicole M.), Psaty, B.M. (Bruce), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome), Schulz, H. (Holger), Smith, L.J. (Lewis), Sood, A. (Akshay), Starr, J.M. (John), Strachan, D.P. (David), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Völzke, H. (Henry), Voorman, J.M. (Jeanine), Wain, L.V. (Louise), Wells, M.T. (Martin), Wilk, J.B. (Jemma), Williams, O.D. (Dale), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), London, S.J. (Stephanie), Fornage, M. (Myriam), Tobin, M.D. (Martin), O'Connor, G.T. (George), Hall, I.P. (Ian), Cassano, P.A. (Patricia), Tang, W. (Wenbo), Kowgier, M. (Matthew), Loth, D.W. (Daan), Soler Artigas, M. (Maria), Joubert, B.R. (Bonnie), Hodge, E. (Emily), Gharib, S.A. (Sina), Smith, A.V. (Davey), Ruczinski, I. (Ingo), Gudnason, V. (Vilmundur), Mathias, J. (Jasmine), Harris, T.B. (Tamara), Hansel, C.R.W. (Christian), Launer, L.J. (Lenore), Barnes, K.C. (Kathleen), Hansen, J.G. (Joyanna), Albrecht, E. (Eva), Aldrich, M.C. (Melinda), Allerhand, M.M. (Michael), Barr, R.G. (Graham), Brusselle, G.G. (Guy), Couper, D.J. (David), Curjuric, I. (Ivan), Davies, G. (Gail), Deary, I.J. (Ian), Dupuis, J. (Josée), Fall, M. (Magnus), Foy, M. (Millennia), Franceschini, N. (Nora), Gao, W. (Wei), Gläser, S. (Sven), Gu, X. (Xiangjun), Hancock, D.B. (Dana), Heinrich, J. (Joachim), Hofman, A. (Albert), Imboden, M. (Medea), Ingelsson, E. (Erik), James, A. (Alan), Karrasch, S. (Stefan), Koch, B. (Beate), Kritchevsky, S.B. (Stephen), Kumar, A. (Ashish), Lahousse, L. (Lies), Li, G. (Guo), Lind, L. (Lars), Lindgren, C.M. (Cecilia), Liu, Y. (YongMei), Lohman, K. (Kurt), Lumley, T. (Thomas), McArdle, W.L. (Wendy), Meibohm, B. (Bernd), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Musk, A.W. (Arthur), North, K.E. (Kari), Palmer, C. (Cameron), Probst-Hensch, N.M. (Nicole M.), Psaty, B.M. (Bruce), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome), Schulz, H. (Holger), Smith, L.J. (Lewis), Sood, A. (Akshay), Starr, J.M. (John), Strachan, D.P. (David), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Völzke, H. (Henry), Voorman, J.M. (Jeanine), Wain, L.V. (Louise), Wells, M.T. (Martin), Wilk, J.B. (Jemma), Williams, O.D. (Dale), Heckbert, S.R. (Susan), Stricker, B.H.Ch. (Bruno), London, S.J. (Stephanie), Fornage, M. (Myriam), Tobin, M.D. (Martin), O'Connor, G.T. (George), Hall, I.P. (Ian), and Cassano, P.A. (Patricia)
Published: 2014
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21. Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction

Author: Wilk, J.B. (Jemma), Shrine, N.R.G. (Nick), Loehr, L.R. (Laura), Zhao, J.H. (Jing Hua), Manichaikul, A. (Ani), Lopez, L.M. (Lorna), Smith, A.V. (Davey), Heckbert, S.R. (Susan), Smolonska, J. (Joanna), Tang, W. (Wenbo), Loth, D.W. (Daan), Curjuric, I. (Ivan), Hui, J. (Jennie), Cho, M.H. (Michael), Latourelle, J.C. (Jeanne), Henry, A. (Amanda), Aldrich, M.C. (Melinda), Bakke, A.B. (Arnold B.), Beaty, T.H. (Terri), Bentley, A.R. (Amy), Borecki, I.B. (Ingrid), Brusselle, G.G. (Guy), Burkart, K.M. (Kristin), Chen, T.H., Couper, D.J. (David), Crapo, R.O. (Robert), Davies, G. (Gail), Dupuis, J. (Josée), Franceschini, N. (Nora), Gulsvik, A. (Amund), Hancock, D.B. (Dana), Harris, T.B. (Tamara), Hofman, A. (Albert), Imboden, M. (Medea), James, A.L. (Alan), Khaw, K-T. (Kay-Tee), Lahousse, L. (Lies), Launer, L.J. (Lenore), Litonjua, A.A. (Augusto), Liu, Y. (YongMei), Lohman, K. (Kurt), Lomas, D.J. (David John), Lumley, T. (Thomas), Marciante, K. (Kristin), McArdle, W.L. (Wendy), Meibohm, B. (Bernd), Morrison, A.C. (Alanna), Musk, A.W. (Arthur), Myers, R.H. (Richard), North, K.E. (Kari), Postma, D.S. (Dirkje), Psaty, B.M. (Bruce), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Rochat, T. (Thierry), Rotter, J.I. (Jerome), Soler Artigas, M. (Maria), Starr, J.M. (John), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Wijmenga, C. (Cisca), Zanen, P. (Pieter), Province, M.A. (Mike), Silverman, E. (Edwin), Deary, I.J. (Ian), Palmer, C. (Cameron), Cassano, P.A. (Patricia), Gudnason, V. (Vilmundur), Barr, R.G. (Graham), Loos, R.J.F. (Ruth), Strachan, D.P. (David), London, S.J. (Stephanie), Boezen, H.M. (Marike), Probst-Hensch, N. (Nicole), Gharib, S.A. (Sina), Hall, I.P. (Ian), O'Connor, G.T. (George), Tobin, M.D. (Martin), Stricker, B.H.Ch. (Bruno), Wilk, J.B. (Jemma), Shrine, N.R.G. (Nick), Loehr, L.R. (Laura), Zhao, J.H. (Jing Hua), Manichaikul, A. (Ani), Lopez, L.M. (Lorna), Smith, A.V. (Davey), Heckbert, S.R. (Susan), Smolonska, J. (Joanna), Tang, W. (Wenbo), Loth, D.W. (Daan), Curjuric, I. (Ivan), Hui, J. (Jennie), Cho, M.H. (Michael), Latourelle, J.C. (Jeanne), Henry, A. (Amanda), Aldrich, M.C. (Melinda), Bakke, A.B. (Arnold B.), Beaty, T.H. (Terri), Bentley, A.R. (Amy), Borecki, I.B. (Ingrid), Brusselle, G.G. (Guy), Burkart, K.M. (Kristin), Chen, T.H., Couper, D.J. (David), Crapo, R.O. (Robert), Davies, G. (Gail), Dupuis, J. (Josée), Franceschini, N. (Nora), Gulsvik, A. (Amund), Hancock, D.B. (Dana), Harris, T.B. (Tamara), Hofman, A. (Albert), Imboden, M. (Medea), James, A.L. (Alan), Khaw, K-T. (Kay-Tee), Lahousse, L. (Lies), Launer, L.J. (Lenore), Litonjua, A.A. (Augusto), Liu, Y. (YongMei), Lohman, K. (Kurt), Lomas, D.J. (David John), Lumley, T. (Thomas), Marciante, K. (Kristin), McArdle, W.L. (Wendy), Meibohm, B. (Bernd), Morrison, A.C. (Alanna), Musk, A.W. (Arthur), Myers, R.H. (Richard), North, K.E. (Kari), Postma, D.S. (Dirkje), Psaty, B.M. (Bruce), Rich, S.S. (Stephen), Rivadeneira Ramirez, F. (Fernando), Rochat, T. (Thierry), Rotter, J.I. (Jerome), Soler Artigas, M. (Maria), Starr, J.M. (John), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Wijmenga, C. (Cisca), Zanen, P. (Pieter), Province, M.A. (Mike), Silverman, E. (Edwin), Deary, I.J. (Ian), Palmer, C. (Cameron), Cassano, P.A. (Patricia), Gudnason, V. (Vilmundur), Barr, R.G. (Graham), Loos, R.J.F. (Ruth), Strachan, D.P. (David), London, S.J. (Stephanie), Boezen, H.M. (Marike), Probst-Hensch, N. (Nicole), Gharib, S.A. (Sina), Hall, I.P. (Ian), O'Connor, G.T. (George), Tobin, M.D. (Martin), and Stricker, B.H.Ch. (Bruno)
Abstract: Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic ofCOPD assessedby spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. Methods: Fif
Published: 2012
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22. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author: Ehret, G.B. (Georg), Munroe, P. (Patricia), Rice, K.M. (Kenneth), Bochud, M. (Murielle), Johnson, A.D. (Andrew), Chasman, D.I. (Daniel), Smith, A.V. (Albert Vernon), Tobin, M.D. (Martin), Verwoert, G.C. (Germaine), Hwang, S.J., Pihur, V. (Vasyl), Vollenweider, P. (Peter), O'Reilly, P.F. (Paul), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Teumer, A. (Alexander), Glazer, N.L. (Nicole), Launer, L.J. (Lenore), Zhao, J.H. (Jing Hua), Aulchenko, Y.S. (Yurii), Heath, S.C. (Simon), Sõber, S. (Siim), Parsa, A. (Afshin), Luan, J., Arora, P. (Pankaj), Dehghan, A. (Abbas), Zhang, F. (Feng), Lucas, G. (Gavin), Hicks, A.A. (Andrew), Jackson, A.U. (Anne), Peden, J. (John), Tanaka, T. (Toshiko), Wild, S.H. (Sarah), Rudan, I. (Igor), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Parker, A.N. (Alex), Fava, C. (Cristiano), Chambers, J.C. (John), Fox, E.R. (Ervin), Kumari, M. (Meena), Jin Go, M. (Min), Harst, P. (Pim) van der, Kao, W.-H.L. (Wen-Hong Linda), Sjögren, M. (Marketa), Vinay, D.G., Alexander, M. (Myriam), Tabara, Y. (Yasuharu), Shaw-Hawkins, S. (Sue), Whincup, P.H. (Peter), Liu, Y. (YongMei), Shi, G. (Gang), Kuusisto, J. (Johanna), Tayo, B. (Bamidele), Seielstad, M. (Mark), Sim, X. (Xueling), Hoang Nguyen, K.-D., Lehtimäki, T. (Terho), Matullo, G. (Giuseppe), Wu, Y. (Ying), Gaunt, T.R. (Tom), Onland-Moret, N.C. (Charlotte), Cooper, M.N. (Matthew), Platou, C. (Carl), Org, E. (Elin), Hardy, R. (Rebecca), Dahgam, S. (Santosh), Palmen, J. (Jutta), Vitart, V. (Veronique), Braund, P.S. (Peter), Kuznetsova, T. (Tatiana), Uiterwaal, C.S.P.M. (Cuno), Adeyemo, A. (Adebowale), Palmas, W. (Walter), Campbell, H. (Harry), Ludwig, B. (Barbara), Tomaszewski, M., Tzoulaki, I., Palmer, N.D. (Nicholette), Aspelund, T. (Thor), Garcia, M. (Melissa), Chang, Y.-P.C. (Yen-Pei), O´Connell, J.R., Steinle, N.I. (Nanette), Grobbee, D.E. (Diederick), Arking, D.E. (Dan), Kardia, S.L. (Sharon), Morrison, A.C. (Alanna), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), McArdle, W.L. (Wendy), Hadley, D. (David), Brown, M.J. (Morris), Connell, J. (John), Hingorani, A. (Aroon), Day, I.N.M. (Ian), Lawlor, D.A. (Debbie), Beilby, J.P. (John), Lawrence, R.W. (Robert), Clarke, R., Hopewell, J., Ongen, H. (Halit), Dreisbach, A.W. (Albert), Li, Y. (Yali), Hunter Young, J., Bis, J.C. (Joshua), Kähönen, M. (Mika), Viikari, J. (Jorma), Lee, N.R. (Nanette), Chen, M-H. (Ming-Huei), Olden, M. (Matthias), Pattaro, C. (Cristian), Hoffman Bolton, J.A. (Judith), Köttgen, A. (Anna), Bergmann, S.M. (Sven), Mooser, V. (Vincent), Chaturvedi, N. (Nish), Frayling, T.M. (Timothy), Islam, M. (Muhammad), Jafar, T.H. (Tazeen), Kulkarni, S.R. (Smita), Bornstein, S.R. (Stefan), Gräßler, J. (Jürgen), Groop, L. (Leif), Voight, B.F. (Benjamin), Kettunen, J. (Johannes), Howard, P. (Philip), Taylor, A. (Andrew), Guarrera, S. (Simonetta), Ricceri, F. (Fulvio), Emilsson, V. (Valur), Plump, A.S. (Andrew), Khaw, K-T. (Kay-Tee), Weder, A.B. (Alan), Hunt, S.C. (Steven), Sun, Y.V. (Yan), Bergman, R.N. (Richard), Collins, F.S. (Francis), Bonnycastle, L.L. (Lori), Scott, L.J. (Laura), Stringham, H.M. (Heather), Peltonen, L. (Leena Johanna), Perola, M. (Markus), Vartiainen, E. (Erkki), Brand, S.-M., Staessen, J.A. (Jan), Wang, Y.A. (Ying), Burton, P.R. (Paul), Soler Artigas, M. (Maria), Dong, Y. (Yanbin), Snieder, H. (Harold), Zhu, H. (Haidong), Lohman, K. (Kurt), Rudock, M.E. (Megan), Heckbert, S.R. (Susan), Wiggins, K.L. (Kerri), Doumatey, A. (Ayo), Shriner, D. (Daniel), Veldre, G. (Gudrun), Viigimaa, M. (Margus), Kinra, S. (Sanjay), Prabhakaran, D. (Dorairaj), Tripathy, V. (Vikal), Langefeld, C.D. (Carl), Rosengren, A. (Annika), Thelle, D.S. (Dag), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Forrester, T. (Terrence), Hilton, G. (Gina), McKenzie, C.A. (Colin), Salako, T. (Tunde), Iwai, N. (Naoharu), Kita, Y. (Yoshikuni), Ogihara, T. (Toshio), Ohkubo, T. (Takayoshi), Okamura, T. (Tomonori), Ueshima, H. (Hirotsugu), Umemura, S. (Satoshi), Eyheramendy, S. (Susana), Meitinger, T. (Thomas), Wichmann, H.E. (Heinz Erich), Shin Cho, Y. (Yoon), Kim, H.-L., Sehmi, J.S. (Joban), Hedblad, B. (Bo), Nilsson, P. (Peter), Davey-Smith, G. (George), Wong, A. (Andrew), Narisu, N. (Narisu), Stancáková, A. (Alena), Raffel, L.J. (Leslie), Yao, J. (Jie), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Shrine, N.R.G. (Nick), Wain, L.V. (Louise), Morken, M.A. (Mario), Swift, A.J. (Amy), Laitinen, J. (Jaana), Prokopenko, I. (Inga), Zitting, P. (Paavo), Humphries, S.E. (Steve), Danesh, J. (John), Rasheed, A. (Asif), Goel, A. (Anuj), Hamsten, A. (Anders), Watkins, H. (Hugh), Gilst, W.H. (Wiek) van, Janipalli, C.S. (Charles), Radha Mani, K., Yajnik, C. (Chittaranjan), Hofman, A. (Albert), Mattace Raso, F.U.S. (Francesco), Oostra, B.A. (Ben), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Rivadeneira Ramirez, F. (Fernando), Lakatta, E. (Edward), Orrù, M. (Marco), Scuteri, A. (Angelo), Ala-Korpela, M. (Mika), Kangas, A.J. (Antti), Lyytikäinen, L.-P. (Leo-Pekka), Soininen, P. (Pasi), Tukiainen, T. (Taru), Würtz, P. (Peter), Twee-Hee Ong, R. (Rick), Dörr, M. (Marcus), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Zelenika, D. (Diana), Deloukas, P. (Panagiotis), Mangino, M. (Massimo), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meschia, J.F. (James F.), Nalls, M.A. (Michael), Sharma, P. (Pankaj), Terzic, J. (Janos), Kranthi Kumar, M.V., Denniff, M. (Matthew), Zukowska-Szczechowska, E. (Ewa), Wagenknecht, L.E. (Lynne), Fowkes, F.G.R. (Gerald), Charchar, F.J. (Fadi), Schwarz, P.E.H. (Peter), Hayward, C. (Caroline), Guo, X. (Xiuqing), Rotimi, C. (Charles), Bots, M.L. (Michiel), Samani, N.J. (Nilesh), Polasek, O. (Ozren), Talmud, P.J. (Philippa), Nyberg, F. (Fredrik), Kuh, D. (Diana), Laan, M. (Maris), Hveem, K. (Kristian), Schouw, Y.T. (Yvonne) van der, Casas, J.P. (Juan), Mohlke, K.L. (Karen), Vineis, P. (Paolo), Raitakari, O. (Olli), Ganesh, S.K. (Santhi), Shyong Tai, E., Laakso, M. (Markku), Rao, D.C. (Dabeeru C.), Harris, T.B. (Tamara), Morris, R.W. (Richard), Dominiczak, A. (Anna), Kivimaki, M. (Mika), Marmot, M. (Michael), Miki, T. (Tetsuro), Saleheen, D., Chandak, G.R. (Giriraj), Coresh, J. (Josef), Navis, G. (Gerjan), Salomaa, V. (Veikko), Han, B.-G., Kooner, J.S. (Jaspal), Melander, O. (Olle), Ridker, P.M. (Paul), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Tuomilehto, J. (Jaakko), Pramstaller, P.P. (Peter Paul), Elosua, R. (Roberto), Soranzo, N. (Nicole), Sijbrands, E.J.G. (Eric), Altshuler, D. (David), Loos, R.J.F. (Ruth), Shuldiner, A.R. (Alan), Gieger, C. (Christian), Meneton, P. (Pierre), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Gudnason, V. (Vilmundur), Rotter, J.I. (Jerome), Rettig, R. (Rainer), Uda, M. (Manuela), Strachan, D.P. (David), Witteman, J.C.M. (Jacqueline), Hartikainen, A.L., Beckmann, J.S. (Jacques), Boerwinkle, E.A. (Eric), Erdmann, J. (Jeanette), Vasan, R.S. (Ramachandran Srini), Boehnke, M. (Michael), Larson, M.G. (Martin), Järvelin, M.R., Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Newton-Cheh, C. (Christopher), Elliott, P. (Paul), Levy, D. (Daniel), Caulfield, M. (Mark), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda), Bakker, S.J.L. (Stephan), Barroso, I.E. (Inês), Ehret, G.B. (Georg), Munroe, P. (Patricia), Rice, K.M. (Kenneth), Bochud, M. (Murielle), Johnson, A.D. (Andrew), Chasman, D.I. (Daniel), Smith, A.V. (Albert Vernon), Tobin, M.D. (Martin), Verwoert, G.C. (Germaine), Hwang, S.J., Pihur, V. (Vasyl), Vollenweider, P. (Peter), O'Reilly, P.F. (Paul), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Teumer, A. (Alexander), Glazer, N.L. (Nicole), Launer, L.J. (Lenore), Zhao, J.H. (Jing Hua), Aulchenko, Y.S. (Yurii), Heath, S.C. (Simon), Sõber, S. (Siim), Parsa, A. (Afshin), Luan, J., Arora, P. (Pankaj), Dehghan, A. (Abbas), Zhang, F. (Feng), Lucas, G. (Gavin), Hicks, A.A. (Andrew), Jackson, A.U. (Anne), Peden, J. (John), Tanaka, T. (Toshiko), Wild, S.H. (Sarah), Rudan, I. (Igor), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Parker, A.N. (Alex), Fava, C. (Cristiano), Chambers, J.C. (John), Fox, E.R. (Ervin), Kumari, M. (Meena), Jin Go, M. (Min), Harst, P. (Pim) van der, Kao, W.-H.L. (Wen-Hong Linda), Sjögren, M. (Marketa), Vinay, D.G., Alexander, M. (Myriam), Tabara, Y. (Yasuharu), Shaw-Hawkins, S. (Sue), Whincup, P.H. (Peter), Liu, Y. (YongMei), Shi, G. (Gang), Kuusisto, J. (Johanna), Tayo, B. (Bamidele), Seielstad, M. (Mark), Sim, X. (Xueling), Hoang Nguyen, K.-D., Lehtimäki, T. (Terho), Matullo, G. (Giuseppe), Wu, Y. (Ying), Gaunt, T.R. (Tom), Onland-Moret, N.C. (Charlotte), Cooper, M.N. (Matthew), Platou, C. (Carl), Org, E. (Elin), Hardy, R. (Rebecca), Dahgam, S. (Santosh), Palmen, J. (Jutta), Vitart, V. (Veronique), Braund, P.S. (Peter), Kuznetsova, T. (Tatiana), Uiterwaal, C.S.P.M. (Cuno), Adeyemo, A. (Adebowale), Palmas, W. (Walter), Campbell, H. (Harry), Ludwig, B. (Barbara), Tomaszewski, M., Tzoulaki, I., Palmer, N.D. (Nicholette), Aspelund, T. (Thor), Garcia, M. (Melissa), Chang, Y.-P.C. (Yen-Pei), O´Connell, J.R., Steinle, N.I. (Nanette), Grobbee, D.E. (Diederick), Arking, D.E. (Dan), Kardia, S.L. (Sharon), Morrison, A.C. (Alanna), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), McArdle, W.L. (Wendy), Hadley, D. (David), Brown, M.J. (Morris), Connell, J. (John), Hingorani, A. (Aroon), Day, I.N.M. (Ian), Lawlor, D.A. (Debbie), Beilby, J.P. (John), Lawrence, R.W. (Robert), Clarke, R., Hopewell, J., Ongen, H. (Halit), Dreisbach, A.W. (Albert), Li, Y. (Yali), Hunter Young, J., Bis, J.C. (Joshua), Kähönen, M. (Mika), Viikari, J. (Jorma), Lee, N.R. (Nanette), Chen, M-H. (Ming-Huei), Olden, M. (Matthias), Pattaro, C. (Cristian), Hoffman Bolton, J.A. (Judith), Köttgen, A. (Anna), Bergmann, S.M. (Sven), Mooser, V. (Vincent), Chaturvedi, N. (Nish), Frayling, T.M. (Timothy), Islam, M. (Muhammad), Jafar, T.H. (Tazeen), Kulkarni, S.R. (Smita), Bornstein, S.R. (Stefan), Gräßler, J. (Jürgen), Groop, L. (Leif), Voight, B.F. (Benjamin), Kettunen, J. (Johannes), Howard, P. (Philip), Taylor, A. (Andrew), Guarrera, S. (Simonetta), Ricceri, F. (Fulvio), Emilsson, V. (Valur), Plump, A.S. (Andrew), Khaw, K-T. (Kay-Tee), Weder, A.B. (Alan), Hunt, S.C. (Steven), Sun, Y.V. (Yan), Bergman, R.N. (Richard), Collins, F.S. (Francis), Bonnycastle, L.L. (Lori), Scott, L.J. (Laura), Stringham, H.M. (Heather), Peltonen, L. (Leena Johanna), Perola, M. (Markus), Vartiainen, E. (Erkki), Brand, S.-M., Staessen, J.A. (Jan), Wang, Y.A. (Ying), Burton, P.R. (Paul), Soler Artigas, M. (Maria), Dong, Y. (Yanbin), Snieder, H. (Harold), Zhu, H. (Haidong), Lohman, K. (Kurt), Rudock, M.E. (Megan), Heckbert, S.R. (Susan), Wiggins, K.L. (Kerri), Doumatey, A. (Ayo), Shriner, D. (Daniel), Veldre, G. (Gudrun), Viigimaa, M. (Margus), Kinra, S. (Sanjay), Prabhakaran, D. (Dorairaj), Tripathy, V. (Vikal), Langefeld, C.D. (Carl), Rosengren, A. (Annika), Thelle, D.S. (Dag), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Forrester, T. (Terrence), Hilton, G. (Gina), McKenzie, C.A. (Colin), Salako, T. (Tunde), Iwai, N. (Naoharu), Kita, Y. (Yoshikuni), Ogihara, T. (Toshio), Ohkubo, T. (Takayoshi), Okamura, T. (Tomonori), Ueshima, H. (Hirotsugu), Umemura, S. (Satoshi), Eyheramendy, S. (Susana), Meitinger, T. (Thomas), Wichmann, H.E. (Heinz Erich), Shin Cho, Y. (Yoon), Kim, H.-L., Sehmi, J.S. (Joban), Hedblad, B. (Bo), Nilsson, P. (Peter), Davey-Smith, G. (George), Wong, A. (Andrew), Narisu, N. (Narisu), Stancáková, A. (Alena), Raffel, L.J. (Leslie), Yao, J. (Jie), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Shrine, N.R.G. (Nick), Wain, L.V. (Louise), Morken, M.A. (Mario), Swift, A.J. (Amy), Laitinen, J. (Jaana), Prokopenko, I. (Inga), Zitting, P. (Paavo), Humphries, S.E. (Steve), Danesh, J. (John), Rasheed, A. (Asif), Goel, A. (Anuj), Hamsten, A. (Anders), Watkins, H. (Hugh), Gilst, W.H. (Wiek) van, Janipalli, C.S. (Charles), Radha Mani, K., Yajnik, C. (Chittaranjan), Hofman, A. (Albert), Mattace Raso, F.U.S. (Francesco), Oostra, B.A. (Ben), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Rivadeneira Ramirez, F. (Fernando), Lakatta, E. (Edward), Orrù, M. (Marco), Scuteri, A. (Angelo), Ala-Korpela, M. (Mika), Kangas, A.J. (Antti), Lyytikäinen, L.-P. (Leo-Pekka), Soininen, P. (Pasi), Tukiainen, T. (Taru), Würtz, P. (Peter), Twee-Hee Ong, R. (Rick), Dörr, M. (Marcus), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Zelenika, D. (Diana), Deloukas, P. (Panagiotis), Mangino, M. (Massimo), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meschia, J.F. (James F.), Nalls, M.A. (Michael), Sharma, P. (Pankaj), Terzic, J. (Janos), Kranthi Kumar, M.V., Denniff, M. (Matthew), Zukowska-Szczechowska, E. (Ewa), Wagenknecht, L.E. (Lynne), Fowkes, F.G.R. (Gerald), Charchar, F.J. (Fadi), Schwarz, P.E.H. (Peter), Hayward, C. (Caroline), Guo, X. (Xiuqing), Rotimi, C. (Charles), Bots, M.L. (Michiel), Samani, N.J. (Nilesh), Polasek, O. (Ozren), Talmud, P.J. (Philippa), Nyberg, F. (Fredrik), Kuh, D. (Diana), Laan, M. (Maris), Hveem, K. (Kristian), Schouw, Y.T. (Yvonne) van der, Casas, J.P. (Juan), Mohlke, K.L. (Karen), Vineis, P. (Paolo), Raitakari, O. (Olli), Ganesh, S.K. (Santhi), Shyong Tai, E., Laakso, M. (Markku), Rao, D.C. (Dabeeru C.), Harris, T.B. (Tamara), Morris, R.W. (Richard), Dominiczak, A. (Anna), Kivimaki, M. (Mika), Marmot, M. (Michael), Miki, T. (Tetsuro), Saleheen, D., Chandak, G.R. (Giriraj), Coresh, J. (Josef), Navis, G. (Gerjan), Salomaa, V. (Veikko), Han, B.-G., Kooner, J.S. (Jaspal), Melander, O. (Olle), Ridker, P.M. (Paul), Bandinelli, S. (Stefania), Gyllensten, U. (Ulf), Wright, A.F. (Alan), Wilson, J.F. (James), Ferrucci, L. (Luigi), Farrall, M. (Martin), Tuomilehto, J. (Jaakko), Pramstaller, P.P. (Peter Paul), Elosua, R. (Roberto), Soranzo, N. (Nicole), Sijbrands, E.J.G. (Eric), Altshuler, D. (David), Loos, R.J.F. (Ruth), Shuldiner, A.R. (Alan), Gieger, C. (Christian), Meneton, P. (Pierre), Uitterlinden, A.G. (André), Wareham, N.J. (Nick), Gudnason, V. (Vilmundur), Rotter, J.I. (Jerome), Rettig, R. (Rainer), Uda, M. (Manuela), Strachan, D.P. (David), Witteman, J.C.M. (Jacqueline), Hartikainen, A.L., Beckmann, J.S. (Jacques), Boerwinkle, E.A. (Eric), Erdmann, J. (Jeanette), Vasan, R.S. (Ramachandran Srini), Boehnke, M. (Michael), Larson, M.G. (Martin), Järvelin, M.R., Psaty, B.M. (Bruce), Tikka-Kleemola, P. (Päivi), Newton-Cheh, C. (Christopher), Elliott, P. (Paul), Levy, D. (Daniel), Caulfield, M. (Mark), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda), Bakker, S.J.L. (Stephan), and Barroso, I.E. (Inês)
Abstract: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 geno
Published: 2011
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23. APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema

Author: Burkart, K. M., primary, Manichaikul, A., additional, Wilk, J. B., additional, Ahmed, F. S., additional, Burke, G. L., additional, Enright, P., additional, Hansel, N. N., additional, Haynes, D., additional, Heckbert, S. R., additional, Hoffman, E. A., additional, Kaufman, J. D., additional, Kurai, J., additional, Loehr, L., additional, London, S. J., additional, Meng, Y., additional, O'Connor, G. T., additional, Oelsner, E., additional, Petrini, M., additional, Pottinger, T. D., additional, Powell, C. A., additional, Redline, S., additional, Rotter, J. I., additional, Smith, L. J., additional, Soler Artigas, M., additional, Tobin, M. D., additional, Tsai, M. Y., additional, Watson, K., additional, White, W., additional, Young, T. R., additional, Rich, S. S., additional, and Barr, R. G., additional
Published: 2013
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24. Joint Effect of Single-Nucleotide Polymorphisms and Smoking Exposure in Chronic Obstructive Pulmonary Disease Risk

Author: Soler Artigas, M., primary, Wain, L. V., additional, Tobin, M. D., additional, and Hall, I. P., additional
Published: 2012
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25. Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Author: Soler Artigas M, Dw, Loth, Lv, Wain, Sa, Gharib, Obeidat M, Tang W, Zhai G, Jh, Zhao, Av, Smith, Je, Huffman, Albrecht E, Cm, Jackson, Dm, Evans, Cadby G, and Md, Tobin

26. Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function

Author: Tang W, Kowgier M, Dw, Loth, Soler Artigas M, Br, Joubert, Hodge E, Sa, Gharib, Av, Smith, Ruczinski I, Gudnason V, Ra, Mathias, Tb, Harris, Nn, Hansel, and Pa, Cassano

27. Genome-wide association study to identify genetic determinants of severe asthma

Author: Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, Hall, Ian P., Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, and Hall, Ian P.
Abstract: Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify common genetic variants affecting susceptibility to severe asthma. Methods A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10(−8) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10(−8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
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28. Genome-wide association study to identify genetic determinants of severe asthma

Author: Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, Hall, Ian P., Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, and Hall, Ian P.
Abstract: Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify common genetic variants affecting susceptibility to severe asthma. Methods A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10(−8) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10(−8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
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29. Genome-wide association study to identify genetic determinants of severe asthma

Author: Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, Hall, Ian P., Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, and Hall, Ian P.
Abstract: Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify common genetic variants affecting susceptibility to severe asthma. Methods A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10(−8) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10(−8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
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30. Genome-wide association study to identify genetic determinants of severe asthma

Author: Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, Hall, Ian P., Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, and Hall, Ian P.
Abstract: Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify common genetic variants affecting susceptibility to severe asthma. Methods A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10(−8) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10(−8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
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31. Genome-wide association study to identify genetic determinants of severe asthma

