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1. Genome-wide association meta-analysis of childhood and adolescent internalizing symptoms

Author

Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), Middeldorp, C. M. (Christel M.), Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), and Middeldorp, C. M. (Christel M.)

Abstract

Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84–2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%–8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| < 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42–0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Published
2022

2. Overview of CAPICE—childhood and adolescence psychopathology:unravelling the complex etiology by a large interdisciplinary collaboration in Europe—an EU Marie Skłodowska‑Curie International Training Network

Author

Rajula, H. S. (Hema Sekhar Reddy), Manchia, M. (Mirko), Agarwal, K. (Kratika), Akingbuwa, W. A. (Wonuola A.), Allegrini, A. G. (Andrea G.), Diemer, E. (Elizabeth), Doering, S. (Sabrina), Haan, E. (Elis), Jami, E. S. (Eshim S.), Karhunen, V. (Ville), Leone, M. (Marica), Schellhas, L. (Laura), Thompson, A. (Ashley), van den Berg, S. M. (Stéphanie M.), Bergen, S. E. (Sarah E.), Kuja-Halkola, R. (Ralf), Hammerschlag, A. R. (Anke R.), Järvelin, M. R. (Marjo Riitta), Leval, A. (Amy), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Mauri, M. (Matteo), Munafò, M. R. (Marcus R.), Myers, D. (David), Plomin, R. (Robert), Rimfeld, K. (Kaili), Tiemeier, H. (Henning), Ystrom, E. (Eivind), Fanos, V. (Vassilios), Bartels, M. (Meike), and Middeldorp, C. M. (Christel M.)

Subjects
Childhood and adolescence psychopathology, Depression, Psychiatric genetics, Attention deficit hyperactivity disorder (ADHD), Anxiety
Abstract

The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).

Published
2021

3. Overview of CAPICE—Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe—an EU Marie Skłodowska-Curie International Training Network

Author

Rajula, H.S.R. (Hema Sekhar Reddy), Manchia, M. (Mriko), Agarwal, K. (Kratika), Akingbuwa, W.A. (Wonuola A.), Allegrini, A.G. (Andrea G.), Diemer, E. (Elizabeth), Doering, S. (Sabrina), Haan, E. (Elis), Jami, E.S. (Eshim S.), Karhunen, V. (Ville), Leone, M. (Marica), Schellhas, L. (Laura), Thompson, A. (Ashley), Berg, S.M. (Stéphanie) van den, Bergen, S.E. (Sarah), Kuja-Halkola, R. (Ralf), Hammerschlag, A.R. (Anke R.), Järvelin, M.R. (Marjo Riitta), Leval, A. (Amy), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Mauri, M. (Matteo), Munafò, M.R. (Marcus), Myers, D. (David), Plomin, R. (Robert), Rimfeld, K. (Kaili), Tiemeier, H.W. (Henning), Ystrom, E. (Eivind), Fanos, V. (Vassilios), Bartels, M. (Meike), Middeldorp, C.M. (Christel M.), Rajula, H.S.R. (Hema Sekhar Reddy), Manchia, M. (Mriko), Agarwal, K. (Kratika), Akingbuwa, W.A. (Wonuola A.), Allegrini, A.G. (Andrea G.), Diemer, E. (Elizabeth), Doering, S. (Sabrina), Haan, E. (Elis), Jami, E.S. (Eshim S.), Karhunen, V. (Ville), Leone, M. (Marica), Schellhas, L. (Laura), Thompson, A. (Ashley), Berg, S.M. (Stéphanie) van den, Bergen, S.E. (Sarah), Kuja-Halkola, R. (Ralf), Hammerschlag, A.R. (Anke R.), Järvelin, M.R. (Marjo Riitta), Leval, A. (Amy), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Mauri, M. (Matteo), Munafò, M.R. (Marcus), Myers, D. (David), Plomin, R. (Robert), Rimfeld, K. (Kaili), Tiemeier, H.W. (Henning), Ystrom, E. (Eivind), Fanos, V. (Vassilios), Bartels, M. (Meike), and Middeldorp, C.M. (Christel M.)

Abstract

The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention defici

Published
2021
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4. Genetic associations between childhood psychopathology and adult depression and associated traits in 42 998 individuals:a meta-analysis

Author

Akingbuwa, W. A. (Wonuola A.), Hammerschlag, A. R. (Anke R.), Jami, E. S. (Eshim S.), Allegrini, A. G. (Andrea G.), Karhunen, V. (Ville), Sallis, H. (Hannah), Ask, H. (Helga), Askeland, R. B. (Ragna B.), Baselmans, B. (Bart), Diemer, E. (Elizabeth), Hagenbeek, F. A. (Fiona A.), Havdahl, A. (Alexandra), Hottenga, J.-J. (Jouke-Jan), Mbarek, H. (Hamdi), Rivadeneira, F. (Fernando), Tesli, M. (Martin), van Beijsterveldt, C. (Catharina), Breen, G. (Gerome), Lewis, C. M. (Cathryn M.), Thapar, A. (Anita), Boomsma, D. I. (Dorret I.), Kuja-Halkola, R. (Ralf), Reichborn-Kjennerud, T. (Ted), Magnus, P. (Per), Rimfeld, K. (Kaili), Ystrom, E. (Eivind), Järvelin, M.-R. (Marjo-Riitta), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Munafo, M. R. (Marcus R.), Plomin, R. (Robert), Tiemeier, H. (Henning), Nivard, M. G. (Michel G.), Bartels, M. (Meike), Middeldorp, C. M. (Christel M.), Akingbuwa, W. A. (Wonuola A.), Hammerschlag, A. R. (Anke R.), Jami, E. S. (Eshim S.), Allegrini, A. G. (Andrea G.), Karhunen, V. (Ville), Sallis, H. (Hannah), Ask, H. (Helga), Askeland, R. B. (Ragna B.), Baselmans, B. (Bart), Diemer, E. (Elizabeth), Hagenbeek, F. A. (Fiona A.), Havdahl, A. (Alexandra), Hottenga, J.-J. (Jouke-Jan), Mbarek, H. (Hamdi), Rivadeneira, F. (Fernando), Tesli, M. (Martin), van Beijsterveldt, C. (Catharina), Breen, G. (Gerome), Lewis, C. M. (Cathryn M.), Thapar, A. (Anita), Boomsma, D. I. (Dorret I.), Kuja-Halkola, R. (Ralf), Reichborn-Kjennerud, T. (Ted), Magnus, P. (Per), Rimfeld, K. (Kaili), Ystrom, E. (Eivind), Järvelin, M.-R. (Marjo-Riitta), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Munafo, M. R. (Marcus R.), Plomin, R. (Robert), Tiemeier, H. (Henning), Nivard, M. G. (Michel G.), Bartels, M. (Meike), and Middeldorp, C. M. (Christel M.)

