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1. Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies

Author

Munn‐Chernoff, Melissa A, Johnson, Emma C, Chou, Yi‐Ling, Coleman, Jonathan RI, Thornton, Laura M, Walters, Raymond K, Yilmaz, Zeynep, Baker, Jessica H, Hübel, Christopher, Gordon, Scott, Medland, Sarah E, Watson, Hunna J, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti‐Rodríguez, Paola, Hanscombe, Ken B, Adan, Roger AH, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver SP, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak‐Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández‐Aranda, Fernando, Fichter, Manfred M, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J, Forzan, Monica, Franklin, Christopher S, Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G, Herms, Stefan, Herpertz‐Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M, Hudson, James I, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez‐Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien JH, Kennedy, James L, Keski‐Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl‐Ri, Klump, Kelly L, Knudsen, Gun Peggy S, and La Via, Maria C

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Epidemiology, Health Sciences, Psychology, Pharmacology and Pharmaceutical Sciences, Nutrition, Brain Disorders, Alcoholism, Alcohol Use and Health, Mental Health, Eating Disorders, Substance Misuse, Genetics, Tobacco Smoke and Health, Tobacco, Human Genome, Drug Abuse (NIDA only), Prevention, Clinical Research, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Good Health and Well Being, Alcoholism, Depressive Disorder, Major, Feeding and Eating Disorders, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Schizophrenia, Substance-Related Disorders, Tobacco Use Disorder, eating disorders, genetic correlation, substance use, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biomedical and clinical sciences, Health sciences
Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

Published
2021

2. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Author

Watson, Hunna J, Yilmaz, Zeynep, Thornton, Laura M, Hübel, Christopher, Coleman, Jonathan RI, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Medland, Sarah E, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Purves, Kirstin L, Adan, Roger AH, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Baker, Jessica H, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver SP, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J, Forzan, Monica, Franklin, Christopher S, Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M, Hudson, James I, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien JH, Kennedy, James L, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Klareskog, Lars, Klump, Kelly L, Knudsen, Gun Peggy S, La Via, Maria C, Le Hellard, Stephanie, and Levitan, Robert D

Subjects
Biological Sciences, Genetics, Anorexia, Serious Mental Illness, Nutrition, Prevention, Mental Health, Clinical Research, Human Genome, Brain Disorders, Pediatric, Eating Disorders, Mental health, Adult, Anorexia Nervosa, Body Mass Index, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Male, Mental Disorders, Metabolic Diseases, Phenotype, Prognosis, Quantitative Trait Loci, Anorexia Nervosa Genetics Initiative, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

Published
2019

3. Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Author

Rhodes, Christopher J, Batai, Ken, Bleda, Marta, Haimel, Matthias, Southgate, Laura, Germain, Marine, Pauciulo, Michael W, Hadinnapola, Charaka, Aman, Jurjan, Girerd, Barbara, Arora, Amit, Knight, Jo, Hanscombe, Ken B, Karnes, Jason H, Kaakinen, Marika, Gall, Henning, Ulrich, Anna, Harbaum, Lars, Cebola, Inês, Ferrer, Jorge, Lutz, Katie, Swietlik, Emilia M, Ahmad, Ferhaan, Amouyel, Philippe, Archer, Stephen L, Argula, Rahul, Austin, Eric D, Badesch, David, Bakshi, Sahil, Barnett, Christopher, Benza, Raymond, Bhatt, Nitin, Bogaard, Harm J, Burger, Charles D, Chakinala, Murali, Church, Colin, Coghlan, John G, Condliffe, Robin, Corris, Paul A, Danesino, Cesare, Debette, Stéphanie, Elliott, C Gregory, Elwing, Jean, Eyries, Melanie, Fortin, Terry, Franke, Andre, Frantz, Robert P, Frost, Adaani, Garcia, Joe GN, Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Gibbs, J Simon R, Harley, John, He, Hua, Hill, Nicholas S, Hirsch, Russel, Houweling, Arjan C, Howard, Luke S, Ivy, Dunbar, Kiely, David G, Klinger, James, Kovacs, Gabor, Lahm, Tim, Laudes, Matthias, Machado, Rajiv D, Ross, Robert V MacKenzie, Marsolo, Keith, Martin, Lisa J, Moledina, Shahin, Montani, David, Nathan, Steven D, Newnham, Michael, Olschewski, Andrea, Olschewski, Horst, Oudiz, Ronald J, Ouwehand, Willem H, Peacock, Andrew J, Pepke-Zaba, Joanna, Rehman, Zia, Robbins, Ivan, Roden, Dan M, Rosenzweig, Erika B, Saydain, Ghulam, Scelsi, Laura, Schilz, Robert, Seeger, Werner, Shaffer, Christian M, Simms, Robert W, Simon, Marc, Sitbon, Olivier, Suntharalingam, Jay, Tang, Haiyang, Tchourbanov, Alexander Y, Thenappan, Thenappan, Torres, Fernando, Toshner, Mark R, Treacy, Carmen M, Noordegraaf, Anton Vonk, Waisfisz, Quinten, and Walsworth, Anna K

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Genetics, Human Genome, Lung, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotyping Techniques, HLA-DP alpha-Chains, HLA-DP beta-Chains, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Pulmonary Arterial Hypertension, Risk Assessment, SOXF Transcription Factors, Signal Transduction, Survival Analysis, UK NIHR BioResource Rare Diseases Consortium, UK PAH Cohort Study Consortium, US PAH Biobank Consortium, Public Health and Health Services, Other Medical and Health Sciences, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundRare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.MethodsWe did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.FindingsA locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity.InterpretationThis is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials.FundingUK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR.

Published
2019

6. Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

Author

Wray, Naomi R., Ripke, Stephan, 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, Deary, Ian J., 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., 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, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, 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, Andrés G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., 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, EJC., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela AF., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M., O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Rietschel, Marcella, 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., Glanville, Kylie P., Hanscombe, Ken B., Euesden, Jack, Choi, Shing Wan, Purves, Kirstin L., Blackwood, Douglas H.R., and de Geus, Eco J.C.

Published
2020
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10. Why Do Spatial Abilities Predict Mathematical Performance?

Author

Tosto, Maria Grazia, Hanscombe, Ken B., and Haworth, Claire M. A.

Abstract

Spatial ability predicts performance in mathematics and eventual expertise in science, technology and engineering. Spatial skills have also been shown to rely on neuronal networks partially shared with mathematics. Understanding the nature of this association can inform educational practices and intervention for mathematical underperformance. Using data on two aspects of spatial ability and three domains of mathematical ability from 4174 pairs of 12-year-old twins, we examined the relative genetic and environmental contributions to variation in spatial ability and to its relationship with different aspects of mathematics. Environmental effects explained most of the variation in spatial ability (~70%) and in mathematical ability (~60%) at this age, and the effects were the same for boys and girls. Genetic factors explained about 60% of the observed relationship between spatial ability and mathematics, with a substantial portion of the relationship explained by common environmental influences (26% and 14% by shared and non-shared environments respectively). These findings call for further research aimed at identifying specific environmental mediators of the spatial-mathematics relationship.