Author: Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, Hall, Ian P., Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, and Hall, Ian P.
Abstract: Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify common genetic variants affecting susceptibility to severe asthma. Methods A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10(−8) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10(−8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
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32. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. Casas, Moser, Jennifer, Whitbourne, Stacey B., Brewer, Jessica V., Aslan, Mihaela, Connor, Todd, Argyres, Dean P., Stephens, Brady, Brophy, Mary T., Humphries, Donald E., Selva, Luis E., Do, Nhan, Shayan, Shahpoor, Cho, Kelly, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Mattocks, Kristin, Harley, John, Zablocki, Clement J., Whittle, Jeffrey, Jacono, Frank, Gutierrez, Salvador, Gibson, Gretchen, Hammer, Kimberly, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Mathew, Roy, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Ivins, Douglas, Mastorides, Stephen, Moorman, Jonathan, Gappy, Saib, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Okusaga, Olaoluwa, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Tandon, Neeraj, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Liangpunsakul, Suthat, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Constans, Joseph, Meyer, Paul, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Gaddy, Melinda, Wallbom, Agnes, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Ross, George, Tsao, Philip, Strollo, Patrick, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Huq, Mostaqul, Fayad, Joseph, Hung, Adriana, Lichy, Jack, Hurley, Robin, Robey, Brooks, Striker, Robert, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Penninx, Brenda W. J. H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., O'Connell, Kevin S., Coombes, Brandon, Qiao, Zhen, Als, Thomas D., Børte, Sigrid, Charney, Alexander W., Drange, Ole Kristian, Gandal, Michael J., Hagenaars, Saskia P., Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M., Sloofman, Laura G., Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Gizer, Ian R., Gordon-Smith, Katherine, Greenwood, Tiffany A., Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Kogevinas, Manolis, Koromina, Maria, Kranz, Thorsten M., Kranzler, Henry R., Kubo, Michiaki, Kupka, Ralph, Kushner, Steven A., Lavebratt, Catharina, Lawrence, Jacob, Leber, Markus, Lee, Heon-Jeong, Lee, Phil H., Levy, Shawn E., Lewis, Catrin, Liao, Calwing, Lundberg, Martin, Magnusson, Sigurdur H., Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, McGregor, Nathaniel W., McKay, James D., Medeiros, Helena, Millischer, Vincent, Moran, Jennifer L., Morris, Derek W., Mühleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Olde Loohuis, Loes M., Oruc, Lilijana, Papiol, Sergi, Pardiñas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Quested, Digby, Raj, Towfique, Rapaport, Mark H., Regeer, Eline J., Rivas, Fabio, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Xi, Simon, Xu, Wei, Kay Yang, Jessica Mei, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dikeos, Dimitris, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Mitchell, Philip B., Morken, Gunnar, Mowry, Bryan, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Oedegaard, Ketil J., Olsson, Tomas, Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Stordal, Eystein, Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Adan, Roger A. H., Ando, Tetsuya, Aschauer, Harald, Baker, Jessica H., Bencko, Vladimir, Bergen, Andrew W., Birgegård, Andreas, Boden, Joseph M., Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Brandt, Harry, Buehren, Katharina, Bulik, Cynthia M., Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S. P., de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dina, Christian, Dmitrzak-Weglarz, Monika, Martinez, Elisa Docampo, Duncan, Laramie E., Egberts, Karin, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Munn-Chernoff, Melissa A., Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, Olsen, Catherine M., O'Toole, Julie K., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pearson, John F., Ehrlich, Stefan, Escaramís, Geòrgia, Espeseth, Thomas, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Floyd, James A. B., Föcker, Manuel, Foretova, Lenka, Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Gambaro, Giovanni, Giegling, Ina, Giuranna, Johanna, Giusti-Rodríquez, Paola, Gonidakis, Fragiskos, Gordon, Scott, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A., Hanscombe, Ken B., Hatzikotoulas, Konstantinos, Hebebrand, Johannes, Helder, Sietske G., Henders, Anjali K., Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Horwood, L. John, Hübel, Christopher, Petersen, Liselotte V., Pinto, Dalila, Purves, Kirstin L., Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W., Schmidt, Ulrike, Schork, Nicholas J., Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op 't Landt, Margarita C. T., Slopien, Agnieszka, Soranzo, Nicole, Sorbi, Sandro, Southam, Lorraine, Steen, Vidar W., Strober, Michael, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Kaplan, Allan S., Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J. H., Kaye, Walter H., Kennedy, Martin A., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Kirk, Katherine M., Klareskog, Lars, Klump, Kelly L., Knudsen, Gun Peggy S., Larsen, Janne T., Le Hellard, Stephanie, Leppä, Virpi M., Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lin, Bochao Danae, Lundervold, Astri, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Stuber, Garret D., Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Thornton, Laura M., Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wade, Tracey D., Wagner, Gudrun, Walton, Esther, Watson, Hunna J., Whiteman, David C., Wichmann, H. Erich, Widen, Elisabeth, Woodside, D. Blake, Yao, Shuyang, Yilmaz, Zeynep, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Jungkunz, Martin, Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., Levey, D. F., Lori, A., Shabalin, A., Starnawska, A., Su, M. -H., Watson, H. J., Adams, M., Awasthi, S., Gandal, M., Hafferty, J. D., Hishimoto, A., Kim, M., Okazaki, S., Otsuka, I., Ripke, S., Ware, E. B., Bergen, A. W., Berrettini, W. H., Bohus, M., Brandt, H., Chang, X., Chen, W. J., Chen, H. -C., Crawford, S., Crow, S., Diblasi, E., Duriez, P., Fernandez-Aranda, F., Fichter, M. M., Gallinger, S., Glatt, S. J., Gorwood, P., Guo, Y., Hakonarson, H., Halmi, K. A., Hwu, H. -G., Jain, S., Jamain, S., Jimenez-Murcia, S., Johnson, C., Kaplan, A. S., Kaye, W. H., Keel, P. K., Kennedy, J. L., Klump, K. L., Li, D., Liao, S. -C., Lieb, K., Lilenfeld, L., Liu, C. -M., Magistretti, P. J., Marshall, C. R., Mitchell, J. E., Monson, E. T., Myers, R. M., Pinto, D., Powers, A., Ramoz, N., Roepke, S., Rozanov, V., Scherer, S. W., Schmahl, C., Sokolowski, M., Strober, M., Thornton, L. M., Treasure, J., Tsuang, M. T., Witt, S. H., Woodside, D. B., Yilmaz, Z., Zillich, L., Adolfsson, R., Agartz, I., Air, T. M., Alda, M., Alfredsson, L., Andreassen, O. A., Anjorin, A., Appadurai, V., Soler Artigas, M., Van der Auwera, S., Azevedo, M. H., Bass, N., Bau, C. H. D., Baune, B. T., Bellivier, F., Berger, K., Biernacka, J. M., Bigdeli, T. B., Binder, E. B., Boehnke, M., Boks, M. P., Bosch, R., Braff, D. L., Bryant, R., Budde, M., Byrne, E. M., Cahn, W., Casas, M., Castelao, E., Cervilla, J. A., Chaumette, B., Cichon, S., Corvin, A., Craddock, N., Craig, D., Degenhardt, F., Djurovic, S., Edenberg, H. J., Fanous, A. H., Foo, J. C., Forstner, A. J., Frye, M., Fullerton, J. M., Gatt, J. M., Gejman, P. V., Giegling, I., Grabe, H. J., Green, M. J., Grevet, E. H., Grigoroiu-Serbanescu, M., Gutierrez, B., Guzman-Parra, J., Hamilton, S. P., Hamshere, M. L., Hartmann, A., Hauser, J., Heilmann-Heimbach, S., Hoffmann, P., Ising, M., Jones, I., Jones, L. A., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kendler, K. S., Kloiber, S., Koenen, K. C., Kogevinas, M., Konte, B., Krebs, M. -O., Landen, M., Lawrence, J., Leboyer, M., Lee, P. H., Levinson, D. F., Liao, C., Lissowska, J., Lucae, S., Mayoral, F., Mcelroy, S. L., Mcgrath, P., Mcguffin, P., Mcquillin, A., Medland, S. E., Mehta, D., Melle, I., Milaneschi, Y., Mitchell, P. B., Molina, E., Morken, G., Mortensen, P. B., Muller-Myhsok, B., Nievergelt, C., Nimgaonkar, V., Nothen, M. M., O'Donovan, M. C., Ophoff, R. A., Owen, M. J., Pato, C., Pato, M. T., Penninx, B. W. J. H., Pimm, J., Pistis, G., Potash, J. B., Power, R. A., Preisig, M., Quested, D., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Richarte, V., Rietschel, M., Rivera, M., Roberts, A., Roberts, G., Rouleau, G. A., Rovaris, D. L., Rujescu, D., Sanchez-Mora, C., Sanders, A. R., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Shi, J., Shyn, S. I., Sirignano, L., Sklar, P., Smeland, O. B., Smoller, J. W., Sonuga-Barke, E. J. S., Spalletta, G., Strauss, J. S., Swiatkowska, B., Trzaskowski, M., Turecki, G., Vilar-Ribo, L., Vincent, J. B., Volzke, H., Walters, J. T. R., Shannon Weickert, C., Weickert, T. W., Weissman, M. M., Williams, L. M., Wray, N. R., Zai, C. C., Ashley-Koch, A. E., Beckham, J. C., Hauser, E. R., Hauser, M. A., Kimbrel, N. A., Lindquist, J. H., Mcmahon, B., Oslin, D. W., Qin, X., Mattheisen, M., Abdellaoui, A., Adams, M. J., Agerbo, E., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Christensen, J. H., Clarke, T. -K., Colodro-Conde, L., Couvy-Duchesne, B., Crawford, G. E., Davies, G., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Hassan Kiadeh, F. F., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Goes, F. S., Gordon, S. D., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Boomsma, D. I., Dannlowski, U., Depaulo, J. R., Domenici, E., Domschke, K., Esko, T., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Herms, S., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Howard, D. M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Middeldorp, C. M., Mihailov, E., Milani, L., Mondimore, F. M., Montgomery, G. W., Mostafavi, S., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Hayward, C., Heath, A. C., Lewis, G., Li, Q. S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Nordentoft, M., Paciga, S. A., Pedersen, N. L., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Peyrot, W. J., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Mirza, S. S., Schoevers, R., Schulte, E. C., Shen, L., Sigurdsson, E., Sinnamon, G. C. B., Smit, J. H., Smith, D. J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K. E., Teismann, H., Teumer, A., Thompson, W., Thomson, P. A., Thorgeirsson, T. E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A. G., Umbricht, D., der Auwera, S. V., van Hemert, A. M., Viktorin, A., Visscher, P. M., Wang, Y., Webb, B. T., Perlis, R. H., Porteous, D. J., Schaefer, C., Stefansson, K., Tiemeier, H., Uher, R., Werge, T., Lewis, C. M., Breen, G., Borglum, A. D., Sullivan, P. F., O'Connell, K. S., Coombes, B., Qiao, Z., Als, T. D., Borte, S., Charney, A. W., Drange, O. K., Gandal, M. J., Hagenaars, S. P., Ikeda, M., Kamitaki, N., Krebs, K., Panagiotaropoulou, G., Schilder, B. M., Sloofman, L. G., Winsvold, B. S., Won, H. -H., Abramova, L., Adorjan, K., Al Eissa, M., Albani, D., Alliey-Rodriguez, N., Antilla, V., Antoniou, A., Baek, J. H., Bauer, M., Beins, E. C., Bergen, S. 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A., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K. M., Klareskog, L., Knudsen, G. P. S., Larsen, J. T., Le Hellard, S., Leppa, V. M., Lichtenstein, P., Lin, B. D., Lundervold, A., Luykx, J., Maj, M., Mannik, K., Marsal, S., Stuber, G. D., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wade, T. D., Wagner, G., Walton, E., Whiteman, D. C., Wichmann, H. E., Widen, E., Yao, S., Zeggini, E., Zerwas, S., Zipfel, S., Jungkunz, M., Dietl, L., Schwarze, C. E., Dahmen, N., Schott, B. H., Mobascher, A., Crivelli, S., Dennis, M. F., Harvey, P. D., Carter, B. W., Huffman, J. E., Jacobson, D., Madduri, R., Olsen, M. K., Pestian, J., Gaziano, J. M., Muralidhar, S., Ramoni, R., Beckham, J., Chang, K. -M., O'Donnell, C. J., Tsao, P. S., Breeling, J., Huang, G., Romero, J. P. C., Moser, J., Whitbourne, S. B., Brewer, J. V., Aslan, M., Connor, T., Argyres, D. P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards A.C., Galfalvy H., Levey D.F., Lori A., Shabalin A., Starnawska A., Su M.-H., Watson H.J., Adams M., Awasthi S., Gandal M., Hafferty J.D., Hishimoto A., Kim M., Okazaki S., Otsuka I., Ripke S., Ware E.B., Bergen A.W., Berrettini W.H., Bohus M., Brandt H., Chang X., Chen W.J., Chen H.-C., Crawford S., Crow S., DiBlasi E., Duriez P., Fernandez-Aranda F., Fichter M.M., Gallinger S., Glatt S.J., Gorwood P., Guo Y., Hakonarson H., Halmi K.A., Hwu H.-G., Jain S., Jamain S., Jimenez-Murcia S., Johnson C., Kaplan A.S., Kaye W.H., Keel P.K., Kennedy J.L., Klump K.L., Li D., Liao S.-C., Lieb K., Lilenfeld L., Liu C.-M., Magistretti P.J., Marshall C.R., Mitchell J.E., Monson E.T., Myers R.M., Pinto D., Powers A., Ramoz N., Roepke S., Rozanov V., Scherer S.W., Schmahl C., Sokolowski M., Strober M., Thornton L.M., Treasure J., Tsuang M.T., Witt S.H., Woodside D.B., Yilmaz Z., Zillich L., Adolfsson R., Agartz I., Air T.M., Alda M., Alfredsson L., Andreassen O.A., Anjorin A., Appadurai V., Soler 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F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.
Subjects: LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract: Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
Published: 2022
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33. Gut microbiota signature in treatment-naïve attention-deficit/hyperactivity disorder

Author: Marta Ribasés, Christian Fadeuilhe, Josep Antoni Ramos-Quiroga, Lorena Arribas, Montserrat Corrales, Alejandro Arias-Vasquez, Cristina Sánchez-Mora, Silvia Karina Rosales-Ortiz, María Soler-Artigas, Vanesa Richarte, Estela Camus Garcia, Laura Vilar-Ribó, Institut Català de la Salut, [Richarte V, Corrales M, Fadeuilhe C] Grup de Recerca en Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. Departament de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Sánchez-Mora C, Vilar-Ribó L] Grup de Recerca en Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. Unitat de Genètica Psiquiàtrica, Grup de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Arribas L] Grup de Recerca en Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Unitat de Genètica Psiquiàtrica, Grup de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Garcia E] Unitat de Genètica Psiquiàtrica, Grup de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Rosales-Ortiz SK] Unitat de Genètica Psiquiàtrica, Grup de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Department of Biomedicine, University of Barcelona, Barcelona, Spain. [Soler-Artigas M, Ribasés M] Grup de Recerca en Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. Unitat de Genètica Psiquiàtrica, Grup de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Department of Genetics, Microbiology & Statistics, University of Barcelona, Barcelona, Spain. [Ramos-Quiroga JA] Grup de Recerca en Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. Departament de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat de Genètica Psiquiàtrica, Grup de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Adult, 0301 basic medicine, fenómenos microbiológicos::microbiota::microbiota intestinal [FENÓMENOS Y PROCESOS], Scientific community, Adolescent, Veillonellaceae, Physiology, Neurosciences. Biological psychiatry. Neuropsychiatry, Gut flora, Article, Body Mass Index, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Mental Disorders::Neurodevelopmental Disorders::Attention Deficit and Disruptive Behavior Disorders::Attention Deficit Disorder with Hyperactivity [PSYCHIATRY AND PSYCHOLOGY], Abundance (ecology), mental disorders, medicine, Humans, ADHD, Attention deficit hyperactivity disorder, Attention, Intestins - Microbiologia, Child, Relative species abundance, Biological Psychiatry, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Microbiological Phenomena::Microbiota::Gastrointestinal Microbiome [PHENOMENA AND PROCESSES], biology, Gastrointestinal Microbiome, medicine.disease, biology.organism_classification, 3. Good health, Psychiatry and Mental health, 030104 developmental biology, Trastorn per dèficit d'atenció amb hiperactivitat, Attention Deficit Disorder with Hyperactivity, Neurodevelopmental Disorders, Dialister, trastornos mentales::trastornos del desarrollo neurológico::trastornos conductuales disruptivos y déficit de atención::trastornos de déficit de atención con hiperactividad [PSIQUIATRÍA Y PSICOLOGÍA], Body mass index, 030217 neurology & neurosurgery, RC321-571
Abstract: Compelling evidence supports alterations in gut microbial diversity, bacterial composition, and/or relative abundance of several bacterial taxa in attention-deficit/hyperactivity disorder (ADHD). However, findings for ADHD are inconsistent among studies, and specific gut microbiome signatures for the disorder remain unknown. Given that previous studies have mainly focused on the pediatric form of the disorder and involved small sample sizes, we conducted the largest study to date to compare the gastrointestinal microbiome composition in 100 medication-naïve adults with ADHD and 100 sex-matched healthy controls. We found evidence that ADHD subjects have differences in the relative abundance of several microbial taxa. At the family level, our data support a lower relative abundance of Gracilibacteraceae and higher levels of Selenomonadaceae and Veillonellaceae in adults with ADHD. In addition, the ADHD group showed higher levels of Dialister and Megamonas and lower abundance of Anaerotaenia and Gracilibacter at the genus level. All four selected genera explained 15% of the variance of ADHD, and this microbial signature achieved an overall sensitivity of 74% and a specificity of 71% for distinguishing between ADHD patients and healthy controls. We also tested whether the selected genera correlate with age, body mass index (BMI), or scores of the ADHD rating scale but found no evidence of correlation between genera relative abundance and any of the selected traits. These results are in line with recent studies supporting gut microbiome alterations in neurodevelopment disorders, but further studies are needed to elucidate the role of the gut microbiota on the ADHD across the lifespan and its contribution to the persistence of the disorder from childhood to adulthood.
Published: 2021