Abstract

Importance: Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits. Objective: To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders. Design, Setting, and Participants: This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019. Exposures: Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI). Main Outcomes and Measures: Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater. Results: The sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023–0.042 [95% CI, 0.017–0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, −0.026 to −0.046 [95% CI, −0.020 to −0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations betwe

Published
2020

5. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Author

Vogelezang, S. (Suzanne), Bradfield, J. P. (Jonathan P.), Ahluwalia, T. S. (Tarunveer S.), Curtin, J. A. (John A.), Lakka, T. A. (Timo A.), Grarup, N. (Niels), Scholz, M. (Markus), van der Most, P. J. (Peter J.), Monnereau, C. (Claire), Stergiakouli, E. (Evie), Heiskala, A. (Anni), Horikoshi, M. (Momoko), Fedko, I. O. (Iryna O.), Vilor-Tejedor, N. (Natalia), Cousminer, D. L. (Diana L.), Standl, M. (Marie), Wang, C. A. (Carol A.), Viikari, J. (Jorma), Geller, F. (Frank), iniguez, C. (Carmen), Pitkanen, N. (Niina), Chesi, A. (Alessandra), Bacelis, J. (Jonas), Yengo, L. (Loic), Torrent, M. (Maties), Ntalla, I. (Ioanna), Helgeland, O. (Oyvind), Selzam, S. (Saskia), Vonk, J. M. (Judith M.), Zafarmand, M. H. (Mohammed H.), Heude, B. (Barbara), Farooqi, I. S. (Ismaa Sadaf), Alyass, A. (Akram), Beaumont, R. N. (Robin N.), Have, C. T. (Christian T.), Rzehak, P. (Peter), Bilbao, J. R. (Jose Ramon), Schnurr, T. M. (Theresia M.), Barroso, I. (Ines), Bonnelykke, K. (Klaus), Beilin, L. J. (Lawrence J.), Carstensen, L. (Lisbeth), Charles, M.-A. (Marie-Aline), Chawes, B. (Bo), Clement, K. (Karine), Closa-Monasterolo, R. (Ricardo), Custovic, A. (Adnan), Eriksson, J. G. (Johan G.), Escribano, J. (Joaquin), Groen-Blokhuis, M. (Maria), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Hakonarson, H. (Hakon), Hansen, T. (Torben), Hattersley, A. T. (Andrew T.), Hollensted, M. (Mette), Hottenga, J.-J. (Jouke-Jan), Hypponen, E. (Elina), Johansson, S. (Stefan), Joro, R. (Raimo), Kahonen, M. (Mika), Karhunen, V. (Ville), Kiess, W. (Wieland), Knight, B. A. (Bridget A.), Koletzko, B. (Berthold), Kuehnapfel, A. (Andreas), Landgraf, K. (Kathrin), Langhendries, J.-P. (Jean-Paul), Lehtimaki, T. (Terho), Leinonen, J. T. (Jaakko T.), Li, A. (Aihuali), Lindi, V. (Virpi), Lowry, E. (Estelle), Bustamante, M. (Mariona), Medina-Gomez, C. (Carolina), Melbye, M. (Mads), Michaelsen, K. F. (Kim F.), Morgen, C. S. (Camilla S.), Mori, T. A. (Trevor A.), Nielsen, T. R. (Tenna R. H.), Niinikoski, H. (Harri), Oldehinkel, A. J. (Albertine J.), Pahkala, K. (Katja), Panoutsopoulou, K. (Kalliope), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Power, C. (Christine), Reijneveld, S. A. (Sijmen A.), Rivadeneira, F. (Fernando), Simpson, A. (Angela), Sly, P. D. (Peter D.), Stokholm, J. (Jakob), Teo, K. K. (Kook K.), Thiering, E. (Elisabeth), Timpson, N. J. (Nicholas J.), Uitterlinden, A. G. (Andre G.), van Beijsterveldt, C. E. (Catharina E. M.), van Schaik, B. D. (Barbera D. C.), Vaudel, M. (Marc), Verduci, E. (Elvira), Vinding, R. K. (Rebecca K.), Vogel, M. (Mandy), Zeggini, E. (Eleftheria), Sebert, S. (Sylvain), Lind, M. V. (Mads V.), Brown, C. D. (Christopher D.), Santa-Marina, L. (Loreto), Reischl, E. (Eva), Frithioff-Bojsoe, C. (Christine), Meyre, D. (David), Wheeler, E. (Eleanor), Ong, K. (Ken), Nohr, E. A. (Ellen A.), Vrijkotte, T. G. (Tanja G. M.), Koppelman, G. H. (Gerard H.), Plomin, R. (Robert), Njolstad, P. R. (Pal R.), Dedoussis, G. D. (George D.), Froguel, P. (Philippe), Sorensen, T. I. (Thorkild I. A.), Jacobsson, B. (Bo), Freathy, R. M. (Rachel M.), Zemel, B. S. (Babette S.), Raitakari, O. (Olli), Vrijheid, M. (Martine), Feenstra, B. (Bjarke), Lyytikainen, L.-P. (Leo-Pekka), Snieder, H. (Harold), Kirsten, H. (Holger), Holt, P. G. (Patrick G.), Heinrich, J. (Joachim), Widen, E. (Elisabeth), Sunyer, J. (Jordi), Boomsma, D. I. (Dorret I.), Jarvelin, M.-R. (Marjo-Riitta), Koerner, A. (Antje), Davey Smith, G. (George), Holm, J.-C. (Jens-Christian), Atalay, M. (Mustafa), Murray, C. (Clare), Bisgaard, H. (Hans), McCarthy, M. I. (Mark I.), Jaddoe, V. W. (Vincent W. V.), Grant, S. F. (Struan F. A.), Felix, J. F. (Janine F.), Vogelezang, S. (Suzanne), Bradfield, J. P. (Jonathan P.), Ahluwalia, T. S. (Tarunveer S.), Curtin, J. A. (John A.), Lakka, T. A. (Timo A.), Grarup, N. (Niels), Scholz, M. (Markus), van der Most, P. J. (Peter J.), Monnereau, C. (Claire), Stergiakouli, E. (Evie), Heiskala, A. (Anni), Horikoshi, M. (Momoko), Fedko, I. O. (Iryna O.), Vilor-Tejedor, N. (Natalia), Cousminer, D. L. (Diana L.), Standl, M. (Marie), Wang, C. A. (Carol A.), Viikari, J. (Jorma), Geller, F. (Frank), iniguez, C. (Carmen), Pitkanen, N. (Niina), Chesi, A. (Alessandra), Bacelis, J. (Jonas), Yengo, L. (Loic), Torrent, M. (Maties), Ntalla, I. (Ioanna), Helgeland, O. (Oyvind), Selzam, S. (Saskia), Vonk, J. M. (Judith M.), Zafarmand, M. H. (Mohammed H.), Heude, B. (Barbara), Farooqi, I. S. (Ismaa Sadaf), Alyass, A. (Akram), Beaumont, R. N. (Robin N.), Have, C. T. (Christian T.), Rzehak, P. (Peter), Bilbao, J. R. (Jose Ramon), Schnurr, T. M. (Theresia M.), Barroso, I. (Ines), Bonnelykke, K. (Klaus), Beilin, L. J. (Lawrence J.), Carstensen, L. (Lisbeth), Charles, M.-A. (Marie-Aline), Chawes, B. (Bo), Clement, K. (Karine), Closa-Monasterolo, R. (Ricardo), Custovic, A. (Adnan), Eriksson, J. G. (Johan G.), Escribano, J. (Joaquin), Groen-Blokhuis, M. (Maria), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Hakonarson, H. (Hakon), Hansen, T. (Torben), Hattersley, A. T. (Andrew T.), Hollensted, M. (Mette), Hottenga, J.-J. (Jouke-Jan), Hypponen, E. (Elina), Johansson, S. (Stefan), Joro, R. (Raimo), Kahonen, M. (Mika), Karhunen, V. (Ville), Kiess, W. (Wieland), Knight, B. A. (Bridget A.), Koletzko, B. (Berthold), Kuehnapfel, A. (Andreas), Landgraf, K. (Kathrin), Langhendries, J.-P. (Jean-Paul), Lehtimaki, T. (Terho), Leinonen, J. T. (Jaakko T.), Li, A. (Aihuali), Lindi, V. (Virpi), Lowry, E. (Estelle), Bustamante, M. (Mariona), Medina-Gomez, C. (Carolina), Melbye, M. (Mads), Michaelsen, K. F. (Kim F.), Morgen, C. S. (Camilla S.), Mori, T. A. (Trevor A.), Nielsen, T. R. (Tenna R. H.), Niinikoski, H. (Harri), Oldehinkel, A. J. (Albertine J.), Pahkala, K. (Katja), Panoutsopoulou, K. (Kalliope), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Power, C. (Christine), Reijneveld, S. A. (Sijmen A.), Rivadeneira, F. (Fernando), Simpson, A. (Angela), Sly, P. D. (Peter D.), Stokholm, J. (Jakob), Teo, K. K. (Kook K.), Thiering, E. (Elisabeth), Timpson, N. J. (Nicholas J.), Uitterlinden, A. G. (Andre G.), van Beijsterveldt, C. E. (Catharina E. M.), van Schaik, B. D. (Barbera D. C.), Vaudel, M. (Marc), Verduci, E. (Elvira), Vinding, R. K. (Rebecca K.), Vogel, M. (Mandy), Zeggini, E. (Eleftheria), Sebert, S. (Sylvain), Lind, M. V. (Mads V.), Brown, C. D. (Christopher D.), Santa-Marina, L. (Loreto), Reischl, E. (Eva), Frithioff-Bojsoe, C. (Christine), Meyre, D. (David), Wheeler, E. (Eleanor), Ong, K. (Ken), Nohr, E. A. (Ellen A.), Vrijkotte, T. G. (Tanja G. M.), Koppelman, G. H. (Gerard H.), Plomin, R. (Robert), Njolstad, P. R. (Pal R.), Dedoussis, G. D. (George D.), Froguel, P. (Philippe), Sorensen, T. I. (Thorkild I. A.), Jacobsson, B. (Bo), Freathy, R. M. (Rachel M.), Zemel, B. S. (Babette S.), Raitakari, O. (Olli), Vrijheid, M. (Martine), Feenstra, B. (Bjarke), Lyytikainen, L.-P. (Leo-Pekka), Snieder, H. (Harold), Kirsten, H. (Holger), Holt, P. G. (Patrick G.), Heinrich, J. (Joachim), Widen, E. (Elisabeth), Sunyer, J. (Jordi), Boomsma, D. I. (Dorret I.), Jarvelin, M.-R. (Marjo-Riitta), Koerner, A. (Antje), Davey Smith, G. (George), Holm, J.-C. (Jens-Christian), Atalay, M. (Mustafa), Murray, C. (Clare), Bisgaard, H. (Hans), McCarthy, M. I. (Mark I.), Jaddoe, V. W. (Vincent W. V.), Grant, S. F. (Struan F. A.), and Felix, J. F. (Janine F.)

Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

Published
2020

6. Childhood aggression and the co-occurrence of behavioural and emotional problems

Author

Bartels, M. (Meike), Hendriks, A. (Anne), Mauri, M. (Matteo), Krapohl, E. (Eva), Whipp, A. (Alyce), Bolhuis, K. (Koen), Conde, L.C. (Lucia Colodro), Luningham, J. (Justin), Fung Ip, H. (Hill), Hagenbeek, F. (Fiona), Roetman, P. (Peter), Gatej, R. (Raluca), Lamers, A. (Audri), Nivard, M. (Michel), Dongen, J. (Jenny) van, Lu, Y. (Yi), Middeldorp, C.M. (Christel), Beijsterveldt, C.E.M. (Toos) van, Vermeiren, R.R.J.M. (Robert R.J.M.), Hankemeijer, T. (Thomas), Kluft, C. (Cees), Medland, S.E. (Sarah), Lundström, S. (Sebastian), Rose, R.J. (Richard), Pulkkinen, L. (Lea), Vuoksimaa, E. (Eero), Korhonen, T. (Tellervo), Martin, N.G. (Nicholas), Lubke, G.H. (Gitta), Finkenauer, C. (Catrin), Fanos, V. (Vassilios), Tiemeier, H.W. (Henning), Lichtenstein, P. (Paul), Plomin, R. (Robert), Kaprio, J. (Jaakko), Boomsma, D.I. (Dorret), Bartels, M. (Meike), Hendriks, A. (Anne), Mauri, M. (Matteo), Krapohl, E. (Eva), Whipp, A. (Alyce), Bolhuis, K. (Koen), Conde, L.C. (Lucia Colodro), Luningham, J. (Justin), Fung Ip, H. (Hill), Hagenbeek, F. (Fiona), Roetman, P. (Peter), Gatej, R. (Raluca), Lamers, A. (Audri), Nivard, M. (Michel), Dongen, J. (Jenny) van, Lu, Y. (Yi), Middeldorp, C.M. (Christel), Beijsterveldt, C.E.M. (Toos) van, Vermeiren, R.R.J.M. (Robert R.J.M.), Hankemeijer, T. (Thomas), Kluft, C. (Cees), Medland, S.E. (Sarah), Lundström, S. (Sebastian), Rose, R.J. (Richard), Pulkkinen, L. (Lea), Vuoksimaa, E. (Eero), Korhonen, T. (Tellervo), Martin, N.G. (Nicholas), Lubke, G.H. (Gitta), Finkenauer, C. (Catrin), Fanos, V. (Vassilios), Tiemeier, H.W. (Henning), Lichtenstein, P. (Paul), Plomin, R. (Robert), Kaprio, J. (Jaakko), and Boomsma, D.I. (Dorret)