Published
2014
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11. Genome-Wide Association Study of Receptive Language Ability of 12-Year-Olds

Author

Harlaar, Nicole, Meaburn, Emma L., Hayiou-Thomas, Marianna E., Davis, Oliver S. P., Docherty, Sophia, Hanscombe, Ken B., Haworth, Claire M. A., Price, Thomas S., Trzaskowski, Maciej, Dale, Philip S., and Plomin, Robert

Abstract

Purpose: Researchers have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. In the current study, the authors attempted to identify some of the genes responsible for the heritability of receptive language ability using a "genome-wide association" approach. Method: The authors administered 4 Internet-based measures of receptive language (vocabulary, semantics, syntax, and pragmatics) to a sample of 2,329 twelve-year-olds for whom DNA and genome-wide genotyping were available. Nearly 700,000 single-nucleotide polymorphisms (SNPs) and 1 million imputed SNPs were included in a genome-wide association analysis of receptive language composite scores. Results: No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome ( p < 5 × 10[superscript -8]). The strongest SNP association did not replicate in an additional sample of 2,639 twelve-year-olds. Conclusions: These results indicate that individual differences in receptive language ability in the general population do not reflect common genetic variants that account for more than 3% of the phenotypic variance. The search for genetic variants associated with language skill will require larger samples and additional methods to identify and functionally characterize the full spectrum of risk variants.

Published
2014
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12. Understanding the Science-Learning Environment: A Genetically Sensitive Approach

Author

Haworth, Claire M. A., Davis, Oliver S. P., Hanscombe, Ken B., Kovas, Yulia, Dale, Philip S., and Plomin, Robert

Abstract

Previous studies have shown that environmental influences on school science performance increase in importance from primary to secondary school. Here we assess for the first time the relationship between the science-learning environment and science performance using a genetically sensitive approach to investigate the aetiology of this link. 3000 pairs of 14-year-old twins from the UK Twins Early Development Study reported on their experiences of the science-learning environment and were assessed for their performance in science using a web-based test of scientific enquiry. Multivariate twin analyses were used to investigate the genetic and environmental links between environment and outcome. The most surprising result was that the science-learning environment was almost as heritable (43%) as performance on the science test (50%), and showed negligible shared environmental influence (3%). Genetic links explained most (56%) of the association between learning environment and science outcome, indicating gene-environment correlation. (Contains 4 tables and 1 figure.)

Published
2013
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13. Chaotic Homes and School Achievement: A Twin Study

Author

Hanscombe, Ken B., Haworth, Claire M. A., and Davis, Oliver S. P.

Abstract

Background: Chaotic homes predict poor school performance. Given that it is known that genes affect both children's experience of household chaos and their school achievement, to what extent is the relationship between high levels of noise and environmental confusion in the home, and children's school performance, mediated by heritable child effects? This is the first study to explore the genetic and environmental pathways between household chaos and academic performance. Method: Children's perceptions of family chaos at ages 9 and 12 and their school performance at age 12 were assessed in more than 2,300 twin pairs. The use of child-specific measures in a multivariate genetic analysis made it possible to investigate the genetic and environmental origins of the covariation between children's experience of chaos in the home and their school achievement. Results: Children's experience of family chaos and their school achievement were significantly correlated in the expected negative direction (r = -0.26). As expected, shared environmental factors explained a large proportion (63%) of the association. However, genetic factors accounted for a significant proportion (37%) of the association between children's experience of household chaos and their school performance. Conclusions: The association between chaotic homes and poor performance in school, previously assumed to be entirely environmental in origin, is in fact partly genetic. How children's home environment affects their academic achievement is not simply in the direction environment [right arrow] child [right arrow] outcome. Instead, genetic factors that influence children's experience of the disordered home environment also affect how well they do at school. The relationship between the child, their environment and their performance at school is complex: both genetic and environmental factors play a role. (Contains 1 figure and 4 tables.)

Published
2011
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14. The Nature (and Nurture) of Children's Perceptions of Family Chaos

Author

Hanscombe, Ken B., Haworth, Claire M. A., and Davis, Oliver S. P.

Abstract

Chaos in the home is a key environment in cognitive and behavioural development. However, we show that children's experience of home chaos is partly genetically mediated. We assessed children's perceptions of household chaos at ages 9 and 12 in 2337 pairs of twins. Using child-specific reports allowed us to use structural equation modelling to explore the genetic and environmental etiologies of children's perceptions of chaos. We found that these perceptions are significantly heritable (22%), with the remainder explained by environmental influences. Finding that genes influence children's experience of chaotic environments has far-reaching implications for how we conceptualize the family home and its impact on cognitive and behavioural development. (Contains 3 tables.)

Published
2010
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15. In Search of Genes Associated with Risk for Psychopathic Tendencies in Children: A Two-Stage Genome-Wide Association Study of Pooled DNA

Author

Viding, Essi, Hanscombe, Ken B., Curtis, Charles J. C., Davis, Oliver S. P., Meaburn, Emma L., and Plomin, Robert

Abstract

Background: Quantitative genetic data from our group indicates that antisocial behaviour (AB) is strongly heritable when coupled with psychopathic, callous-unemotional (CU) personality traits. We have also demonstrated that the genetic influences for AB and CU overlap considerably. We conducted a genome-wide association scan that capitalises on these findings in an attempt to identify quantitative trait loci (QTLs) that may increase risk for psychopathic tendencies (AB+/CU+). Methods: Teacher ratings at age 7 were used to screen 8374 twins with available DNA samples for individuals that were high vs. low on both AB and CU. In Stage 1, we screened for allele frequency differences in 642,432 autosomal single-nucleotide polymorphisms (SNPs) using the Affymetrix 6.0 GeneChip with pooled DNA for high-scoring (AB+/CU+) versus low-scoring children (N = 300/group). In Stage 2, we tested the 3000 most strongly associated SNPs from Stage 1 for association in the same direction in a second sample of high- versus low-scoring children from the same twin study (18% co-twins). Results: Using allele frequencies estimated from pooled DNA, we found suggestive evidence for enrichment of association in the second stage of our two-stage genome-wide association design and focus on reporting the 30 top-ranking SNPs nominally associated with psychopathic tendencies. These SNPs include neurodevelopmental genes such as ROBO2. Conclusions: Although none of the SNPs reached genome-wide statistical significance we have generated a list of SNPs that are potentially associated with psychopathic tendencies, which we believe warrant verification and replication in large independent and clinical samples.

Published
2010
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16. Genetic variation at 16q24.2 is associated with small vessel stroke

Author

Traylor, Matthew, Malik, Rainer, Nalls, Mike A., Cotlarciuc, Ioana, Radmanesh, Farid, Thorleifsson, Gudmar, Hanscombe, Ken B., Langefeld, Carl, Saleheen, Danish, Rost, Natalia S., Yet, Idil, Spector, Tim D., Bell, Jordana T., Hannon, Eilis, Mill, Jonathan, Chauhan, Ganesh, Debette, Stephanie, Bis, Joshua C., Longstreth, W.T., Jr., Ikram, M. Arfan, Launer, Lenore J., Seshadri, Sudha, Hamilton‐Bruce, Monica Anne, Jimenez‐Conde, Jordi, Cole, John W., Schmidt, Reinhold, Słowik, Agnieszka, Lemmens, Robin, Lindgren, Arne, Melander, Olle, Grewal, Raji P., Sacco, Ralph L., Rundek, Tatjana, Rexrode, Kathryn, Arnett, Donna K., Johnson, Julie A., Benavente, Oscar R., Wasssertheil‐Smoller, Sylvia, Lee, Jin‐Moo, Pulit, Sara L., Wong, Quenna, Rich, Stephen S., de Bakker, Paul I.W., McArdle, Patrick F., Woo, Daniel, Anderson, Christopher D., Xu, Huichun, Heitsch, Laura, Fornage, Myriam, Jern, Christina, Stefansson, Kari, Thorsteinsdottir, Unnur, Gretarsdottir, Solveig, Lewis, Cathryn M., Sharma, Pankaj, Sudlow, Cathie L.M., Rothwell, Peter M., Boncoraglio, Giorgio B., Thijs, Vincent, Levi, Chris, Meschia, James F., Rosand, Jonathan, Kittner, Steven J., Mitchell, Braxton D., Dichgans, Martin, Worrall, Bradford B., and Markus, Hugh S.