34. Genetic association study of childhood aggression across raters, instruments, and age

Author: Nicholas G. Martin, S. Alexandra Burt, Louise Arseneault, Fazil Aliev, Luke M. Evans, Hill F. Ip, Beate St Pourcain, Michel G. Nivard, William E. Copeland, Rebecca K. Vinding, Scott Gordon, Koen Bolhuis, Christian J. Hopfer, Gun Peggy Knudsen, Stefan Johansson, Avshalom Caspi, Richard Border, Chandra A. Reynolds, Pål R. Njølstad, Liisa Keltikangas-Järvinen, Dorret I. Boomsma, Klaus Bønnelykke, Teemu Palviainen, Marta Ribasés, Alina Rodriguez, Catharina A. Hartman, Ilkka Seppälä, Christel M. Middeldorp, Rosa Bosch, Jan Haavik, Gail M. Williams, Andrea G. Allegrini, Ruth Ks, John R. B. Perry, Hadi Zafarmand, Chang Jiang, Elizabeth J. Costello, Camiel M. van der Laan, Olli T. Raitakari, Miquel Casas, Isabell Brikell, William G. Iacono, Jaakko Kaprio, John K. Hewitt, Andrew C. Heath, Eero Vuoksimaa, Xiaoran Tong, Gemma Español, Erik A. Ehli, Richie Poulton, Gareth E. Davies, Albertine J. Oldehinkel, Hans Bisgaard, Naomi R. Wray, Ted Reichborn-Kjennerud, Robert Plomin, Michael C. Stallings, Qing Lu, Jackob M. Najman, Daniel E. Adkins, Yi Lu, Harold Snieder, Sally J. Wadsworth, Alexander Neumann, Alexandra Havdahl, Karen Sugden, Kelly L. Klump, Andrew Smolen, Henrik Larsson, Toos C. E. M. van Beijsterveldt, Kenneth Krauter, Tarunveer S. Ahluwalia, Tellervo Korhonen, Andrey A. Shabalin, Joachim Heinrich, Anke R. Hammerschlag, Shelby Marrington, Lærke Sass, Pamela A. F. Madden, Henning Tiemeier, Tanja Vrijkotte, Paul Lichtenstein, Terho Lehtimäki, Ville Karhunen, Cristina Sánchez-Mora, Robin P. Corley, Anna A. E. Vinkhuyzen, Richard J. Rose, Per Magnus, Sabrina Llop, Ilja M. Nolte, S.A. Brown, Christian Hakulinen, Anjali K. Henders, Marie Standl, Silvia Alemany, Gretchen R.B. Saunders, Jouke-Jan Hottenga, Eveline L. de Zeeuw, Meike Bartels, Elisabeth Thiering, José J. Morosoli, Fiona A. Hagenbeek, Laura Pulkki-Råback, Frank C. Verhulst, Martin A. Kennedy, Craig E. Pennell, Eva Krapohl, Kaili Rimfeld, Tetyana Zayats, Lucía Colodro-Conde, Judith B.M. Ensink, André G. Uitterlinden, Natalia Vilor-Tejedor, Felix R. Day, Jennifer R. Harris, George Davey Smith, Qi Chen, Sebastian Lundström, Marjo-Riitta Järvelin, Alyce M. Whipp, Katrina L. Grasby, L. John Horwood, John Pearson, Judy L. Silberg, Paula Rovira, Hermine H. Maes, Carol A. Wang, Roseann E. Peterson, Tamara L. Wall, Andrew J. O. Whitehouse, Maria-Jose Lopez-Espinosa, Najaf Amin, Jess Tyrrell, Danielle M. Dick, Sarah E. Medland, Allison L. Miller, Øyvind Helgeland, Josep Antoni Ramos Quiroga, Joseph M. Boden, Abdullah Mamun, James Scott, María Soler Artigas, Joseph A. Prinz, Lindon J. Eaves, Terrie E. Moffitt, Matt McGue, Jordi Sunyer, Joanna Martin, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Apollo-University Of Cambridge Repository, Ip, Hill F [0000-0003-1991-5019], Sánchez-Mora, Cristina [0000-0003-4211-1107], Nolte, Ilja M [0000-0001-5047-4077], St Pourcain, Beate [0000-0002-4680-3517], Palviainen, Teemu [0000-0002-7847-8384], Colodro-Conde, Lucía [0000-0002-9004-364X], Gordon, Scott [0000-0001-7623-328X], Aliev, Fazil [0000-0001-8357-4699], Karhunen, Ville [0000-0001-6064-1588], Border, Richard [0000-0002-6293-2968], Ahluwalia, Tarunveer S [0000-0002-7464-3354], Day, Felix R [0000-0003-3789-7651], Hottenga, Jouke-Jan [0000-0002-5668-2368], Rimfeld, Kaili [0000-0001-5139-065X], Lu, Yi [0000-0001-9933-3654], Soler Artigas, María [0000-0002-3213-1107], Bosch, Rosa [0000-0002-7596-183X], Ramos Quiroga, Josep Antoni [0000-0003-1622-0350], Neumann, Alexander [0000-0001-6653-3203], Grasby, Katrina [0000-0001-8539-0228], Middeldorp, Christel [0000-0002-6218-0428], Evans, Luke M [0000-0002-7458-1720], Alemany, Silvia [0000-0002-7925-6767], Sass, Lærke [0000-0002-5217-7014], Ruth, Kate [0000-0003-4966-9170], Ehli, Erik A [0000-0002-7865-3015], Hagenbeek, Fiona A [0000-0002-8773-0430], Snieder, Harold [0000-0003-1949-2298], Uitterlinden, André G [0000-0002-7276-3387], Haavik, Jan [0000-0001-7865-2808], Johansson, Stefan [0000-0002-2298-7008], Knudsen, Gun Peggy S [0000-0002-6193-4291], Njolstad, Pal Rasmus [0000-0003-0304-6728], Rodriguez, Alina [0000-0003-1209-8802], Brown, Sandy [0000-0001-8780-0323], Miller, Allison [0000-0003-3816-2251], Keltikangas-Järvinen, Liisa [0000-0002-7977-3852], Havdahl, Alexandra [0000-0002-9268-0423], Perry, John RB [0000-0001-6483-3771], Lehtimäki, Terho [0000-0002-2555-4427], Arseneault, Louise [0000-0002-2938-2191], Boden, Joseph [0000-0003-1502-1608], Pearson, John [0000-0001-5607-4517], Kennedy, Martin [0000-0002-6445-8526], Poulton, Richie [0000-0002-1052-4583], Copeland, William E [0000-0002-1348-7781], Wray, Naomi [0000-0001-7421-3357], Järvelin, Marjo-Riitta [0000-0002-2149-0630], McGue, Matt [0000-0002-5580-1433], Pennell, Craig E [0000-0002-0937-6165], Dick, Danielle M [0000-0002-1636-893X], Martin, Nicholas G [0000-0003-4069-8020], Medland, Sarah E [0000-0003-1382-380X], Kaprio, Jaakko [0000-0002-3716-2455], Tiemeier, Henning [0000-0002-4395-1397], Davey Smith, George [0000-0002-1407-8314], Oldehinkel, Albertine J [0000-0003-3925-3913], Ribasés, Marta [0000-0003-1039-1116], Lichtenstein, Paul [0000-0003-3037-5287], Plomin, Robert [0000-0002-0756-3629], Bartels, Meike [0000-0002-9667-7555], Nivard, Michel G [0000-0003-2015-1888], Boomsma, Dorret I [0000-0002-7099-7972], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Child and Adolescent Psychiatry / Psychology, Epidemiology, Internal Medicine, Institute for Molecular Medicine Finland, Genetic Epidemiology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Tellervo Korhonen / Principal Investigator, Cognitive and Brain Aging, Faculty Common Matters (Faculty of Medicine), Medicum, Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Psychology and Logopedics, Helsinki Inequality Initiative (INEQ), Faculty Common Matters (Faculty of Education), Psychosocial factors and health, Behavioural Sciences, Department of Public Health, Adult Psychiatry, Epidemiology and Data Science, APH - Aging & Later Life, APH - Methodology, ARD - Amsterdam Reproduction and Development, Graduate School, Child Psychiatry, ACS - Pulmonary hypertension & thrombosis, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, Public and occupational health, APH - Health Behaviors & Chronic Diseases, Institut Català de la Salut, [Ip HF] Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. [van der Laan CM] Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Netherlands Institute for the Study of Crime and Law Enforcement, Amsterdam, The Netherlands. [Krapohl EML] Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK. [Brikell I] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Sánchez-Mora C, Soler Artigas M, Rovira P, Ribasés M] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. Unitat de Genètica Psiquiàtrica, Grup de Recerca en Psiquiatria, Salut Mental i Addicció, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Nolte IM] Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. [Bosch R] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. Servei de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Español G] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ramos Quiroga JA, Ribasés M] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain. Unitat de Genètica Psiquiàtrica, Grup de Recerca en Psiquiatria, Salut Mental i Addicció, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Biological Psychology, APH - Personalized Medicine, APH - Mental Health, Amsterdam Reproduction & Development, Perry, John R B [0000-0001-6483-3771], Ip, Hill F. [0000-0003-1991-5019], Nolte, Ilja M. [0000-0001-5047-4077], Ahluwalia, Tarunveer S. [0000-0002-7464-3354], Day, Felix R. [0000-0003-3789-7651], Evans, Luke M. [0000-0002-7458-1720], Ehli, Erik A. [0000-0002-7865-3015], Hagenbeek, Fiona A. [0000-0002-8773-0430], Uitterlinden, André G. [0000-0002-7276-3387], Knudsen, Gun Peggy S. [0000-0002-6193-4291], Perry, John R. B. [0000-0001-6483-3771], Copeland, William E. [0000-0002-1348-7781], Pennell, Craig E. [0000-0002-0937-6165], Dick, Danielle M. [0000-0002-1636-893X], Martin, Nicholas G. [0000-0003-4069-8020], Medland, Sarah E. [0000-0003-1382-380X], Oldehinkel, Albertine J. [0000-0003-3925-3913], Nivard, Michel G. [0000-0003-2015-1888], and Boomsma, Dorret I. [0000-0002-7099-7972]
Subjects: 0301 basic medicine, DISORDER, 45/43, Genome-wide association study, 3124 Neurology and psychiatry, 0302 clinical medicine, Child, Psychiatry, 0303 health sciences, trastornos mentales [PSIQUIATRÍA Y PSICOLOGÍA], HERITABILITY, Mental Disorders, Cognition, Genomics, Explained variation, Justice and Strong Institutions, Aggression, Psychiatry and Mental health, Meta-analysis, ADOLESCENCE, Child, Preschool, conducta y mecanismos de la conducta::conducta::síntomas conductuales::agresión [PSIQUIATRÍA Y PSICOLOGÍA], 631/208/212, Female, Biological psychiatry, medicine.symptom, Life Sciences & Biomedicine, Investigative Techniques::Genetic Techniques::Genetic Association Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], BEHAVIOR, RC321-571, Childhood aggression, Clinical psychology, SDG 16 - Peace, Adolescent, Mental Disorders [PSYCHIATRY AND PSYCHOLOGY], Neurosciences. Biological psychiatry. Neuropsychiatry, Single-nucleotide polymorphism, Biology, 3121 Internal medicine, Malalties mentals - Aspectes genètics, Genetic correlation, Article, 1117 Public Health and Health Services, Cellular and Molecular Neuroscience, 03 medical and health sciences, 631/477/2811, SDG 3 - Good Health and Well-being, Human behaviour, medicine, SNP, Humans, GENOME-WIDE ASSOCIATION, Biological Psychiatry, Genetic Association Studies, 030304 developmental biology, Genetic association, Retrospective Studies, técnicas de investigación::técnicas genéticas::estudios de asociación genética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Science & Technology, SDG 16 - Peace, Justice and Strong Institutions, Infant, Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Aggression [PSYCHIATRY AND PSYCHOLOGY], 1103 Clinical Sciences, Agressivitat en els infants, Heritability, 030104 developmental biology, 1701 Psychology, ORIGINS, Research Programm of Donders Centre for Neuroscience, 3111 Biomedicine, TRAJECTORIES, 030217 neurology & neurosurgery, Demography, Genome-Wide Association Study
Abstract: Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range $$\left| {r_g} \right|$$ r g : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range $$\left| {r_g} \right|$$ r g : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
Published: 2021
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35. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author: James McKay, Frank Bellivier, Mark A. Frye, Bertram Müller-Myhsok, Fermín Mayoral, I. Nicol Ferrier, Marion Leboyer, Fabian Streit, Dan J. Stein, James L. Kennedy, Christine Søholm Hansen, Scott D. Gordon, Beata Świątkowska, Valentina Escott-Price, Michael Bauer, Lina Martinsson, Donald J. MacIntyre, Oleksandr Frei, Daniel J. Smith, Sara A. Paciga, Takeo Saito, Jennifer L. Moran, Verneri Antilla, C Pantelis, Tomas Olsson, Swapnil Awasthi, Lena Backlund, Eirini Maratou, Martin Schalling, John B. Vincent, Niamh Mullins, Sarah E. Bergen, Niamh L. O'Brien, Marco P. Boks, Carsten Bøcker Pedersen, Mikael Landén, Franziska Degenhardt, Hang Zhou, Margarita Rivera, Andrew M. McIntosh, Manuel Mattheisen, Shawn Levy, Roy H. Perlis, John P. Rice, Sigurdur H. Magnusson, Amanda Dobbyn, Michael Conlon O'Donovan, Julien Bryois, Wolfgang Maier, John-Anker Zwart, J. Raymond DePaulo, Martin Alda, Laura G. Sloofman, Friederike Sophie David, James A. Knowles, Aiden Corvin, Thomas G. Schulze, Markus M. Nöthen, Nolan Kamitaki, Nina Dalkner, Brandon J. Coombes, Gustavo Turecki, Allan H. Young, Caroline M. Nievergelt, Patricia T. Michie, Ingrid Agartz, Towfique Raj, Diego Albani, Maria Grigoroiu-Serbanescu, Bernhard T. Baune, Kyooseob Ha, Vincent Millischer, Engilbert Sigurdsson, Eva C. Beins, Nicholas G. Martin, Gulja Babadjanova, Josef Frank, Eva Z. Reininghaus, Patrick F. Sullivan, Ian R. Gizer, Guy A. Rouleau, Carmel M. Loughland, Christine Lochner, Thorsten M. Kranz, Amy Perry, Arne E. Vaaler, Mariam M. Al Eissa, Simon Xi, Claire O'Donovan, Josep Antoni Ramos-Quiroga, Ketil J. Oedegaard, Helmut Vedder, Carol A. Mathews, Panagiotis Ferentinos, Tim B. Bigdeli, Derek W. Morris, Per Hoffmann, Mark Hyman Rapaport, Peter P. Zandi, Michael John Owen, Douglas M. Ruderfer, Anders D. Børglum, Catharina Lavebratt, Thorgeir E. Thorgeirsson, Paul A. Tooney, Michiaki Kubo, Steven A. Kushner, Jan Hillert, Loes M. Olde Loohuis, Anastasia Antoniou, Murielle Brum, Chikashi Terao, Nathaniel W. McGregor, Fabio Rivas, James B. Potash, Kevin S. O’Connell, Susanne Lucae, Brian M. Schilder, Katrin Gade, Stephan Ripke, Kristina Adorjan, Kari Stefansson, Tiffany A. Greenwood, Panos Roussos, Sarah Kittel-Schneider, Steven A. McCarroll, Sergi Papiol, Heon Jeong Lee, Assen Jablensky, Liliya Abramova, Dennis Hellgren, Jonas Bybjerg-Grauholm, Martin Lundberg, Hong-Hee Won, William Byerley, Lars Alfredsson, Joel Gelernter, Andrew McQuillin, Claire Slaney, Marta Ribasés, Stephanie H. Witt, Yoichiro Kamatani, Kyung Sue Hong, Marie Bækvad-Hansen, María Soler Artigas, Julie M. Cunningham, Fanny Senner, Stacy Steinberg, Paul D. Shilling, Nakao Iwata, Eystein Stordal, Armin Birner, Sarah E. Medland, Miquel Casas, Ben Michael Brumpton, Erlend Bøen, Bryan J. Mowry, Jolanta Lissowska, Francis J. McMahon, Howard J. Edenberg, Grant W. Montgomery, John I. Nurnberger, Stéphane Jamain, Claudio Toma, Ney Alliey-Rodriguez, Ole Mors, Micha Gawlik, David Curtis, Catrin Lewis, Evangelia-Eirini Tsermpini, Georgia Panagiotaropoulou, Marcella Rietschel, Jessica Yang, Ian Jones, Eduard Vieta, Ole A. Andreassen, Richard M. Myers, Dimitris Dikeos, Melissa J. Green, Janet L. Sobell, Maria Koromina, Piotr M. Czerski, Lilijana Oruc, Sven Cichon, Udo Dannlowski, Bruno Etain, Monika Budde, Alessia Fiorentino, Naomi R. Wray, Qingqin S. Li, Murray J. Cairns, Jonathan R. I. Coleman, Jose Guzman-Parra, Andreas J. Forstner, Hannah Young, Alfredo B. Cuellar-Barboza, Julian Roth, Torbjørn Elvsåshagen, Zhen Qiao, Thomas Werge, Athanassios Douzenis, Cristiana Cruceanu, Rolf Adolfsson, Peter Holmans, Vaughan J. Carr, Thomas W. Weickert, Masashi Ikeda, Joanna M. Biernacka, Lea Sirignano, Adam X. Maihofer, Ralph W. Kupka, John Strauss, Anders M. Dale, Elliot S. Gershon, Jakob Grove, Arianna Di Florio, Helena Medeiros, Ingrid Melle, Preben Bo Mortensen, Kristi Krebs, Saskia P. Hagenaars, Liz Forty, Stanley V. Catts, David M. Hougaard, Marianne Giørtz Pedersen, Andreas Reif, Toni-Kim Clarke, Anne T. Spijker, Danielle Posthuma, Manolis Kogevinas, Michael Boehnke, Rosa Bosch, Gerome Breen, Benjamin M. Neale, Jessica S. Johnson, Katherine Gordon-Smith, Cristina Sánchez-Mora, Alexander W. Charney, Henry R. Kranzler, Digby Quested, René S. Kahn, Lili Milani, Merete Nordentoft, Nathalie Brunkhorst-Kanaan, Laura M. Huckins, James T.R. Walters, Sigrid Børte, Antonio F. Pardiñas, Kristian Hveem, Julie Garnham, Jacob Lawrence, Vassily Trubetskoy, Rodney J. Scott, Nicholas Bass, Carlos N. Pato, Andrea Pfennig, Wei Xu, Calwing Liao, Nicholas John Craddock, Thomas Damm Als, Christina M. Hultman, Fernando S. Goes, Adebayo Anjorin, Evgenia Porichi, Frans Henskens, Nelson B. Freimer, Janice M. Fullerton, Cathryn M. Lewis, Srdjan Djurovic, Roel A. Ophoff, Phil Lee, Peter McGuffin, Gunnar Morken, George P. Patrinos, Alessandro Serretti, Cynthia Shannon Weickert, Pablo Cervantes, Bendik S. Winsvold, Tatiana Foroud, Tõnu Esko, Ulrich Schall, Michele T. Pato, Ji Hyun Baek, John R. Kelsoe, Olav B. Smeland, Janos Kalman, Eva C. Schulte, Joanna Hauser, Urs Heilbronner, Magnús Haraldsson, Martin Hautzinger, Lea Zillich, Eline J. Regeer, Douglas Blackwood, Laura J. Scott, Jordan W. Smoller, Michael J. Gandal, Marquis P. Vawter, Philip B. Mitchell, Ole Kristian Drange, Peter R. Schofield, Susanne Bengesser, Stefan Herms, George Kirov, Markus Leber, Louise Frisén, Thomas W. Mühleisen, Susan L. McElroy, Irwin D. Waldman, Wade H. Berrettini, Sally I. Sharp, Minsoo Kim, Lisa Jones, Eli A. Stahl, Hreinn Stefansson, Esben Agerbo, Dolores Malaspina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, Mullins N., Forstner A.J., O'Connell K.S., Coombes B., Coleman J.R.I., Qiao Z., Als T.D., Bigdeli T.B., Borte S., Bryois J., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Kim M., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Steinberg S., Trubetskoy V., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Agerbo E., Al Eissa M., Albani D., Alliey-Rodriguez N., Anjorin A., Antilla V., Antoniou A., Awasthi S., Baek J.H., Baekvad-Hansen M., Bass N., Bauer M., Beins E.C., Bergen S.E., Birner A., Bocker Pedersen C., Boen E., Boks M.P., Bosch R., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Budde M., Bybjerg-Grauholm J., Byerley W., Cairns M., Casas M., Cervantes P., Clarke T.-K., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Degenhardt F., Djurovic S., Dobbyn A.L., Douzenis A., Elvsashagen T., Escott-Price V., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frank J., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Giortz Pedersen M., Gizer I.R., Gordon S.D., Gordon-Smith K., Greenwood T.A., Grove J., Guzman-Parra J., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Herms S., Hoffmann P., Holmans P.A., Huckins L., Jamain S., Johnson J.S., Kalman J.L., Kamatani Y., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Kogevinas M., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Lawrence J., Leber M., Lee H.-J., Lee P.H., Levy S.E., Lewis C., Liao C., Lucae S., Lundberg M., MacIntyre D.J., Magnusson S.H., Maier W., Maihofer A., Malaspina D., Maratou E., Martinsson L., Mattheisen M., McCarroll S.A., McGregor N.W., McGuffin P., McKay J.D., Medeiros H., Medland S.E., Millischer V., Montgomery G.W., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Potash J.B., Quested D., Raj T., Rapaport M.H., DePaulo J.R., Regeer E.J., Rice J.P., Rivas F., Rivera M., Roth J., Roussos P., Ruderfer D.M., Sanchez-Mora C., Schulte E.C., Senner F., Sharp S., Shilling P.D., Sigurdsson E., Sirignano L., Slaney C., Smeland O.B., Smith D.J., Sobell J.L., Soholm Hansen C., Soler Artigas M., Spijker A.T., Stein D.J., Strauss J.S., Swiatkowska B., Terao C., Thorgeirsson T.E., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Walters J.T.R., Witt S.H., Xi S., Xu W., Yang J.M.K., Young A.H., Young H., Zandi P.P., Zhou H., Zillich L., Adolfsson R., Agartz I., Alda M., Alfredsson L., Babadjanova G., Backlund L., Baune B.T., Bellivier F., Bengesser S., Berrettini W.H., Blackwood D.H.R., Boehnke M., Borglum A.D., Breen G., Carr V.J., Catts S., Corvin A., Craddock N., Dannlowski U., Dikeos D., Esko T., Etain B., Ferentinos P., Frye M., Fullerton J.M., Gawlik M., Gershon E.S., Goes F.S., Green M.J., Grigoroiu-Serbanescu M., Hauser J., Henskens F., Hillert J., Hong K.S., Hougaard D.M., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Jones I., Jones L.A., Kahn R.S., Kelsoe J.R., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Lochner C., Loughland C., Martin N.G., Mathews C.A., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Michie P., Milani L., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Mowry B., Muller-Myhsok B., Myers R.M., Neale B.M., Nievergelt C.M., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Olsson T., Owen M.J., Paciga S.A., Pantelis C., Pato C., Pato M.T., Patrinos G.P., Perlis R.H., Posthuma D., Ramos-Quiroga J.A., Reif A., Reininghaus E.Z., Ribases M., Rietschel M., Ripke S., Rouleau G.A., Saito T., Schall U., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Scott R.J., Serretti A., Shannon Weickert C., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Streit F., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Waldman I.D., Weickert T.W., Werge T., Wray N.R., Zwart J.-A., Biernacka J.M., Nurnberger J.I., Cichon S., Edenberg H.J., Stahl E.A., McQuillin A., Di Florio A., Ophoff R.A., Andreassen O.A., IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etain, Bruno
Subjects: Multifactorial Inheritance, Bipolar Disorder, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Genome-wide association study, Major Histocompatibility Complex/genetics, Major Histocompatibility Complex, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH: Bipolar Disorder, Chromosomes, Human, Spectrum disorder, Genetics, 0303 health sciences, Bipolar Disorder/genetics, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, Phenotype, Schizophrenia, Synaptic signaling, Case-Control Studie, Human, Quantitative Trait Loci, Biology, MESH: Phenotype, MESH: Chromosomes, Human, Article, 03 medical and health sciences, MESH: Major Histocompatibility Complex, SDG 3 - Good Health and Well-being, ddc:570, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, Multifactorial Inheritance/genetics, MESH: Genome, Human, 030304 developmental biology, MESH: Humans, Genome, Human, Risk Factor, Chromosomes, Human/genetics, Mental illness, medicine.disease, MESH: Quantitative Trait Loci, Human genetics, Psychologie, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Genome-Wide Association Study, Expression quantitative trait loci, MESH: Multifactorial Inheritance, Quantitative Trait Loci/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: International audience; Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
Published: 2021
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36. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