Abstract

Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopa

Published
2018
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7. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Author

Iglesias, A.I. (Adriana I.), Mishra, A. (Aniket), Vitart, V. (Veronique), Bykhovskaya, Y. (Yelena), Höhn, R. (René), Springelkamp, H. (Henriët), Cuellar-Partida, G. (Gabriel), Gharahkhani, P. (Puya), Bailey, J.N.C. (Jessica N. Cooke), Willoughby, C.E. (Colin E.), Li, X. (Xiaohui), Yazar, S. (Seyhan), Nag, A. (Abhishek), Khawaja, A.P. (Anthony), Polasek, O. (Ozren), Siscovick, D.S. (David), Mitchell, P. (Paul), Tham, Y.C. (Yih Chung), Haines, J.L. (Jonathan), Kearns, L.S. (Lisa S.), Hayward, C. (Caroline), Shi, Y. (Yuan), Van Leeuwen, E.M. (Elisabeth M.), Taylor, K.D. (Kent), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A. (Ananth), Sim, X. (Xueling), Bonnemaijer, P.W.M. (Pieter), Rotter, J.I. (Jerome I.), Martin, N.G. (Nicholas G.), Zeller, T. (Tanja), Mills, R.A. (Richard), Staffieri, S.E. (Sandra E.), Jonas, J.B. (Jost B.), Schmidtmann, I. (Irene), Boutin, T. (Thibaud), Kang, J.H. (Jae H.), Lucas, S.E.M. (Sionne E.M.), Wong, T.Y. (Tien Yin), Beutel, M.E. (Manfred E.), Wilson, J.F. (James F.), Allingham, R.R. (R Rand), Brilliant, M.H. (Murray H.), Budenz, D.L. (Donald L.), Christen, W.G. (William G.), Fingert, J. (John), Friedman, D.S. (David), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Hauser, M.A. (Michael), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Loomis, S.J. (Stephanie J.), Moroi, S.E. (Sayoko), Pericak-Vance, M.A. (Margaret), Realini, A. (Anthony), Richards, J.E. (Julia E.), Schuman, J.S. (Joel S.), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Zack, D.J. (Donald), Zhang, K. (Kang), Donnelly, P. (Peter), Barroso, I.E. (Inês), Blackwell, J.M. (Jenefer M.), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panos), Duncanson, A. (Audrey), Jankowski, J. (Janusz), Markus, H.S. (Hugh), Mathew, J. (Joseph), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Wood, N.W. (Nicholas W.), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Langford, C. (Cordelia), Hunt, S.E. (Sarah E.), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, P. (Patrick), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Uitterlinden, A.G. (André), Vithana, E.N. (Eranga), Foster, P.J. (Paul), Hysi, P.G. (Pirro), Hewitt, A.W. (Alex W.), Khor, C.C., Pasquale, L.R. (Louis), Montgomery, G.W. (Grant W.), Klaver, C.C.W. (Caroline), Aung, T. (Tin), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Hammond, C.J. (Christopher), Cheng, C.-Y. (Ching-Yu), Craig, J.E. (Jamie), Rabinowitz, Y.S. (Yaron), Wiggs, J.L. (Janey L.), Burdon, K.P. (Kathryn), Duijn, C.M. (Cornelia) van, MacGregor, S. (Stuart), Iglesias, A.I. (Adriana I.), Mishra, A. (Aniket), Vitart, V. (Veronique), Bykhovskaya, Y. (Yelena), Höhn, R. (René), Springelkamp, H. (Henriët), Cuellar-Partida, G. (Gabriel), Gharahkhani, P. (Puya), Bailey, J.N.C. (Jessica N. Cooke), Willoughby, C.E. (Colin E.), Li, X. (Xiaohui), Yazar, S. (Seyhan), Nag, A. (Abhishek), Khawaja, A.P. (Anthony), Polasek, O. (Ozren), Siscovick, D.S. (David), Mitchell, P. (Paul), Tham, Y.C. (Yih Chung), Haines, J.L. (Jonathan), Kearns, L.S. (Lisa S.), Hayward, C. (Caroline), Shi, Y. (Yuan), Van Leeuwen, E.M. (Elisabeth M.), Taylor, K.D. (Kent), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A. (Ananth), Sim, X. (Xueling), Bonnemaijer, P.W.M. (Pieter), Rotter, J.I. (Jerome I.), Martin, N.G. (Nicholas G.), Zeller, T. (Tanja), Mills, R.A. (Richard), Staffieri, S.E. (Sandra E.), Jonas, J.B. (Jost B.), Schmidtmann, I. (Irene), Boutin, T. (Thibaud), Kang, J.H. (Jae H.), Lucas, S.E.M. (Sionne E.M.), Wong, T.Y. (Tien Yin), Beutel, M.E. (Manfred E.), Wilson, J.F. (James F.), Allingham, R.R. (R Rand), Brilliant, M.H. (Murray H.), Budenz, D.L. (Donald L.), Christen, W.G. (William G.), Fingert, J. (John), Friedman, D.S. (David), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Hauser, M.A. (Michael), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Loomis, S.J. (Stephanie J.), Moroi, S.E. (Sayoko), Pericak-Vance, M.A. (Margaret), Realini, A. (Anthony), Richards, J.E. (Julia E.), Schuman, J.S. (Joel S.), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Zack, D.J. (Donald), Zhang, K. (Kang), Donnelly, P. (Peter), Barroso, I.E. (Inês), Blackwell, J.M. (Jenefer M.), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panos), Duncanson, A. (Audrey), Jankowski, J. (Janusz), Markus, H.S. (Hugh), Mathew, J. (Joseph), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Wood, N.W. (Nicholas W.), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Langford, C. (Cordelia), Hunt, S.E. (Sarah E.), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, P. (Patrick), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Uitterlinden, A.G. (André), Vithana, E.N. (Eranga), Foster, P.J. (Paul), Hysi, P.G. (Pirro), Hewitt, A.W. (Alex W.), Khor, C.C., Pasquale, L.R. (Louis), Montgomery, G.W. (Grant W.), Klaver, C.C.W. (Caroline), Aung, T. (Tin), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Hammond, C.J. (Christopher), Cheng, C.-Y. (Ching-Yu), Craig, J.E. (Jamie), Rabinowitz, Y.S. (Yaron), Wiggs, J.L. (Janey L.), Burdon, K.P. (Kathryn), Duijn, C.M. (Cornelia) van, and MacGregor, S. (Stuart)