Published
2017
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20. Genome-wide association study of MRI markers of cerebral small vessel disease in 42,310 participants

Author

Persyn, Elodie, Hanscombe, Ken B., Howson, Joanna M. M., Lewis, Cathryn M., Traylor, Matthew, and Markus, Hugh S.

Subjects
141, 631/208/205/2138, 692/617/375/1370, 45/43, article, 631/378/2583
Abstract

Cerebral small vessel disease is a major cause of stroke and dementia, but its genetic basis is incompletely understood. We perform a genetic study of three MRI markers of the disease in UK Biobank imaging data and other sources: white matter hyperintensities (N = 42,310), fractional anisotropy (N = 17,663) and mean diffusivity (N = 17,467). Our aim is to better understand the disease pathophysiology. Across the three traits, we identify 31 loci, of which 21 were previously unreported. We perform a transcriptome-wide association study to identify associations with gene expression in relevant tissues, identifying 66 associated genes across the three traits. This genetic study provides insights into the understanding of the biological mechanisms underlying small vessel disease.

Published
2021
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22. Additional file 1 of The genetic case for cardiorespiratory fitness as a clinical vital sign and the routine prescription of physical activity in healthcare

Author

Hanscombe, Ken B., Persyn, Elodie, Traylor, Matthew, Glanville, Kylie P., Hamer, Mark, Coleman, Jonathan R. I., and Lewis, Cathryn M.

Abstract

Additional file 1:. Supplementary Methods (genetic data quality control, GWAS considerations, alternate genetic association models, and post GWAS details), Results (including alternate association models, GWAS post-processing), Tables S1 ��� S9, and Figures S1 ��� S52.

Published
2021
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23. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

Munn-Chernoff, Melissa A, Johnson, Emma C, Chou, Yi-Ling, Coleman, Jonathan RI, Thornton, Laura M, Walters, Raymond K, Yilmaz, Zeynep, Baker, Jessica H, Hübel, Christopher, Gordon, Scott, Medland, Sarah E, Watson, Hunna J, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Adan, Roger AH, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver SP, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J, Forzan, Monica, Franklin, Christopher S, Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos Mayora, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M, Hudson, James I, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien JH, Kennedy, James L, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Klump, Kelly L, Knudsen, Gun Peggy S, and La Via, Maria C

Subjects
Drug Abuse (NIDA Only), Substance-Related Disorders, Eating Disorders, substance use, Medical and Health Sciences, Linkage Disequilibrium, Feeding and Eating Disorders, Substance Misuse, Alcohol Use and Health, Risk Factors, Clinical Research, 2.3 Psychological, mental disorders, Tobacco, Genetics, Humans, 2.1 Biological and endogenous factors, Aetiology, Polymorphism, Nutrition, Depressive Disorder, Tobacco Smoke and Health, Prevention, Human Genome, Psychology and Cognitive Sciences, Substance Abuse, Major, Tobacco Use Disorder, Single Nucleotide, genetic correlation, Brain Disorders, Alcoholism, Good Health and Well Being, Phenotype, Mental Health, Schizophrenia, social and economic factors, Genome-Wide Association Study
Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

Published
2021

24. Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression

Author

Glanville, Kylie P, Coleman, Jonathan R I, Binder, Elisabeth B, 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, Blackwood, Douglas H R, 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, Boomsma, Dorret I, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A, MacIntyre, Donald J, MacKinnon, Dean F, Maier, Robert M, Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, Buttenschøn, Henriette N, McGuffin, Peter, Medland, Sarah E, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M, Montgomery, Grant W, Mostafavi, Sara, Colodro-Conde, Lucía, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, O'Reilly, Paul F, Oskarsson, Hogni, Owen, Michael J, Painter, Jodie N, Pedersen, Carsten Bøcker, Dannlowski, Udo, Pedersen, Marianne Giørtz, Peterson, Roseann E, Pettersson, Erik, Peyrot, Wouter J, Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A, Qvist, Per, Rice, John P, Riley, Brien P, Direk, Nese, 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, Dunn, Erin C, Smith, Daniel J, Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A, Forstner, Andreas J, Thorgeirsson, Thorgeir E, Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andrés G, Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M, Viktorin, Alexander, Visscher, Peter M, de Geus, Eco J C, Wang, Yunpeng, Webb, Bradley T, Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H, Wu, Yang, Xi, Hualin S, Yang, Jian, Zhang, Futao, Hanscombe, Ken B, Grabe, Hans J, Arolt, Volker, Baune, Bernhard T, Berger, Klaus, Cichon, Sven, de Geus, E. J. C., DePaulo, J Raymond, Domenici, Enrico, Domschke, Katharina, Hamilton, Steven P, Esko, Tõnu, Hayward, Caroline, Heath, Andrew C, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S, Lucae, Susanne, Madden, Pamela Af, Magnusson, Patrik K, Martin, Nicholas G, McIntosh, Andrew M, Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M, O'Donovan, Michael C, Paciga, Sara A, Pedersen, Nancy L, Penninx, Brenda W J H, Perlis, Roy H, Porteous, David J, Potash, James B, Preisig, Martin, Rietschel, Marcella, 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, Euesden, Jack, Choi, Shing Wan, Ripke, Stephan, Purves, Kirstin L, Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics, 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, Bryois, Julien, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E, Davies, Gail, Deary, Ian J, Degenhardt, Franziska, Derks, Eske M, Dolan, Conor V, Eley, Thalia C, Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K, Foo, Jerome C, Frank, Josef, Gaspar, Héléna A, Gill, Michael, Goes, Fernando S, Gordon, Scott D, Grove, Jakob, Adult Psychiatry, APH - Mental Health, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Wray, N.R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E.M., Abdellaoui, A., Adams, M.J., Agerbo, E., Air, T.M., Andlauer, TFM, Bacanu, S.A., Bækvad-Hansen, M., Beekman, ATF, Bigdeli, T.B., Binder, E.B., Bryois, J., Buttenschøn, H.N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J.H., Clarke, T.K., Coleman, JRI, Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G.E., Davies, G., Deary, I.J., Degenhardt, F., Derks, E.M., Direk, N., Dolan, C.V., Dunn, E.C., Eley, T.C., Escott-Price, V., Hassan Kiadeh, F.F., Finucane, H.K., Foo, J.C., Forstner, A.J., Frank, J., Gaspar, H.A., Gill, M., Goes, F.S., Gordon, S.D., Grove, J., Hall, L.S., Hansen, C.S., Hansen, T.F., Herms, S., Hickie, I.B., Hoffmann, P., Homuth, G., Horn, C., Hottenga, J.J., Hougaard, D.M., Howard, D.M., Ising, M., Jansen, R., Jones, I., Jones, L.A., 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., McGrath, P., McGuffin, P., Medland, S.E., Mehta, D., Middeldorp, C.M., Mihailov, E., Milaneschi, Y., Milani, L., Mondimore, F.M., Montgomery, G.W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M.G., Nyholt, D.R., O'Reilly, P.F., Oskarsson, H., Owen, M.J., Painter, J.N., Pedersen, C.B., Pedersen, M.G., Peterson, R.E., Pettersson, E., Peyrot, W.J., Pistis, G., Posthuma, D., Quiroz, J.A., Qvist, P., Rice, J.P., Riley, B.P., Rivera, M., Mirza, S.S., Schoevers, R., Schulte, E.C., Shen, L., Shi, J., Shyn, S.I., Sigurdsson, E., Sinnamon, GCB, 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., Van der Auwera, S., van Hemert, A.M., Viktorin, A., Visscher, P.M., Wang, Y., Webb, B.T., Weinsheimer, S.M., Wellmann, J., Willemsen, G., Witt, S.H., Wu, Y., Xi, H.S., Yang, J., Zhang, F., Arolt, V., Baune, B.T., Berger, K., Boomsma, D.I., Cichon, S., Dannlowski, U., de Geus, E., DePaulo, J.R., Domenici, E., Domschke, K., Esko, T., Grabe, H.J., Hamilton, S.P., Hayward, C., Heath, A.C., Kendler, K.S., Kloiber, S., Lewis, G., Li, Q.S., Lucae, S., Madden, P.A., Magnusson, P.K., Martin, N.G., McIntosh, A.M., Metspalu, A., Mors, O., Mortensen, P.B., Müller-Myhsok, B., Nordentoft, M., Nöthen, M.M., O'Donovan, M.C., Paciga, S.A., Pedersen, N.L., Penninx, BWJH, Perlis, R.H., Porteous, D.J., Potash, J.B., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T.G., Smoller, J.W., Stefansson, K., Tiemeier, H., Uher, R., Völzke, H., Weissman, M.M., Werge, T., Lewis, C.M., Levinson, D.F., Breen, G., Børglum, A.D., Sullivan, P.F., Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, APH - Methodology, Functional Genomics, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, Epidemiology, Child and Adolescent Psychiatry / Psychology, Psychiatry, Internal Medicine, Human genetics, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Perceptual and Cognitive Neuroscience (PCN)