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

Author: Cabana-Domínguez J, Bosch R, Soler Artigas M, Alemany S, Llonga N, Vilar-Ribó L, Carabí-Gassol P, Arribas L, Macias-Chimborazo V, Español-Martín G, Del Castillo C, Martínez L, Pagerols M, Pagespetit È, Prat R, Puigbó J, Ramos-Quiroga JA, Casas M, and Ribasés M
Subjects: Humans, Male, Child, Female, Academic Success, Schools, Adolescent, Genetic Predisposition to Disease genetics, Phenotype, Attention Deficit Disorder with Hyperactivity genetics, Autism Spectrum Disorder genetics, Multifactorial Inheritance genetics, Educational Status
Abstract: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are strongly associated with educational attainment (EA), but little is known about their genetic relationship with school performance and whether these links are explained, in part, by the genetic liability of EA. Here, we aim to dissect the polygenic contribution of ADHD and ASD to school performance, early manifestation of psychopathology and other psychiatric disorders and related traits by their relationship with EA. To do so, we tested the association of polygenic scores for EA, ADHD and ASD with school performance, assessed whether the contribution of the genetic liability of ADHD and ASD to school performance is influenced by the genetic liability of EA, and evaluated the role of EA in the genetic overlap between ADHD and ASD with early manifestation of psychopathology and other psychiatric disorders and related traits in a sample of 4,278 school-age children. The genetic liability for ADHD and ASD dissected by their relationship with EA show differences in their association with school performance and early manifestation of psychopathology, partly mediated by ADHD and ASD symptoms. Genetic variation with concordant effects in ASD and EA contributes to better school performance, while the genetic variation with discordant effects in ADHD or ASD and EA is associated with poor school performance and higher rates of emotional and behavioral problems. Our results strongly support the usage of the genetic load for EA to dissect the genetic and phenotypic heterogeneity of ADHD and ASD, which could help to fill the gap of knowledge of mechanisms underlying educational outcomes., (© 2024. The Author(s).)
Published: 2024
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38. Disentangling heterogeneity in substance use disorder: Insights from genome-wide polygenic scores.