Abstract

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Published
2018
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8. Genome-wide association meta- Analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Author

Sniekers, S. (Suzanne), Stringer, S. (Sven), Watanabe, K. (Kyoko), Jansen, P.R. (Philip), Coleman, J.R.I. (Jonathan R I), Krapohl, E. (Eva), Taskesen, E. (Erdogan), Hammerschlag, A.R. (Anke R.), Okbay, A. (Aysu), Zabaneh, D. (Delilah), Amin, N. (Najaf), Breen, G. (Gerome), Cesarini, D. (David), Chabris, C.F. (Christopher F), Iacono, W.G. (William), Ikram, M.A. (Arfan), Johannesson, M. (Magnus), Koellinger, P. (Philipp), Lee, J.J. (James J.), Magnusson, P.K. (Patrik), McGue, M. (Matt), Miller, M. (Mike), Ollier, W.E.R. (William), Payton, A. (Antony), Pendleton, N. (Neil), Plomin, R. (Robert), Rietveld, C.A. (Niels), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, Posthuma, D. (Danielle), Sniekers, S. (Suzanne), Stringer, S. (Sven), Watanabe, K. (Kyoko), Jansen, P.R. (Philip), Coleman, J.R.I. (Jonathan R I), Krapohl, E. (Eva), Taskesen, E. (Erdogan), Hammerschlag, A.R. (Anke R.), Okbay, A. (Aysu), Zabaneh, D. (Delilah), Amin, N. (Najaf), Breen, G. (Gerome), Cesarini, D. (David), Chabris, C.F. (Christopher F), Iacono, W.G. (William), Ikram, M.A. (Arfan), Johannesson, M. (Magnus), Koellinger, P. (Philipp), Lee, J.J. (James J.), Magnusson, P.K. (Patrik), McGue, M. (Matt), Miller, M. (Mike), Ollier, W.E.R. (William), Payton, A. (Antony), Pendleton, N. (Neil), Plomin, R. (Robert), Rietveld, C.A. (Niels), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, and Posthuma, D. (Danielle)

Abstract

Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta- A nalysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.

Published
2017
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9. A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts

Author

Middeldorp, C.M. (Christel), Hammerschlag, A.R. (Anke R.), Ouwens, K.G. (Klaasjan), Groen-Blokhuis, M. (Maria), St Pourcain, B. (Beate), Greven, C.U. (Corina U.), Pappa, M. (Magda), Tiesler, C.M.T. (Carla M.T.), Ang, W.Q. (Wei), Nolte, I.M. (Ilja), Vilor-Tejedor, N. (Natàlia), Bacelis, J. (Jonas), Ebejer, J.L. (Jane L.), Zhao, H. (Huiying), Davies, G.E. (Gareth), Ehli, E.A. (Erik), Evans, D.M. (David), Fedko, I.O. (Iryna O.), Guxens Junyent, M. (Mònica), Hottenga, J.J. (Jouke Jan), Hudziak, J.J. (James), Juqessur, A. (Astanand), Kemp, J.P. (John), Krapohl, E. (Eva), Martin, N.G. (Nicholas), Murcia, M. (Mario), Myhre, R. (Ronny), Ormel, J. (Johan), Ring, S.M. (Susan), Standl, E. (Eberhard), Stergiakouli, E. (Evangelia), Stoltenberg, C. (Camilla), Thiering, E. (Elisabeth), Timpson, N.J. (Nicholas), Trzaskowski, M. (Maciej), Most, P.J. (Peter) van der, Wang, C.A. (Carol A.), Nyholt, D.R. (Dale), Medland, S.E. (Sarah), Neale, B.M. (Benjamin), Jacobsson, B. (Bo), Sunyer, J. (Jordi), Hartman, C.A. (C.), Whitehouse, A.J.O. (Andrew), Pennell, C.E. (Craig), Heinrich, J. (Joachim), Plomin, R. (Robert), Smith, A.V. (Davey), Tiemeier, H.W. (Henning), Posthuma, D. (Danielle), Boomsma, D.I. (Dorret), Middeldorp, C.M. (Christel), Hammerschlag, A.R. (Anke R.), Ouwens, K.G. (Klaasjan), Groen-Blokhuis, M. (Maria), St Pourcain, B. (Beate), Greven, C.U. (Corina U.), Pappa, M. (Magda), Tiesler, C.M.T. (Carla M.T.), Ang, W.Q. (Wei), Nolte, I.M. (Ilja), Vilor-Tejedor, N. (Natàlia), Bacelis, J. (Jonas), Ebejer, J.L. (Jane L.), Zhao, H. (Huiying), Davies, G.E. (Gareth), Ehli, E.A. (Erik), Evans, D.M. (David), Fedko, I.O. (Iryna O.), Guxens Junyent, M. (Mònica), Hottenga, J.J. (Jouke Jan), Hudziak, J.J. (James), Juqessur, A. (Astanand), Kemp, J.P. (John), Krapohl, E. (Eva), Martin, N.G. (Nicholas), Murcia, M. (Mario), Myhre, R. (Ronny), Ormel, J. (Johan), Ring, S.M. (Susan), Standl, E. (Eberhard), Stergiakouli, E. (Evangelia), Stoltenberg, C. (Camilla), Thiering, E. (Elisabeth), Timpson, N.J. (Nicholas), Trzaskowski, M. (Maciej), Most, P.J. (Peter) van der, Wang, C.A. (Carol A.), Nyholt, D.R. (Dale), Medland, S.E. (Sarah), Neale, B.M. (Benjamin), Jacobsson, B. (Bo), Sunyer, J. (Jordi), Hartman, C.A. (C.), Whitehouse, A.J.O. (Andrew), Pennell, C.E. (Craig), Heinrich, J. (Joachim), Plomin, R. (Robert), Smith, A.V. (Davey), Tiemeier, H.W. (Henning), Posthuma, D. (Danielle), and Boomsma, D.I. (Dorret)

Abstract

Objective The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46 × 10−6 and 2.66 × 10−6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants.