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Major histocompatibility complex, LOCI, Complement, Autoimmune disorder, Genome-wide association study, Human leukocyte antigen, Genetic association, Major depressive disorder, Article, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, HLA Antigens, Genetic predisposition, IMPUTATION, Humans, ANXIETY, Genetic Predisposition to Disease, ddc:610, GENOME-WIDE ASSOCIATION, AUTOIMMUNE-DISEASE, Biological Psychiatry, Alleles, Complement component 4, Depressive Disorder, Major, Major histoconnpatibility complex, COMPLEX, biology, Depression, Haplotype, Odds ratio, ddc, 3. Good health, 030104 developmental biology, Haplotypes, Immunology, biology.protein, RISK-FACTORS, INFERENCE, HEALTH, 030217 neurology & neurosurgery
Abstract

Background\ud \ud The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression.\ud \ud \ud Methods\ud \ud We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4).\ud \ud \ud Results\ud \ud No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99).\ud \ud \ud Conclusions\ud \ud We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

Published
2020

25. Classical Human Leukocyte Antigen Alleles And C4 Haplotypes Are Not Significantly Associated With Depression

Author

Glanville, Kylie P., Coleman, Jonathan R.I., Hanscombe, Ken B., Euesden, Jack, Choi, Shing Wan, Purves, Kirstin L., Breen, Gerome, Air, Tracy M., Andlauer, Till F.M., Baune, Bernhard T., Binder, Elisabeth B., Blackwood, Douglas H.R., Boomsma, Dorret I., Buttenschøn, Henriette N., Colodro-Conde, Lucía, Dannlowski, Udo, Direk, Nese, Dunn, Erin C., Forstner, Andreas J., de Geus, Eco J.C., Grabe, Hans J., Hamilton, Steven P., Jones, Ian, Jones, Lisa A., Knowles, James A., Kutalik, Zoltán, Levinson, Douglas F., Lewis, Glyn, Lind, Penelope A., Lucae, Susanne, Magnusson, Patrik K., McGuffin, Peter, McIntosh, Andrew M., Milaneschi, Yuri, Mors, Ole, Mostafavi, Sara, Müller-Myhsok, Bertram, Pedersen, Nancy L., Penninx, Brenda W.J.H., Potash, James B., Preisig, Martin, Ripke, Stephan, Shi, Jianxin, Shyn, Stanley I., Smoller, Jordan W., Streit, Fabian, Sullivan, Patrick F., Tiemeier, Henning, Uher, Rudolf, Van der Auwera, Sandra, Weissman, Myrna M., O'Reilly, Paul F., Lewis, Cathryn M., Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Bryois, Julien, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Dolan, Conor V., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., and Foo, Jerome C.

Published
2020
Full Text
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26. Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