Author: Vilar-Ribó L, Cabana-Domínguez J, Alemany S, Llonga N, Arribas L, Grau-López L, Daigre C, Cormand B, Fernàndez-Castillo N, Ramos-Quiroga JA, Soler Artigas M, and Ribasés M
Subjects: Humans, Male, Female, Adult, Genetic Predisposition to Disease, Middle Aged, Genome-Wide Association Study, Gene-Environment Interaction, Young Adult, Comorbidity, Mental Disorders genetics, Mental Disorders epidemiology, Substance-Related Disorders genetics, Substance-Related Disorders epidemiology, Multifactorial Inheritance, Phenotype
Abstract: Substance use disorder (SUD) is a global health problem with a significant impact on individuals and society. The presentation of SUD is diverse, involving various substances, ages at onset, comorbid conditions, and disease trajectories. Current treatments for SUD struggle to address this heterogeneity, resulting in high relapse rates. SUD often co-occurs with other psychiatric and mental health-related conditions that contribute to the heterogeneity of the disorder and predispose to adverse disease trajectories. Family and genetic studies highlight the role of genetic and environmental factors in the course of SUD, and point to a shared genetic liability between SUDs and comorbid psychopathology. In this study, we aimed to disentangle SUD heterogeneity using a deeply phenotyped SUD cohort and polygenic scores (PGSs) for psychiatric disorders and related traits. We explored associations between PGSs and various SUD-related phenotypes, as well as PGS-environment interactions using information on lifetime emotional, physical, and/or sexual abuse. Our results identify clusters of individuals who exhibit differences in their phenotypic profile and reveal different patterns of associations between SUD-related phenotypes and the genetic liability for mental health-related traits, which may help explain part of the heterogeneity observed in SUD. In our SUD sample, we found associations linking the genetic liability for attention-deficit hyperactivity disorder (ADHD) with lower educational attainment, the genetic liability for post-traumatic stress disorder (PTSD) with higher rates of unemployment, the genetic liability for educational attainment with lower rates of criminal records and unemployment, and the genetic liability for well-being with lower rates of outpatient treatments and fewer problems related to family and social relationships. We also found evidence of PGS-environment interactions showing that genetic liability for suicide attempts worsened the psychiatric status in SUD individuals with a history of emotional physical and/or sexual abuse. Collectively, these data contribute to a better understanding of the role of genetic liability for mental health-related conditions and adverse life experiences in SUD heterogeneity., (© 2024. The Author(s).)
Published: 2024
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39. Transcriptomic risk scores for attention deficit/hyperactivity disorder.

Author: Cabana-Domínguez J, Llonga N, Arribas L, Alemany S, Vilar-Ribó L, Demontis D, Fadeuilhe C, Corrales M, Richarte V, Børglum AD, Ramos-Quiroga JA, Soler Artigas M, and Ribasés M
Subjects: Humans, Genome-Wide Association Study, Leukocytes, Mononuclear, Risk Factors, Transcriptome genetics, Attention Deficit Disorder with Hyperactivity genetics
Abstract: Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. We performed a transcriptome-wide association study (TWAS) using the latest genome-wide association study (GWAS) meta-analysis, in 38,691 individuals with ADHD and 186,843 controls, and 14 gene-expression reference panels across multiple brain tissues and whole blood. Based on TWAS results, we selected subsets of genes and constructed transcriptomic risk scores (TRSs) for the disorder in peripheral blood mononuclear cells of individuals with ADHD and controls. We found evidence of association between ADHD and TRSs constructed using expression profiles from multiple brain areas, with individuals with ADHD carrying a higher burden of TRSs than controls. TRSs were uncorrelated with the polygenic risk score (PRS) for ADHD and, in combination with PRS, improved significantly the proportion of variance explained over the PRS-only model. These results support the complementary predictive potential of genetic and transcriptomic profiles in blood and underscore the potential utility of gene expression for risk prediction and deeper insight in molecular mechanisms underlying ADHD., (© 2023. The Author(s).)
Published: 2023
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40. Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan.

Author: Vilar-Ribó L, Cabana-Domínguez J, Martorell L, Ramos-Quiroga JA, Sanchez-Roige S, Palmer AA, Vilella E, Ribasés M, Muntané G, and Soler Artigas M
Subjects: Humans, Longevity genetics, Phenotype, Mendelian Randomization Analysis, Attention Deficit Disorder with Hyperactivity epidemiology, Attention Deficit Disorder with Hyperactivity genetics, Genome-Wide Association Study methods
Abstract: There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality. We confirmed a negative genetic correlation between ADHD and parental lifespan (rg = -0.36, P = 1.41e-16). Nineteen independent loci were jointly associated with both ADHD and parental lifespan, with most of the alleles that increased the risk for ADHD being associated with shorter lifespan. Fifteen loci were novel for ADHD and two were already present in the original GWAS on parental lifespan. Mendelian randomization analyses pointed towards a negative causal effect of ADHD liability on lifespan (P = 1.54e-06; Beta = -0.07), although these results were not confirmed by all sensitivity analyses performed, and further evidence is required. The present study provides the first evidence of a common genetic background between ADHD and lifespan, which may play a role in the reported effect of ADHD on premature mortality risk. These results are consistent with previous epidemiological data describing reduced lifespan in mental disorders and support that ADHD is an important health condition that could negatively affect future life outcomes., (© 2023. The Author(s).)
Published: 2023
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41. Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants.

Author: Alemany S, Soler-Artigas M, Cabana-Domínguez J, Fakhreddine D, Llonga N, Vilar-Ribó L, Rodríguez-Urrutia A, Palacio J, González-Castro AM, Lobo B, Alonso-Cotoner C, Simrén M, Santos J, Ramos-Quiroga JA, and Ribasés M
Subjects: Humans, Genome-Wide Association Study, Anxiety complications, Anxiety genetics, Comorbidity, Phenotype, Irritable Bowel Syndrome genetics, Irritable Bowel Syndrome complications, Irritable Bowel Syndrome psychology
Abstract: Background: Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them., Methods: We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date., Results: IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety., Conclusions: These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders., (© 2023. The Author(s).)
Published: 2023
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42. Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes.

Author: Soler Artigas M, Sánchez-Mora C, Rovira P, Vilar-Ribó L, Ramos-Quiroga JA, and Ribasés M
Subjects: Humans, Mendelian Randomization Analysis methods, Genome-Wide Association Study, Causality, Attention Deficit Disorder with Hyperactivity epidemiology, Attention Deficit Disorder with Hyperactivity genetics, Depressive Disorder, Major
Abstract: Background: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder caused by a combination of genetic and environmental factors and is often thought as an entry point into a negative life trajectory, including risk for comorbid disorders, poor educational achievement or low income. In the present study, we aimed to clarify the causal relationship between ADHD and a comprehensive range of related traits., Methods: We used genome-wide association study (GWAS) summary statistics for ADHD (n = 53 293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16 067 ≤n ≤766 345). To investigate their causal relationship with ADHD, we used two-sample Mendelian randomization (MR) with a range of sensitivity analyses, and validated MR findings using causal analysis using summary effect estimates (CAUSE), aiming to avoid potential false-positive results., Results: Our findings strengthen previous evidence of a causal effect of ADHD liability on smoking and major depression, and are consistent with a causal effect on odds of decreased average total household income [odds ratio (OR) = 0.966, 95% credible interval (CrI) = (0.954, 0.979)] and increased lifetime number of sexual partners [OR = 1.023, 95% CrI = (1.013, 1.033)]. We also found evidence for a causal effect on ADHD for liability of arm predicted mass and weight [OR = 1.452, 95% CrI = (1.307, 1.614) and OR = 1.430, 95% CrI = (1.326, 1.539), respectively] and time spent watching television [OR = 1.862, 95% CrI = (1.545, 2.246)], and evidence for a bidirectional effect for age of first sexual intercourse [beta = -0.058, 95% CrI = (-0.072, -0.044) and OR = 0.413, 95% CrI = (0.372, 0.457), respectively], odds of decreased age completed full-time education [OR = 0.972, 95% CrI = (0.962, 0.981) and OR = 0.435, 95% CrI = (0.356, 0.533), respectively] and years of schooling [beta = -0.036, 95% CrI = (-0.048, -0.024) and OR = 0.458, 95% CrI = (0.411, 0.511), respectively]., Conclusions: Our results may contribute to explain part of the widespread co-occurring traits and comorbid disorders across the lifespan of individuals with ADHD and may open new opportunities for developing preventive strategies for ADHD and for negative ADHD trajectories., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)
Published: 2023
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43. Author Correction: Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.

Author: Demontis D, Walters GB, Athanasiadis G, Walters R, Therrien K, Nielsen TT, Farajzadeh L, Voloudakis G, Bendl J, Zeng B, Zhang W, Grove J, Als TD, Duan J, Satterstrom FK, Bybjerg-Grauholm J, Bækved-Hansen M, Gudmundsson OO, Magnusson SH, Baldursson G, Davidsdottir K, Haraldsdottir GS, Agerbo E, Hoffman GE, Dalsgaard S, Martin J, Ribasés M, Boomsma DI, Soler Artigas M, Roth Mota N, Howrigan D, Medland SE, Zayats T, Rajagopal VM, Nordentoft M, Mors O, Hougaard DM, Mortensen PB, Daly MJ, Faraone SV, Stefansson H, Roussos P, Franke B, Werge T, Neale BM, Stefansson K, and Børglum AD
Published: 2023
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44. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.

Author: Demontis D, Walters GB, Athanasiadis G, Walters R, Therrien K, Nielsen TT, Farajzadeh L, Voloudakis G, Bendl J, Zeng B, Zhang W, Grove J, Als TD, Duan J, Satterstrom FK, Bybjerg-Grauholm J, Bækved-Hansen M, Gudmundsson OO, Magnusson SH, Baldursson G, Davidsdottir K, Haraldsdottir GS, Agerbo E, Hoffman GE, Dalsgaard S, Martin J, Ribasés M, Boomsma DI, Soler Artigas M, Roth Mota N, Howrigan D, Medland SE, Zayats T, Rajagopal VM, Nordentoft M, Mors O, Hougaard DM, Mortensen PB, Daly MJ, Faraone SV, Stefansson H, Roussos P, Franke B, Werge T, Neale BM, Stefansson K, and Børglum AD
Subjects: Humans, Brain, Cognition, Genetic Predisposition to Disease, Genome-Wide Association Study, Attention Deficit Disorder with Hyperactivity genetics
Abstract: Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2023
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45. Comprehensive analysis of omics data identifies relevant gene networks for Attention-Deficit/Hyperactivity Disorder (ADHD).

Author: Cabana-Domínguez J, Soler Artigas M, Arribas L, Alemany S, Vilar-Ribó L, Llonga N, Fadeuilhe C, Corrales M, Richarte V, Ramos-Quiroga JA, and Ribasés M
Subjects: Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukocytes, Mononuclear, Attention Deficit Disorder with Hyperactivity genetics, MicroRNAs genetics
Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder that results from the interaction of both genetic and environmental risk factors. Genome-wide association studies have started to identify multiple genetic risk loci associated with ADHD, however, the exact causal genes and biological mechanisms remain largely unknown. We performed a multi-step analysis to identify and characterize modules of co-expressed genes associated with ADHD using data from peripheral blood mononuclear cells of 270 ADHD cases and 279 controls. We identified seven ADHD-associated modules of co-expressed genes, some of them enriched in both genetic and epigenetic signatures for ADHD and in biological pathways relevant for psychiatric disorders, such as the regulation of gene expression, epigenetics and immune system. In addition, for some of the modules, we found evidence of potential regulatory mechanisms, including microRNAs and common genetic variants. In conclusion, our results point to promising genes and pathways for ADHD, supporting the use of peripheral blood to assess gene expression signatures in psychiatric disorders. Furthermore, they highlight that the combination of multi-omics signals provides deeper and broader insights into the biological mechanisms underlying ADHD., (© 2022. The Author(s).)
Published: 2022
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46. New Distance-Based approach for Genome-Wide Association Studies.