Published
2016
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10. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author

Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), Vatavuk, Z. (Zoran), Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), and Vatavuk, Z. (Zoran)

Abstract

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

Published
2016
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11. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

Author

Felix, J.F. (Janine), Bradfield, J.P. (Jonathan), Poppelaars-Monnereau, C. (Claire), Valk, R.J.P. (Ralf) van der, Stergiakouli, E. (Evie), Chesi, A. (Alessandra), Gaillard, R. (Romy), Feenstra, B. (Bjarke), Thiering, E. (Elisabeth), Kreiner-Møller, E. (Eskil), Mahajan, A. (Anubha), Pitkänen, N. (Niina), Joro, R. (Raimo), Cavadino, A. (Alana), Huikari, V. (Ville), Franks, S. (Steve), Groen-Blokhuis, M. (Maria), Cousminer, D.L. (Diana), Marsh, J.A. (Julie), Lehtimäki, T. (Terho), Curtin, J.A. (John), Vioque, J. (Jesus), Ahluwalia, T.S. (Tarunveer Singh), Myhre, R. (Ronny), Price, T.S. (Thomas), Vilor-Tejedor, N. (Natalia), Yengo, L. (Loic), Grarup, N. (Niels), Ntalla, I. (Ioanna), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Bisgaard, H. (Hans), Blakemore, A.I.F. (Alexandra), Bonnefond, A. (Amélie), Carstensen, L. (Lisbeth), Eriksson, J.G. (Johan G.), Flexeder, C. (Claudia), Franke, L. (Lude), Geller, F. (Frank), Geserick, M. (Mandy), Hartikainen, A.L., Haworth, C.M.A. (Claire M.), Hirschhorn, J.N. (Joel N.), Hofman, A. (Albert), Holm, J.-C. (Jens-Christian), Horikoshi, M. (Momoko), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Kadarmideen, H.N. (Haja N.), Kähönen, M. (Mika), Kiess, W. (Wieland), Lakka, T.A. (Timo), Lewin, A. (Alex), Liang, L. (Liming), Lyytikäinen, L.-P. (Leo-Pekka), Ma, B. (Baoshan), Magnus, P. (Per), McCormack, S.E. (Shana E.), Mcmahon, G. (George), Mentch, F.D. (Frank), Middeldorp, C.M. (Christel), Murray, C.S. (Clare S.), Pahkala, K. (Katja), Pers, T.H. (Tune), Pfäffle, R. (Roland), Postma, D.S. (Dirkje), Power, C. (Christine), Simpson, A. (Angela), Sengpiel, V. (Verena), Tiesler, C. (Carla), Torrent, M. (Maties), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Vinding, R. (Rebecca), Waage, J. (Johannes), Wardle, J. (Jane), Zeggini, E. (Eleftheria), Zemel, B.S. (Babette S.), Dedoussis, G.V. (George), Pedersen, O. (Oluf), Froguel, P. (Philippe), Sunyer, J. (Jordi), Plomin, R. (Robert), Jacobsson, B. (Bo), Hansen, T. (Torben), Gonzalez, J.R. (Juan R.), Custovic, A. (Adnan), Raitakari, O.T. (Olli T.), Pennell, C.E. (Craig), Widén, E. (Elisabeth), Boomsma, D.I. (Dorret), Koppelman, G.H. (Gerard), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Hypponen, E. (Elina), McCarthy, M.I. (Mark), Lindi, V. (Virpi), Harri, N. (Niinikoski), Körner, A. (Antje), Bønnelykke, K. (Klaus), Heinrich, J. (Joachim), Melbye, M. (Mads), Rivadeneira Ramirez, F. (Fernando), Hakonarson, H. (Hakon), Ring, S.M. (Susan), Smith, A.V. (Davey), Sørensen, T.I.A. (Thorkild I.A.), Timpson, N.J. (Nicholas), Grant, S.F.A. (Struan), Jaddoe, V.W.V. (Vincent), Kalkwarf, H.J. (Heidi J.), Lappe, J.M. (Joan M.), Gilsanz, V. (Vicente), Oberfield, S.E. (Sharon E.), Shepherd, J.A. (John A.), Kelly, A. (Andrea), Felix, J.F. (Janine), Bradfield, J.P. (Jonathan), Poppelaars-Monnereau, C. (Claire), Valk, R.J.P. (Ralf) van der, Stergiakouli, E. (Evie), Chesi, A. (Alessandra), Gaillard, R. (Romy), Feenstra, B. (Bjarke), Thiering, E. (Elisabeth), Kreiner-Møller, E. (Eskil), Mahajan, A. (Anubha), Pitkänen, N. (Niina), Joro, R. (Raimo), Cavadino, A. (Alana), Huikari, V. (Ville), Franks, S. (Steve), Groen-Blokhuis, M. (Maria), Cousminer, D.L. (Diana), Marsh, J.A. (Julie), Lehtimäki, T. (Terho), Curtin, J.A. (John), Vioque, J. (Jesus), Ahluwalia, T.S. (Tarunveer Singh), Myhre, R. (Ronny), Price, T.S. (Thomas), Vilor-Tejedor, N. (Natalia), Yengo, L. (Loic), Grarup, N. (Niels), Ntalla, I. (Ioanna), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Bisgaard, H. (Hans), Blakemore, A.I.F. (Alexandra), Bonnefond, A. (Amélie), Carstensen, L. (Lisbeth), Eriksson, J.G. (Johan G.), Flexeder, C. (Claudia), Franke, L. (Lude), Geller, F. (Frank), Geserick, M. (Mandy), Hartikainen, A.L., Haworth, C.M.A. (Claire M.), Hirschhorn, J.N. (Joel N.), Hofman, A. (Albert), Holm, J.-C. (Jens-Christian), Horikoshi, M. (Momoko), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Kadarmideen, H.N. (Haja N.), Kähönen, M. (Mika), Kiess, W. (Wieland), Lakka, T.A. (Timo), Lewin, A. (Alex), Liang, L. (Liming), Lyytikäinen, L.-P. (Leo-Pekka), Ma, B. (Baoshan), Magnus, P. (Per), McCormack, S.E. (Shana E.), Mcmahon, G. (George), Mentch, F.D. (Frank), Middeldorp, C.M. (Christel), Murray, C.S. (Clare S.), Pahkala, K. (Katja), Pers, T.H. (Tune), Pfäffle, R. (Roland), Postma, D.S. (Dirkje), Power, C. (Christine), Simpson, A. (Angela), Sengpiel, V. (Verena), Tiesler, C. (Carla), Torrent, M. (Maties), Uitterlinden, A.G. (André), Meurs, J.B.J. (Joyce) van, Vinding, R. (Rebecca), Waage, J. (Johannes), Wardle, J. (Jane), Zeggini, E. (Eleftheria), Zemel, B.S. (Babette S.), Dedoussis, G.V. (George), Pedersen, O. (Oluf), Froguel, P. (Philippe), Sunyer, J. (Jordi), Plomin, R. (Robert), Jacobsson, B. (Bo), Hansen, T. (Torben), Gonzalez, J.R. (Juan R.), Custovic, A. (Adnan), Raitakari, O.T. (Olli T.), Pennell, C.E. (Craig), Widén, E. (Elisabeth), Boomsma, D.I. (Dorret), Koppelman, G.H. (Gerard), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Hypponen, E. (Elina), McCarthy, M.I. (Mark), Lindi, V. (Virpi), Harri, N. (Niinikoski), Körner, A. (Antje), Bønnelykke, K. (Klaus), Heinrich, J. (Joachim), Melbye, M. (Mads), Rivadeneira Ramirez, F. (Fernando), Hakonarson, H. (Hakon), Ring, S.M. (Susan), Smith, A.V. (Davey), Sørensen, T.I.A. (Thorkild I.A.), Timpson, N.J. (Nicholas), Grant, S.F.A. (Struan), Jaddoe, V.W.V. (Vincent), Kalkwarf, H.J. (Heidi J.), Lappe, J.M. (Joan M.), Gilsanz, V. (Vicente), Oberfield, S.E. (Sharon E.), Shepherd, J.A. (John A.), and Kelly, A. (Andrea)