Author

Munn-Chernoff, Melissa A., Johnson, Emma C., Chou, Yi Ling, Coleman, Jonathan R.I., Thornton, Laura M., Walters, Raymond K., Yilmaz, Zeynep, Baker, Jessica H., Hübel, Christopher, Gordon, Scott, Medland, Sarah E., Watson, Hunna J., Gaspar, Héléna A., Bryois, Julien, Hinney, Anke, Leppä, Virpi M., Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B., Adan, Roger A.H., Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A., Berrettini, Wade H., Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, 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., Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E., Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J., Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos Mayora, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G., Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J.H., Kennedy, James L., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl Ri, Klump, Kelly L., Knudsen, Gun Peggy S., La Via, Maria C., Le Hellard, Stephanie, Levitan, Robert D., Li, Dong, Lilenfeld, Lisa, Lin, Bochao Danae, Lissowska, Jolanta, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, McGuffin, Peter, Metspalu, Andres, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, Karen, Monteleone, Alessio Maria, Monteleone, Palmiero, Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, O'Toole, Julie K., Ophoff, Roel A., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Pinto, Dalila, Rabionet, Raquel, Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, 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, Sorbi, Sandro, Świątkowska, Beata, Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wagner, Gudrun, Walton, Esther, Widen, Elisabeth, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Bergen, Andrew W., Boden, Joseph M., Brandt, Harry, Crawford, Steven, Halmi, Katherine A., Horwood, L. John, Johnson, Craig, Kaplan, Allan S., Kaye, Walter H., Mitchell, James, Olsen, Catherine M., Pearson, John F., Pedersen, Nancy L., Strober, Michael, Werge, Thomas, Whiteman, David C., Woodside, D. Blake, Grove, Jakob, Henders, Anjali K., Larsen, Janne T., Parker, Richard, Petersen, Liselotte V., Jordan, Jennifer, Kennedy, Martin A., Birgegård, Andreas, Lichtenstein, Paul, Norring, Claes, Landén, Mikael, Mortensen, Preben Bo, Polimanti, Renato, McClintick, Jeanette N., Adkins, Amy E., Aliev, Fazil, Bacanu, Silviu Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna M., Bigdeli, Tim B., Chen, Li Shiun, Clarke, Toni Kim, Degenhardt, Franziska, Docherty, Anna R., Edwards, Alexis C., Foo, Jerome C., Fox, Louis, Frank, Josef, Hack, Laura M., Hartmann, Annette M., Hartz, Sarah M., Heilmann-Heimbach, Stefanie, Hodgkinson, Colin, Hoffmann, Per, Hottenga, Jouke Jan, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion S., Mbarek, Hamdi, McIntosh, Andrew M., McQueen, Matthew B., Meyers, Jacquelyn L., Milaneschi, Yuri, Palviainen, Teemu, Peterson, Roseann E., Ryu, Euijung, Saccone, Nancy L., Salvatore, Jessica E., Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen Chyong, Webb, Bradley T., Wedow, Robbee, Wetherill, Leah, Wills, Amanda G., Zhou, Hang, Boardman, Jason D., Chen, Danfeng, Choi, Doo Sup, Copeland, William E., Culverhouse, Robert C., Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin W., Frye, Mark A., Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Koller, Gabriele, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael T., Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison D., Nurnberger, John I., Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen D., Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc A., Soyka, Michael, Treutlein, Jens, Witt, Stephanie H., Wodarz, Norbert, Zill, Peter, Adkins, Daniel E., Boomsma, Dorret I., Bierut, Laura J., Brown, Sandra A., Bucholz, Kathleen K., Costello, E. Jane, de Wit, Harriet, Diazgranados, Nancy, Eriksson, Johan G., Farrer, Lindsay A., Foroud, Tatiana M., Gillespie, Nathan A., Goate, Alison M., Goldman, David, Grucza, Richard A., Hancock, Dana B., Harris, Kathleen Mullan, Hesselbrock, Victor, Hewitt, John K., Hopfer, Christian J., Iacono, William G., Johnson, Eric O., Karpyak, Victor M., Kendler, Kenneth S., Kranzler, Henry R., Krauter, Kenneth, Lind, Penelope A., McGue, Matt, MacKillop, James, Madden, Pamela A.F., Maes, Hermine H., Magnusson, Patrik K.E., Nelson, Elliot C., Nöthen, Markus M., Palmer, Abraham A., Penninx, Brenda W.J.H., Porjesz, Bernice, Rice, John P., Rietschel, Marcella, Riley, Brien P., Rose, Richard J., Shen, Pei Hong, Silberg, Judy, Stallings, Michael C., Tarter, Ralph E., Vanyukov, Michael M., Vrieze, Scott, Wall, Tamara L., Whitfield, John B., Zhao, Hongyu, Neale, Benjamin M., Wade, Tracey D., Heath, Andrew C., Montgomery, Grant W., Martin, Nicholas G., Sullivan, Patrick F., Kaprio, Jaakko, Breen, Gerome, Gelernter, Joel, Edenberg, Howard J., Bulik, Cynthia M., Agrawal, Arpana, Munn-Chernoff, Melissa A., Johnson, Emma C., Chou, Yi Ling, Coleman, Jonathan R.I., Thornton, Laura M., Walters, Raymond K., Yilmaz, Zeynep, Baker, Jessica H., Hübel, Christopher, Gordon, Scott, Medland, Sarah E., Watson, Hunna J., Gaspar, Héléna A., Bryois, Julien, Hinney, Anke, Leppä, Virpi M., Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B., Adan, Roger A.H., Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A., Berrettini, Wade H., Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, 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., Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E., Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J., Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos Mayora, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G., Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J.H., Kennedy, James L., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl Ri, Klump, Kelly L., Knudsen, Gun Peggy S., La Via, Maria C., Le Hellard, Stephanie, Levitan, Robert D., Li, Dong, Lilenfeld, Lisa, Lin, Bochao Danae, Lissowska, Jolanta, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, McGuffin, Peter, Metspalu, Andres, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, Karen, Monteleone, Alessio Maria, Monteleone, Palmiero, Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, O'Toole, Julie K., Ophoff, Roel A., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Pinto, Dalila, Rabionet, Raquel, Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, 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, Sorbi, Sandro, Świątkowska, Beata, Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wagner, Gudrun, Walton, Esther, Widen, Elisabeth, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Bergen, Andrew W., Boden, Joseph M., Brandt, Harry, Crawford, Steven, Halmi, Katherine A., Horwood, L. John, Johnson, Craig, Kaplan, Allan S., Kaye, Walter H., Mitchell, James, Olsen, Catherine M., Pearson, John F., Pedersen, Nancy L., Strober, Michael, Werge, Thomas, Whiteman, David C., Woodside, D. Blake, Grove, Jakob, Henders, Anjali K., Larsen, Janne T., Parker, Richard, Petersen, Liselotte V., Jordan, Jennifer, Kennedy, Martin A., Birgegård, Andreas, Lichtenstein, Paul, Norring, Claes, Landén, Mikael, Mortensen, Preben Bo, Polimanti, Renato, McClintick, Jeanette N., Adkins, Amy E., Aliev, Fazil, Bacanu, Silviu Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna M., Bigdeli, Tim B., Chen, Li Shiun, Clarke, Toni Kim, Degenhardt, Franziska, Docherty, Anna R., Edwards, Alexis C., Foo, Jerome C., Fox, Louis, Frank, Josef, Hack, Laura M., Hartmann, Annette M., Hartz, Sarah M., Heilmann-Heimbach, Stefanie, Hodgkinson, Colin, Hoffmann, Per, Hottenga, Jouke Jan, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion S., Mbarek, Hamdi, McIntosh, Andrew M., McQueen, Matthew B., Meyers, Jacquelyn L., Milaneschi, Yuri, Palviainen, Teemu, Peterson, Roseann E., Ryu, Euijung, Saccone, Nancy L., Salvatore, Jessica E., Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen Chyong, Webb, Bradley T., Wedow, Robbee, Wetherill, Leah, Wills, Amanda G., Zhou, Hang, Boardman, Jason D., Chen, Danfeng, Choi, Doo Sup, Copeland, William E., Culverhouse, Robert C., Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin W., Frye, Mark A., Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Koller, Gabriele, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael T., Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison D., Nurnberger, John I., Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen D., Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc A., Soyka, Michael, Treutlein, Jens, Witt, Stephanie H., Wodarz, Norbert, Zill, Peter, Adkins, Daniel E., Boomsma, Dorret I., Bierut, Laura J., Brown, Sandra A., Bucholz, Kathleen K., Costello, E. Jane, de Wit, Harriet, Diazgranados, Nancy, Eriksson, Johan G., Farrer, Lindsay A., Foroud, Tatiana M., Gillespie, Nathan A., Goate, Alison M., Goldman, David, Grucza, Richard A., Hancock, Dana B., Harris, Kathleen Mullan, Hesselbrock, Victor, Hewitt, John K., Hopfer, Christian J., Iacono, William G., Johnson, Eric O., Karpyak, Victor M., Kendler, Kenneth S., Kranzler, Henry R., Krauter, Kenneth, Lind, Penelope A., McGue, Matt, MacKillop, James, Madden, Pamela A.F., Maes, Hermine H., Magnusson, Patrik K.E., Nelson, Elliot C., Nöthen, Markus M., Palmer, Abraham A., Penninx, Brenda W.J.H., Porjesz, Bernice, Rice, John P., Rietschel, Marcella, Riley, Brien P., Rose, Richard J., Shen, Pei Hong, Silberg, Judy, Stallings, Michael C., Tarter, Ralph E., Vanyukov, Michael M., Vrieze, Scott, Wall, Tamara L., Whitfield, John B., Zhao, Hongyu, Neale, Benjamin M., Wade, Tracey D., Heath, Andrew C., Montgomery, Grant W., Martin, Nicholas G., Sullivan, Patrick F., Kaprio, Jaakko, Breen, Gerome, Gelernter, Joel, Edenberg, Howard J., Bulik, Cynthia M., and Agrawal, Arpana

Abstract

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotyp

Published
2020

30. Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts

Author

Fabbri, Chiara, primary, Hagenaars, Saskia P., additional, John, Catherine, additional, Williams, Alexander T., additional, Shrine, Nick, additional, Moles, Louise, additional, Hanscombe, Ken B., additional, Serretti, Alessandro, additional, Shepherd, David J., additional, Free, Robert S., additional, Wain, Louise V., additional, Tobin, Martin D., additional, and Lewis, Cathryn M., additional

Published
2020
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31. Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies

Author

Munn‐Chernoff, Melissa A., primary, Johnson, Emma C., additional, Chou, Yi‐Ling, additional, Coleman, Jonathan R.I., additional, Thornton, Laura M., additional, Walters, Raymond K., additional, Yilmaz, Zeynep, additional, Baker, Jessica H., additional, Hübel, Christopher, additional, Gordon, Scott, additional, Medland, Sarah E., additional, Watson, Hunna J., additional, Gaspar, Héléna A., additional, Bryois, Julien, additional, Hinney, Anke, additional, Leppä, Virpi M., additional, Mattheisen, Manuel, additional, Ripke, Stephan, additional, Yao, Shuyang, additional, Giusti‐Rodríguez, Paola, additional, Hanscombe, Ken B., additional, Adan, Roger A.H., additional, Alfredsson, Lars, additional, Ando, Tetsuya, additional, Andreassen, Ole A., additional, Berrettini, Wade H., additional, Boehm, Ilka, additional, Boni, Claudette, additional, Boraska Perica, Vesna, additional, Buehren, Katharina, additional, Burghardt, Roland, additional, Cassina, Matteo, additional, Cichon, Sven, additional, Clementi, Maurizio, additional, Cone, Roger D., additional, Courtet, Philippe, additional, Crow, Scott, additional, Crowley, James J., additional, Danner, Unna N., additional, Davis, Oliver S.P., additional, de Zwaan, Martina, additional, Dedoussis, George, additional, Degortes, Daniela, additional, DeSocio, Janiece E., additional, Dick, Danielle M., additional, Dikeos, Dimitris, additional, Dina, Christian, additional, Dmitrzak‐Weglarz, Monika, additional, Docampo, Elisa, additional, Duncan, Laramie E., additional, Egberts, Karin, additional, Ehrlich, Stefan, additional, Escaramís, Geòrgia, additional, Esko, Tõnu, additional, Estivill, Xavier, additional, Farmer, Anne, additional, Favaro, Angela, additional, Fernández‐Aranda, Fernando, additional, Fichter, Manfred M., additional, Fischer, Krista, additional, Föcker, Manuel, additional, Foretova, Lenka, additional, Forstner, Andreas J., additional, Forzan, Monica, additional, Franklin, Christopher S., additional, Gallinger, Steven, additional, Giegling, Ina, additional, Giuranna, Johanna, additional, Gonidakis, Fragiskos, additional, Gorwood, Philip, additional, Gratacos Mayora, Monica, additional, Guillaume, Sébastien, additional, Guo, Yiran, additional, Hakonarson, Hakon, additional, Hatzikotoulas, Konstantinos, additional, Hauser, Joanna, additional, Hebebrand, Johannes, additional, Helder, Sietske G., additional, Herms, Stefan, additional, Herpertz‐Dahlmann, Beate, additional, Herzog, Wolfgang, additional, Huckins, Laura M., additional, Hudson, James I., additional, Imgart, Hartmut, additional, Inoko, Hidetoshi, additional, Janout, Vladimir, additional, Jiménez‐Murcia, Susana, additional, Julià, Antonio, additional, Kalsi, Gursharan, additional, Kaminská, Deborah, additional, Karhunen, Leila, additional, Karwautz, Andreas, additional, Kas, Martien J.H., additional, Kennedy, James L., additional, Keski‐Rahkonen, Anna, additional, Kiezebrink, Kirsty, additional, Kim, Youl‐Ri, additional, Klump, Kelly L., additional, Knudsen, Gun Peggy S., additional, La Via, Maria C., additional, Le Hellard, Stephanie, additional, Levitan, Robert D., additional, Li, Dong, additional, Lilenfeld, Lisa, additional, Lin, Bochao Danae, additional, Lissowska, Jolanta, additional, Luykx, Jurjen, additional, Magistretti, Pierre J., additional, Maj, Mario, additional, Mannik, Katrin, additional, Marsal, Sara, additional, Marshall, Christian R., additional, Mattingsdal, Morten, additional, McDevitt, Sara, additional, McGuffin, Peter, additional, Metspalu, Andres, additional, Meulenbelt, Ingrid, additional, Micali, Nadia, additional, Mitchell, Karen, additional, Monteleone, Alessio Maria, additional, Monteleone, Palmiero, additional, Nacmias, Benedetta, additional, Navratilova, Marie, additional, Ntalla, Ioanna, additional, O'Toole, Julie K., additional, Ophoff, Roel A., additional, Padyukov, Leonid, additional, Palotie, Aarno, additional, Pantel, Jacques, additional, Papezova, Hana, additional, Pinto, Dalila, additional, Rabionet, Raquel, additional, Raevuori, Anu, additional, Ramoz, Nicolas, additional, Reichborn‐Kjennerud, Ted, additional, Ricca, Valdo, additional, Ripatti, Samuli, additional, Ritschel, Franziska, additional, Roberts, Marion, additional, Rotondo, Alessandro, additional, Rujescu, Dan, additional, Rybakowski, Filip, additional, Santonastaso, Paolo, additional, Scherag, André, additional, Scherer, Stephen W., additional, Schmidt, Ulrike, additional, Schork, Nicholas J., additional, Schosser, Alexandra, additional, Seitz, Jochen, additional, Slachtova, Lenka, additional, Slagboom, P. Eline, additional, Slof‐Op't Landt, Margarita C.T., additional, Slopien, Agnieszka, additional, Sorbi, Sandro, additional, Świątkowska, Beata, additional, Szatkiewicz, Jin P., additional, Tachmazidou, Ioanna, additional, Tenconi, Elena, additional, Tortorella, Alfonso, additional, Tozzi, Federica, additional, Treasure, Janet, additional, Tsitsika, Artemis, additional, Tyszkiewicz‐Nwafor, Marta, additional, Tziouvas, Konstantinos, additional, van Elburg, Annemarie A., additional, van Furth, Eric F., additional, Wagner, Gudrun, additional, Walton, Esther, additional, Widen, Elisabeth, additional, Zeggini, Eleftheria, additional, Zerwas, Stephanie, additional, Zipfel, Stephan, additional, Bergen, Andrew W., additional, Boden, Joseph M., additional, Brandt, Harry, additional, Crawford, Steven, additional, Halmi, Katherine A., additional, Horwood, L. John, additional, Johnson, Craig, additional, Kaplan, Allan S., additional, Kaye, Walter H., additional, Mitchell, James, additional, Olsen, Catherine M., additional, Pearson, John F., additional, Pedersen, Nancy L., additional, Strober, Michael, additional, Werge, Thomas, additional, Whiteman, David C., additional, Woodside, D. Blake, additional, Grove, Jakob, additional, Henders, Anjali K., additional, Larsen, Janne T., additional, Parker, Richard, additional, Petersen, Liselotte V., additional, Jordan, Jennifer, additional, Kennedy, Martin A., additional, Birgegård, Andreas, additional, Lichtenstein, Paul, additional, Norring, Claes, additional, Landén, Mikael, additional, Mortensen, Preben Bo, additional, Polimanti, Renato, additional, McClintick, Jeanette N., additional, Adkins, Amy E., additional, Aliev, Fazil, additional, Bacanu, Silviu‐Alin, additional, Batzler, Anthony, additional, Bertelsen, Sarah, additional, Biernacka, Joanna M., additional, Bigdeli, Tim B., additional, Chen, Li‐Shiun, additional, Clarke, Toni‐Kim, additional, Degenhardt, Franziska, additional, Docherty, Anna R., additional, Edwards, Alexis C., additional, Foo, Jerome C., additional, Fox, Louis, additional, Frank, Josef, additional, Hack, Laura M., additional, Hartmann, Annette M., additional, Hartz, Sarah M., additional, Heilmann‐Heimbach, Stefanie, additional, Hodgkinson, Colin, additional, Hoffmann, Per, additional, Hottenga, Jouke‐Jan, additional, Konte, Bettina, additional, Lahti, Jari, additional, Lahti‐Pulkkinen, Marius, additional, Lai, Dongbing, additional, Ligthart, Lannie, additional, Loukola, Anu, additional, Maher, Brion S., additional, Mbarek, Hamdi, additional, McIntosh, Andrew M., additional, McQueen, Matthew B., additional, Meyers, Jacquelyn L., additional, Milaneschi, Yuri, additional, Palviainen, Teemu, additional, Peterson, Roseann E., additional, Ryu, Euijung, additional, Saccone, Nancy L., additional, Salvatore, Jessica E., additional, Sanchez‐Roige, Sandra, additional, Schwandt, Melanie, additional, Sherva, Richard, additional, Streit, Fabian, additional, Strohmaier, Jana, additional, Thomas, Nathaniel, additional, Wang, Jen‐Chyong, additional, Webb, Bradley T., additional, Wedow, Robbee, additional, Wetherill, Leah, additional, Wills, Amanda G., additional, Zhou, Hang, additional, Boardman, Jason D., additional, Chen, Danfeng, additional, Choi, Doo‐Sup, additional, Copeland, William E., additional, Culverhouse, Robert C., additional, Dahmen, Norbert, additional, Degenhardt, Louisa, additional, Domingue, Benjamin W., additional, Frye, Mark A., additional, Gäebel, Wolfgang, additional, Hayward, Caroline, additional, Ising, Marcus, additional, Keyes, Margaret, additional, Kiefer, Falk, additional, Koller, Gabriele, additional, Kramer, John, additional, Kuperman, Samuel, additional, Lucae, Susanne, additional, Lynskey, Michael T., additional, Maier, Wolfgang, additional, Mann, Karl, additional, Männistö, Satu, additional, Müller‐Myhsok, Bertram, additional, Murray, Alison D., additional, Nurnberger, John I., additional, Preuss, Ulrich, additional, Räikkönen, Katri, additional, Reynolds, Maureen D., additional, Ridinger, Monika, additional, Scherbaum, Norbert, additional, Schuckit, Marc A., additional, Soyka, Michael, additional, Treutlein, Jens, additional, Witt, Stephanie H., additional, Wodarz, Norbert, additional, Zill, Peter, additional, Adkins, Daniel E., additional, Boomsma, Dorret I., additional, Bierut, Laura J., additional, Brown, Sandra A., additional, Bucholz, Kathleen K., additional, Costello, E. Jane, additional, de Wit, Harriet, additional, Diazgranados, Nancy, additional, Eriksson, Johan G., additional, Farrer, Lindsay A., additional, Foroud, Tatiana M., additional, Gillespie, Nathan A., additional, Goate, Alison M., additional, Goldman, David, additional, Grucza, Richard A., additional, Hancock, Dana B., additional, Harris, Kathleen Mullan, additional, Hesselbrock, Victor, additional, Hewitt, John K., additional, Hopfer, Christian J., additional, Iacono, William G., additional, Johnson, Eric O., additional, Karpyak, Victor M., additional, Kendler, Kenneth S., additional, Kranzler, Henry R., additional, Krauter, Kenneth, additional, Lind, Penelope A., additional, McGue, Matt, additional, MacKillop, James, additional, Madden, Pamela A.F., additional, Maes, Hermine H., additional, Magnusson, Patrik K.E., additional, Nelson, Elliot C., additional, Nöthen, Markus M., additional, Palmer, Abraham A., additional, Penninx, Brenda W.J.H., additional, Porjesz, Bernice, additional, Rice, John P., additional, Rietschel, Marcella, additional, Riley, Brien P., additional, Rose, Richard J., additional, Shen, Pei‐Hong, additional, Silberg, Judy, additional, Stallings, Michael C., additional, Tarter, Ralph E., additional, Vanyukov, Michael M., additional, Vrieze, Scott, additional, Wall, Tamara L., additional, Whitfield, John B., additional, Zhao, Hongyu, additional, Neale, Benjamin M., additional, Wade, Tracey D., additional, Heath, Andrew C., additional, Montgomery, Grant W., additional, Martin, Nicholas G., additional, Sullivan, Patrick F., additional, Kaprio, Jaakko, additional, Breen, Gerome, additional, Gelernter, Joel, additional, Edenberg, Howard J., additional, Bulik, Cynthia M., additional, and Agrawal, Arpana, additional