Author: Irigoien I, Cormand B, Soler-Artigas M, Sanchez-Mora C, Ramos-Quiroga JA, and Arenas C
Subjects: Humans, Alleles, Case-Control Studies, Genetic Predisposition to Disease genetics, Genotype, Genome-Wide Association Study methods, Polymorphism, Single Nucleotide genetics
Abstract: With the rise of genome-wide association studies (GWAS), the analysis of typical GWAS data sets with thousands of single-nucleotide polymorphisms (SNPs) has become crucial in biomedicine research. Here, we propose a new method to identify SNPs related to disease in case-control studies. The method, based on genetic distances between individuals, takes into account the possible population substructure, and avoids the issues of multiple testing. The method provides two ordered lists of SNPs; one with SNPs which minor alleles can be considered risk alleles for the disease, and another one with SNPs which minor alleles can be considered as protective. These two lists provide a useful tool to help the researcher to decide where to focus attention in a first stage.
Published: 2022
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47. Inhaled Loxapine as a Rapid Treatment for Agitation in Patients with Personality Disorder: A Prospective Study on the Effects of Time.

Author: Ferrer M, Soto-Angona Ó, Soler-Artigas M, Ibáñez P, Fadeuilhe C, Palma-Álvarez RF, Lidai R, Vargas-Cáceres S, Ángeles Torrecilla M, López A, and Ramos-Quiroga JA
Abstract: Objective: Agitation in patients diagnosed with personality disorders (PD) is one of the most frequent crises in emergency departments (ED). Although many medications have been tested, their effectiveness has been small or non-significant, and no specific drugs are supported by the available evidence. This study aimed to evaluate the efficacy of Inhaled loxapine (IL) as a therapeutic option for agitated patients with PD., Methods: A naturalistic, unicentric, prospective study was carried out. Thirty subjects diagnosed with PD and attending the ED with episodes of agitation were recruited most of whom were women diagnosed with Borderline Personality Disorder. Subjects were treated with a single dose of IL (9.1 mg). Efficacy was assessed with the Clinical Global Impression scale, the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) and the Agitation-Calmness Evaluation Scale (ACES). Patients were followed 60 minutes after administration to measure IL effect and its duration., Results: IL exhibited an overall efficacy in managing mild to severe agitation, with a quick onset of effect and persistence. 'Effect of time', where IL efficacy is maintained over time, is more marked in higher-severity agitation. No additional treatments were needed to improve agitation during the follow-up time., Conclusion: Results suggest that IL could be a safe and effective option to manage agitation in PD.
Published: 2022
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48. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.

Author: Mullins N, Kang J, Campos AI, Coleman JRI, Edwards AC, Galfalvy H, Levey DF, Lori A, Shabalin A, Starnawska A, Su MH, Watson HJ, Adams M, Awasthi S, Gandal M, Hafferty JD, Hishimoto A, Kim M, Okazaki S, Otsuka I, Ripke S, Ware EB, Bergen AW, Berrettini WH, Bohus M, Brandt H, Chang X, Chen WJ, Chen HC, Crawford S, Crow S, DiBlasi E, Duriez P, Fernández-Aranda F, Fichter MM, Gallinger S, Glatt SJ, Gorwood P, Guo Y, Hakonarson H, Halmi KA, Hwu HG, Jain S, Jamain S, Jiménez-Murcia S, Johnson C, Kaplan AS, Kaye WH, Keel PK, Kennedy JL, Klump KL, Li D, Liao SC, Lieb K, Lilenfeld L, Liu CM, Magistretti PJ, Marshall CR, Mitchell JE, Monson ET, Myers RM, Pinto D, Powers A, Ramoz N, Roepke S, Rozanov V, Scherer SW, Schmahl C, Sokolowski M, Strober M, Thornton LM, Treasure J, Tsuang MT, Witt SH, Woodside DB, Yilmaz Z, Zillich L, Adolfsson R, Agartz I, Air TM, Alda M, Alfredsson L, Andreassen OA, Anjorin A, Appadurai V, Soler Artigas M, Van der Auwera S, Azevedo MH, Bass N, Bau CHD, Baune BT, Bellivier F, Berger K, Biernacka JM, Bigdeli TB, Binder EB, Boehnke M, Boks MP, Bosch R, Braff DL, Bryant R, Budde M, Byrne EM, Cahn W, Casas M, Castelao E, Cervilla JA, Chaumette B, Cichon S, Corvin A, Craddock N, Craig D, Degenhardt F, Djurovic S, Edenberg HJ, Fanous AH, Foo JC, Forstner AJ, Frye M, Fullerton JM, Gatt JM, Gejman PV, Giegling I, Grabe HJ, Green MJ, Grevet EH, Grigoroiu-Serbanescu M, Gutierrez B, Guzman-Parra J, Hamilton SP, Hamshere ML, Hartmann A, Hauser J, Heilmann-Heimbach S, Hoffmann P, Ising M, Jones I, Jones LA, Jonsson L, Kahn RS, Kelsoe JR, Kendler KS, Kloiber S, Koenen KC, Kogevinas M, Konte B, Krebs MO, Landén M, Lawrence J, Leboyer M, Lee PH, Levinson DF, Liao C, Lissowska J, Lucae S, Mayoral F, McElroy SL, McGrath P, McGuffin P, McQuillin A, Medland SE, Mehta D, Melle I, Milaneschi Y, Mitchell PB, Molina E, Morken G, Mortensen PB, Müller-Myhsok B, Nievergelt C, Nimgaonkar V, Nöthen MM, O'Donovan MC, Ophoff RA, Owen MJ, Pato C, Pato MT, Penninx BWJH, Pimm J, Pistis G, Potash JB, Power RA, Preisig M, Quested D, Ramos-Quiroga JA, Reif A, Ribasés M, Richarte V, Rietschel M, Rivera M, Roberts A, Roberts G, Rouleau GA, Rovaris DL, Rujescu D, Sánchez-Mora C, Sanders AR, Schofield PR, Schulze TG, Scott LJ, Serretti A, Shi J, Shyn SI, Sirignano L, Sklar P, Smeland OB, Smoller JW, Sonuga-Barke EJS, Spalletta G, Strauss JS, Świątkowska B, Trzaskowski M, Turecki G, Vilar-Ribó L, Vincent JB, Völzke H, Walters JTR, Shannon Weickert C, Weickert TW, Weissman MM, Williams LM, Wray NR, Zai CC, Ashley-Koch AE, Beckham JC, Hauser ER, Hauser MA, Kimbrel NA, Lindquist JH, McMahon B, Oslin DW, Qin X, Agerbo E, Børglum AD, Breen G, Erlangsen A, Esko T, Gelernter J, Hougaard DM, Kessler RC, Kranzler HR, Li QS, Martin NG, McIntosh AM, Mors O, Nordentoft M, Olsen CM, Porteous D, Ursano RJ, Wasserman D, Werge T, Whiteman DC, Bulik CM, Coon H, Demontis D, Docherty AR, Kuo PH, Lewis CM, Mann JJ, Rentería ME, Smith DJ, Stahl EA, Stein MB, Streit F, Willour V, and Ruderfer DM
Subjects: Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors, Suicide, Attempted, Depressive Disorder, Major genetics, Mental Disorders genetics
Abstract: Background: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders., Methods: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors., Results: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged., Conclusions: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)
Published: 2022
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49. Genetic association study of childhood aggression across raters, instruments, and age.

Author: Ip HF, van der Laan CM, Krapohl EML, Brikell I, Sánchez-Mora C, Nolte IM, St Pourcain B, Bolhuis K, Palviainen T, Zafarmand H, Colodro-Conde L, Gordon S, Zayats T, Aliev F, Jiang C, Wang CA, Saunders G, Karhunen V, Hammerschlag AR, Adkins DE, Border R, Peterson RE, Prinz JA, Thiering E, Seppälä I, Vilor-Tejedor N, Ahluwalia TS, Day FR, Hottenga JJ, Allegrini AG, Rimfeld K, Chen Q, Lu Y, Martin J, Soler Artigas M, Rovira P, Bosch R, Español G, Ramos Quiroga JA, Neumann A, Ensink J, Grasby K, Morosoli JJ, Tong X, Marrington S, Middeldorp C, Scott JG, Vinkhuyzen A, Shabalin AA, Corley R, Evans LM, Sugden K, Alemany S, Sass L, Vinding R, Ruth K, Tyrrell J, Davies GE, Ehli EA, Hagenbeek FA, De Zeeuw E, Van Beijsterveldt TCEM, Larsson H, Snieder H, Verhulst FC, Amin N, Whipp AM, Korhonen T, Vuoksimaa E, Rose RJ, Uitterlinden AG, Heath AC, Madden P, Haavik J, Harris JR, Helgeland Ø, Johansson S, Knudsen GPS, Njolstad PR, Lu Q, Rodriguez A, Henders AK, Mamun A, Najman JM, Brown S, Hopfer C, Krauter K, Reynolds C, Smolen A, Stallings M, Wadsworth S, Wall TL, Silberg JL, Miller A, Keltikangas-Järvinen L, Hakulinen C, Pulkki-Råback L, Havdahl A, Magnus P, Raitakari OT, Perry JRB, Llop S, Lopez-Espinosa MJ, Bønnelykke K, Bisgaard H, Sunyer J, Lehtimäki T, Arseneault L, Standl M, Heinrich J, Boden J, Pearson J, Horwood LJ, Kennedy M, Poulton R, Eaves LJ, Maes HH, Hewitt J, Copeland WE, Costello EJ, Williams GM, Wray N, Järvelin MR, McGue M, Iacono W, Caspi A, Moffitt TE, Whitehouse A, Pennell CE, Klump KL, Burt SA, Dick DM, Reichborn-Kjennerud T, Martin NG, Medland SE, Vrijkotte T, Kaprio J, Tiemeier H, Davey Smith G, Hartman CA, Oldehinkel AJ, Casas M, Ribasés M, Lichtenstein P, Lundström S, Plomin R, Bartels M, Nivard MG, and Boomsma DI
Subjects: Adolescent, Child, Child, Preschool, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Infant, Retrospective Studies, Aggression, Mental Disorders
Abstract: Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG overall ) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG overall . The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (r g ) among rater-specific assessment of AGG ranged from r g = 0.46 between self- and teacher-assessment to r g = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong r g s with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r g = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG., (© 2021. The Author(s).)
Published: 2021
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50. Gut microbiota signature in treatment-naïve attention-deficit/hyperactivity disorder.

Author: Richarte V, Sánchez-Mora C, Corrales M, Fadeuilhe C, Vilar-Ribó L, Arribas L, Garcia E, Rosales-Ortiz SK, Arias-Vasquez A, Soler-Artigas M, Ribasés M, and Ramos-Quiroga JA
Subjects: Adolescent, Adult, Attention, Body Mass Index, Child, Humans, Young Adult, Attention Deficit Disorder with Hyperactivity, Gastrointestinal Microbiome, Neurodevelopmental Disorders
Abstract: Compelling evidence supports alterations in gut microbial diversity, bacterial composition, and/or relative abundance of several bacterial taxa in attention-deficit/hyperactivity disorder (ADHD). However, findings for ADHD are inconsistent among studies, and specific gut microbiome signatures for the disorder remain unknown. Given that previous studies have mainly focused on the pediatric form of the disorder and involved small sample sizes, we conducted the largest study to date to compare the gastrointestinal microbiome composition in 100 medication-naïve adults with ADHD and 100 sex-matched healthy controls. We found evidence that ADHD subjects have differences in the relative abundance of several microbial taxa. At the family level, our data support a lower relative abundance of Gracilibacteraceae and higher levels of Selenomonadaceae and Veillonellaceae in adults with ADHD. In addition, the ADHD group showed higher levels of Dialister and Megamonas and lower abundance of Anaerotaenia and Gracilibacter at the genus level. All four selected genera explained 15% of the variance of ADHD, and this microbial signature achieved an overall sensitivity of 74% and a specificity of 71% for distinguishing between ADHD patients and healthy controls. We also tested whether the selected genera correlate with age, body mass index (BMI), or scores of the ADHD rating scale but found no evidence of correlation between genera relative abundance and any of the selected traits. These results are in line with recent studies supporting gut microbiome alterations in neurodevelopment disorders, but further studies are needed to elucidate the role of the gut microbiota on the ADHD across the lifespan and its contribution to the persistence of the disorder from childhood to adulthood.
Published: 2021
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