Abstract

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores.We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10-8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10-10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in streng

Published
2016
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12. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Author

Postmus, D. (Douwe), Trompet, S. (Stella), Deshmukh, H. (Harshal), Barnes, M.J. (Michael), Li, X. (Xiaohui), Warren, H. (Helen), Chasman, D.I. (Daniel), Zhou, K. (Kaixin), Arsenault, B.J. (Benoit J.), Donnelly, L.A. (Louise), Wiggins, K.L. (Kerri), Avery, C.L., Griffin, P. (Paula), Feng, Q. (Qiping), Taylor, K.D. (Kent), Li, G. (Guo), Evans, D.S. (Daniel), Smith, A.V. (Davey), Keyser, C.E. (Catherina Elisabeth) de, Johnson, A.D. (Andrew), Craen, A.J. (Anton) de, Stott, D.J. (David. J.), Buckley, B.M. (Brendan M.), Ford, I., Westendorp, R.G.J. (Rudi), Slagboom, P.E. (Eline), Sattar, N. (Naveed), Munroe, P. (Patricia), Sever, P. (Peter), Poulter, N.R. (Neil), Stanton, A. (Alice), Shields, D.C. (Denis C.), O'Brien, E. (Eoin), Shaw-Hawkins, S. (Sue), Chen, Y.-D.I. (Ida), Nickerson, D.A. (Deborah), Smith, J.D. (Joshua D.), Dubé, G.P. (Gregory), Boekholdt, S.M. (Matthijs), Hovingh, G.K. (Kees), Kastelein, J.J.P. (John), Mckeigue, P.M. (Paul), Betteridge, J. (John), Neil, A. (Andrew), Durrington, P.N. (Paul), Doney, A.S.F. (Alex), Carr, F. (Fiona), Morris, A.D. (Andrew), McCarthy, M.I. (Mark), Groop, L. (Leif), Ahlqvist, E. (Emma), Barroso, I.E. (Inês), Blackwell, K.L. (Kimberly), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panagiotis), Duncanson, A. (Audrey), Jankowski, J.A. (Janusz Antoni), Markus, H.S. (Hugh), Mathew, C.G. (Christopher G.), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Viswanathan, A.C. (Ananth), Wood, N.W. (Nicholas), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Donnelly, P. (Peter), Langford, C. (Cordelia), Hunt, S.E. (Sarah), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, M. (Matthew), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Smith, N.L. (Nicholas), Lumley, T. (Thomas), Whitsel, E.A. (Eric), Stürmer, T., Boerwinkle, E.A. (Eric), Ngwa, J.S., O'Donnell, C.J. (Christopher J.), Vasan, R.S. (Ramachandran Srini), Wei, W.-Q. (Wei-Qi), Wilke, R.A. (Russell A.), Liu, C.-T. (Ching-Ti), Sun, F. (Fangui), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Post, W. (Wendy), Sotoodehnia, N. (Nona), Arnold, A.M. (Alice), Stafford, J.M. (Jeanette M.), Ding, J. (Jingzhong), Herrington, D.M. (David), Kritchevsky, S.B. (Stephen), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Chu, A.Y. (Audrey), Giulianini, F. (Franco), MacFadyen, J.G. (Jean G.), Barratt, B.J. (Bryan J.), Nyberg, F. (Fredrik), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Emilsson, V. (Valur), Franco, O.H. (Oscar), Ridker, P.M. (Paul), Gudnason, V. (Vilmundur), Liu, Y. (YongMei), Denny, J.C. (Joshua C.), Ballantyne, C. (Christie), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), Psaty, B.M. (Bruce), Tardif, J.-C. (Jean-Claude), Colhoun, H.M. (H.), Hitman, G.A. (Graham), Krauss, R.M. (Ronald), Jukema, J.W. (Jan Wouter), Caulfield, M. (Mark), Postmus, D. (Douwe), Trompet, S. (Stella), Deshmukh, H. (Harshal), Barnes, M.J. (Michael), Li, X. (Xiaohui), Warren, H. (Helen), Chasman, D.I. (Daniel), Zhou, K. (Kaixin), Arsenault, B.J. (Benoit J.), Donnelly, L.A. (Louise), Wiggins, K.L. (Kerri), Avery, C.L., Griffin, P. (Paula), Feng, Q. (Qiping), Taylor, K.D. (Kent), Li, G. (Guo), Evans, D.S. (Daniel), Smith, A.V. (Davey), Keyser, C.E. (Catherina Elisabeth) de, Johnson, A.D. (Andrew), Craen, A.J. (Anton) de, Stott, D.J. (David. J.), Buckley, B.M. (Brendan M.), Ford, I., Westendorp, R.G.J. (Rudi), Slagboom, P.E. (Eline), Sattar, N. (Naveed), Munroe, P. (Patricia), Sever, P. (Peter), Poulter, N.R. (Neil), Stanton, A. (Alice), Shields, D.C. (Denis C.), O'Brien, E. (Eoin), Shaw-Hawkins, S. (Sue), Chen, Y.-D.I. (Ida), Nickerson, D.A. (Deborah), Smith, J.D. (Joshua D.), Dubé, G.P. (Gregory), Boekholdt, S.M. (Matthijs), Hovingh, G.K. (Kees), Kastelein, J.J.P. (John), Mckeigue, P.M. (Paul), Betteridge, J. (John), Neil, A. (Andrew), Durrington, P.N. (Paul), Doney, A.S.F. (Alex), Carr, F. (Fiona), Morris, A.D. (Andrew), McCarthy, M.I. (Mark), Groop, L. (Leif), Ahlqvist, E. (Emma), Barroso, I.E. (Inês), Blackwell, K.L. (Kimberly), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panagiotis), Duncanson, A. (Audrey), Jankowski, J.A. (Janusz Antoni), Markus, H.S. (Hugh), Mathew, C.G. (Christopher G.), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Viswanathan, A.C. (Ananth), Wood, N.W. (Nicholas), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Donnelly, P. (Peter), Langford, C. (Cordelia), Hunt, S.E. (Sarah), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, M. (Matthew), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Smith, N.L. (Nicholas), Lumley, T. (Thomas), Whitsel, E.A. (Eric), Stürmer, T., Boerwinkle, E.A. (Eric), Ngwa, J.S., O'Donnell, C.J. (Christopher J.), Vasan, R.S. (Ramachandran Srini), Wei, W.-Q. (Wei-Qi), Wilke, R.A. (Russell A.), Liu, C.-T. (Ching-Ti), Sun, F. (Fangui), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Post, W. (Wendy), Sotoodehnia, N. (Nona), Arnold, A.M. (Alice), Stafford, J.M. (Jeanette M.), Ding, J. (Jingzhong), Herrington, D.M. (David), Kritchevsky, S.B. (Stephen), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Chu, A.Y. (Audrey), Giulianini, F. (Franco), MacFadyen, J.G. (Jean G.), Barratt, B.J. (Bryan J.), Nyberg, F. (Fredrik), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Emilsson, V. (Valur), Franco, O.H. (Oscar), Ridker, P.M. (Paul), Gudnason, V. (Vilmundur), Liu, Y. (YongMei), Denny, J.C. (Joshua C.), Ballantyne, C. (Christie), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), Psaty, B.M. (Bruce), Tardif, J.-C. (Jean-Claude), Colhoun, H.M. (H.), Hitman, G.A. (Graham), Krauss, R.M. (Ronald), Jukema, J.W. (Jan Wouter), and Caulfield, M. (Mark)