Published
2020
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32. Genetic determinants of risk in pulmonary arterial hypertension:international genome-wide association studies and meta-analysis

Author

UK NIHR BioResource Rare Diseases Consortium, UK PAH Cohort Study Consortium, US PAH Biobank Consortium, Rhodes, Christopher J, Batai, Ken, Bleda, Marta, Haimel, Matthias, Southgate, Laura, Germain, Marine, Pauciulo, Michael W, Hadinnapola, Charaka, Aman, Jurjan, Girerd, Barbara, Arora, Amit, Knight, Jo, Hanscombe, Ken B, Karnes, Jason H, Kaakinen, Marika, Gall, Henning, Ulrich, Anna, Harbaum, Lars, Cebola, Inês, Ferrer, Jorge, Lutz, Katie, Swietlik, Emilia M, Ahmad, Ferhaan, Amouyel, Philippe, Archer, Stephen L, Argula, Rahul, Austin, Eric D, Badesch, David, Bakshi, Sahil, Barnett, Christopher, Benza, Raymond, Bhatt, Nitin, Bogaard, Harm J, Burger, Charles D, Chakinala, Murali, Church, Colin, Coghlan, John G, Condliffe, Robin, Corris, Paul A, Danesino, Cesare, Debette, Stéphanie, Elliott, C Gregory, Elwing, Jean, Eyries, Melanie, Fortin, Terry, Franke, Andre, Frantz, Robert P, Frost, Adaani, Garcia, Joe G N, Ghio, Stefano, UK NIHR BioResource Rare Diseases Consortium, UK PAH Cohort Study Consortium, US PAH Biobank Consortium, Rhodes, Christopher J, Batai, Ken, Bleda, Marta, Haimel, Matthias, Southgate, Laura, Germain, Marine, Pauciulo, Michael W, Hadinnapola, Charaka, Aman, Jurjan, Girerd, Barbara, Arora, Amit, Knight, Jo, Hanscombe, Ken B, Karnes, Jason H, Kaakinen, Marika, Gall, Henning, Ulrich, Anna, Harbaum, Lars, Cebola, Inês, Ferrer, Jorge, Lutz, Katie, Swietlik, Emilia M, Ahmad, Ferhaan, Amouyel, Philippe, Archer, Stephen L, Argula, Rahul, Austin, Eric D, Badesch, David, Bakshi, Sahil, Barnett, Christopher, Benza, Raymond, Bhatt, Nitin, Bogaard, Harm J, Burger, Charles D, Chakinala, Murali, Church, Colin, Coghlan, John G, Condliffe, Robin, Corris, Paul A, Danesino, Cesare, Debette, Stéphanie, Elliott, C Gregory, Elwing, Jean, Eyries, Melanie, Fortin, Terry, Franke, Andre, Frantz, Robert P, Frost, Adaani, Garcia, Joe G N, and Ghio, Stefano

Abstract

BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10 -15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10 -20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10 -12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with surv

Published
2019

33. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Author

TN groep Adan, Brain, Circulatory Health, Translational Neuroscience, Hersenen-Bedrijfsvoering, Neurogenetica, Watson, Hunna J, Yilmaz, Zeynep, Thornton, Laura M, Hübel, Christopher, Coleman, Jonathan R I, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Medland, Sarah E, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Purves, Kirstin L, Adan, Roger A H, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Baker, Jessica H, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, 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, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Kas, Martien J H, Lin, Bochao Danae, Ophoff, Roel A, Luykx, Jurjen, Anorexia Nervosa Genetics Initiative, TN groep Adan, Brain, Circulatory Health, Translational Neuroscience, Hersenen-Bedrijfsvoering, Neurogenetica, Watson, Hunna J, Yilmaz, Zeynep, Thornton, Laura M, Hübel, Christopher, Coleman, Jonathan R I, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Medland, Sarah E, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Purves, Kirstin L, Adan, Roger A H, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Baker, Jessica H, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, 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, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Kas, Martien J H, Lin, Bochao Danae, Ophoff, Roel A, Luykx, Jurjen, and Anorexia Nervosa Genetics Initiative