Published
2014
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13. Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

Author

Benyamin, B. (Beben), Pourcain, B. (Bst), Davis, O.S.P. (Oliver S.), Davies, G. (Gail), Hansell, N.K. (Narelle), Brion, M.-J. (Maria), Kirkpatrick, R.M. (Robert), Cents, R.A.M. (Rolieke), Franić, S. (Sanja), Miller, M.B. (Michael), Haworth, C.M.A. (Claire), Meaburn, E.L. (Emma), Price, T.S. (Thomas), Evans, D.M. (David), Timpson, N.J. (Nicholas), Kemp, J.P. (John), Ring, S.M. (Susan), McArdle, W.L. (Wendy), Medland, S.E. (Sarah), Yang, J. (Jian), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Scheet, P. (Paul), Xiao, X. (Xiangjun), Hudziak, J.J. (James), Geus, E.J.C. (Eco) de, Jaddoe, V.W.V. (Vincent), Starr, J.M. (John), Verhulst, F.C. (Frank), Pennell, C.E. (Craig), Tiemeier, H.W. (Henning), Iacono, W.G. (William), Palmer, C. (Cameron), Montgomery, G.W. (Grant), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Posthuma, D. (Danielle), McGue, M. (Matt), Wright, M.J. (Margaret), Davey-Smith, G. (George), Deary, I.J. (Ian), Plomin, R. (Robert), Visscher, P.M. (Peter), Benyamin, B. (Beben), Pourcain, B. (Bst), Davis, O.S.P. (Oliver S.), Davies, G. (Gail), Hansell, N.K. (Narelle), Brion, M.-J. (Maria), Kirkpatrick, R.M. (Robert), Cents, R.A.M. (Rolieke), Franić, S. (Sanja), Miller, M.B. (Michael), Haworth, C.M.A. (Claire), Meaburn, E.L. (Emma), Price, T.S. (Thomas), Evans, D.M. (David), Timpson, N.J. (Nicholas), Kemp, J.P. (John), Ring, S.M. (Susan), McArdle, W.L. (Wendy), Medland, S.E. (Sarah), Yang, J. (Jian), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Scheet, P. (Paul), Xiao, X. (Xiangjun), Hudziak, J.J. (James), Geus, E.J.C. (Eco) de, Jaddoe, V.W.V. (Vincent), Starr, J.M. (John), Verhulst, F.C. (Frank), Pennell, C.E. (Craig), Tiemeier, H.W. (Henning), Iacono, W.G. (William), Palmer, C. (Cameron), Montgomery, G.W. (Grant), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Posthuma, D. (Danielle), McGue, M. (Matt), Wright, M.J. (Margaret), Davey-Smith, G. (George), Deary, I.J. (Ian), Plomin, R. (Robert), and Visscher, P.M. (Peter)

Abstract

Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17 989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10 -15, 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10 -5), 3.5% (P=10 -3) and 0.5% (P=6 × 10 -5) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.

Published
2014
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14. Common variation near ROBO2 is associated with expressive vocabulary in infancy

Author

St Pourcain, B. (Beate), Cents, R.A.M. (Rolieke), Whitehouse, A.J.O. (Andrew), Haworth, C.M.A. (Claire M.), Davis, O.S.P. (Oliver S.), O'Reilly, P.F. (Paul), Roulstone, S. (Susan), Wren, Y. (Yvonne), Ang, Q.W. (Qi W.), Velders, F.P. (Fleur), Evans, D.M. (David M.), Kemp, J.P. (John), Warrington, N.M. (Nicole), Miller, L. (Laura), Timpson, N.J. (Nicholas), Ring, S.M. (Susan), Verhulst, F.C. (Frank), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Meaburn, E.L. (Emma), Price, T.S. (Thomas), Dale, P.S. (Philip S.), Pillas, D. (Demetris), Yliherva, A. (Anneli), Rodriguez, A. (Alina), Golding, J. (Jean), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Plomin, R. (Robert), Pennell, C.E. (Craig), Tiemeier, H.W. (Henning), Smith, A.V. (Davey), St Pourcain, B. (Beate), Cents, R.A.M. (Rolieke), Whitehouse, A.J.O. (Andrew), Haworth, C.M.A. (Claire M.), Davis, O.S.P. (Oliver S.), O'Reilly, P.F. (Paul), Roulstone, S. (Susan), Wren, Y. (Yvonne), Ang, Q.W. (Qi W.), Velders, F.P. (Fleur), Evans, D.M. (David M.), Kemp, J.P. (John), Warrington, N.M. (Nicole), Miller, L. (Laura), Timpson, N.J. (Nicholas), Ring, S.M. (Susan), Verhulst, F.C. (Frank), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Meaburn, E.L. (Emma), Price, T.S. (Thomas), Dale, P.S. (Philip S.), Pillas, D. (Demetris), Yliherva, A. (Anneli), Rodriguez, A. (Alina), Golding, J. (Jean), Jaddoe, V.W.V. (Vincent), Jarvelin, M.-R. (Marjo-Riitta), Plomin, R. (Robert), Pennell, C.E. (Craig), Tiemeier, H.W. (Henning), and Smith, A.V. (Davey)

Abstract

Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15-18 months, 'one-word stage', NTotal=8,889) and a later (24-30 months, 'two-word stage', NTotal=10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P=1.3×10-8) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h15-18-months 2=0.13, meta-GCTA h24-30-months 2 =0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h24-months 2=0.20).

Published
2014
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15. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

Author

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

Abstract

We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.

Published
2014
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