Published
2019

34. Genetic determinants of risk and survival in pulmonary arterial hypertension

Author

Rhodes, Christopher J., Batai, Ken, Bleda, Marta, Haimel, Matthias, Southgate, Laura, Germain, Marine, Pauciulo, Michael W., Hadinnapola, Charaka, Aman, Jurjan, Girerd, Barbara, Arora, Amit, Knight, Jo, Hanscombe, Ken B., Karnes, Jason H., Kaakinen, Marika, Gall, Henning, Ulrich, Anna, Harbaum, Lars, Cebola, Inês, Ferrer, Jorge, Ahmad, Ferhaan, Amouyel, Philippe, Stephen L., Archer, Argula, Rahul, Eric D., Austin, Badesch, David, Bakshi, Sahil, Barnett, Christopher F., Benza, Raymond, Bhatt, Nitin, Bogaard, Harm J., Burger, Charles D., Chakinala, Murali M., Church, Colin, Coghlan, John G., Condliffe, Robin, Corris, Paul A., Danesino, Cesare, Debette, Stéphanie, Elliott, C. Gregory, Elwing, Jean, Eyries, Melanie, Fortin, Terry, Franke, Andre, Frantz, Robert P., Frost, Adaani, Garcia, Joe G.N., Ghio, Stefano, Ghofrani, Hossein-Ardeschir, Simon, J., Gibbs, R., Harley, John B., He, Hua, Hill, Nicholas S., Hirsch, Russel, Houweling, Arjan C., Howard, Luke S., Ivy, Dunbar, Kiely, David G., Klinger, James, Kovacs, Gabor, Lahm, Tim, Laudes, Matthias, Lutz, Katie, Machado, Rajiv D., MacKenzie Ross, Robert V., Marsolo, Keith, Martin, Lisa J., Moledina, Shahin, Montani, David, Nathan, Steven D., Newnham, Michael, Olschewski, Andrea, Olschewski, Horst, Oudiz, Ronald J., Ouwehand, Willem H., Peacock, Andrew J., Pepke-Zaba, Joanna, Rehman, Zia, Robbins, Ivan M., Roden, Dan M., Rosenzweig, Erika B., Saydain, Ghulam, Scelsi, Laura, Schilz, Robert, Seeger, Werner, Shaffer, Christian M., Simms, Robert W., Simon, Marc, Sitbon, Olivier, Suntharalingam, Jay, Swietlik, Emilia, Tang, Haiyang, Tchourbanov, Alexander Y., Thenappan, Thenappan, Torres, Fernando, Toshner, Mark R., Treacy, Carmen M., Noordegraaf, Anton Vonk, Waisfisz, Quinten, Walsworth, Anna K., Walter, Robert E, Wharton, John, White, R. James, Wilt, Jeffrey, Wort, Stephen J., Yung, Delphine, Lawrie, Allan, Humbert, Marc, Soubrier, Florent, Trégouët, David-Alexandre, Prokopenko, Inga, Kittles, Richard, Gräf, Stefan, Nichols, William C., Trembath, Richard C., Desai, Ankit A., Morrell, Nicholas W., and Wilkins, Martin R.

Subjects
0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, 030204 cardiovascular system & hematology, 3. Good health, 030304 developmental biology
Abstract

BackgroundPulmonary arterial hypertension (PAH) is a rare disorder leading to premature death. Rare genetic variants contribute to disease etiology but the contribution of common genetic variation to disease risk and outcome remains poorly characterized.MethodsWe performed two separate genome-wide association studies of PAH using data across 11,744 European-ancestry individuals (including 2,085 patients), one with genotypes from 5,895 whole genome sequences and another with genotyping array data from 5,849 further samples. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. We functionally annotated associated variants and tested associations with duration of survival.FindingsA locus atHLA-DPA1/DPB1within the class II major histocompatibility (MHC) region and a second nearSOX17were significantly associated with PAH. TheSOX17locus contained two independent signals associated with PAH. Functional and epigenomic data indicate that the risk variants nearSOX17alter gene regulation via an enhancer active in endothelial cells. PAH risk variants determined haplotype-specific enhancer activity and CRISPR-inhibition of the enhancer reducedSOX17expression. Analysis of median survival showed that PAH patients with two copies of theHLA-DPA1/DPB1risk variant had a two-fold difference (>16 years versus 8 years), compared to patients homozygous for the alternative allele.InterpretationWe have found that common genetic variation at loci inHLA-DPA1/DPB1and an enhancer nearSOX17are associated with PAH. Impairment of Sox17 function may be more common in PAH than suggested by rare mutations inSOX17. Allelic variation atHLA-DPB1stratifies PAH patients for survival following diagnosis, with implications for future therapeutic trial design.FundingUK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, Inserm, Université Paris-Sud, and French ANR.

Published
2018

35. Shared Genetic Risk between Eating Disorder- and Substance-Use-Related Phenotypes: Evidence from Genome-Wide Association Studies

Author

Munn-Chernoff, Melissa A., primary, Johnson, Emma C., additional, Chou, Yi-Ling, additional, Coleman, Jonathan R.I., additional, Thornton, Laura M., additional, Walters, Raymond K., additional, Yilmaz, Zeynep, additional, Baker, Jessica H., additional, Hübel, Christopher, additional, Gordon, Scott, additional, Medland, Sarah E., additional, Watson, Hunna J., additional, Gaspar, Héléna A., additional, Bryois, Julien, additional, Hinney, Anke, additional, Leppä, Virpi M., additional, Mattheisen, Manuel, additional, Ripke, Stephan, additional, Yao, Shuyang, additional, Giusti-Rodríguez, Paola, additional, Hanscombe, Ken B., additional, Adan, Roger A.H., additional, Alfredsson, Lars, additional, Ando, Tetsuya, additional, Andreassen, Ole A., additional, Berrettini, Wade H., additional, Boehm, Ilka, additional, Boni, Claudette, additional, Perica, Vesna Boraska, additional, Buehren, Katharina, additional, Burghardt, Roland, additional, Cassina, Matteo, additional, Cichon, Sven, additional, Clementi, Maurizio, additional, Cone, Roger D., additional, Courtet, Philippe, additional, Crow, Scott, additional, Crowley, James J., additional, Danner, Unna N., additional, Davis, Oliver S.P., additional, Zwaan, Martina de, additional, Dedoussis, George, additional, Degortes, Daniela, additional, DeSocio, Janiece E., additional, Dick, Danielle M., additional, Dikeos, Dimitris, additional, Dina, Christian, additional, Dmitrzak-Weglarz, Monika, additional, Docampo, Elisa, additional, Duncan, Laramie E., additional, Egberts, Karin, additional, Ehrlich, Stefan, additional, Escaramís, Geòrgia, additional, Esko, Tõnu, additional, Estivill, Xavier, additional, Farmer, Anne, additional, Favaro, Angela, additional, Fernández-Aranda, Fernando, additional, Fichter, Manfred M., additional, Fischer, Krista, additional, Föcker, Manuel, additional, Foretova, Lenka, additional, Forstner, Andreas J., additional, Forzan, Monica, additional, Franklin, Christopher S., additional, Gallinger, Steven, additional, Giegling, Ina, additional, Giuranna, Johanna, additional, Gonidakis, Fragiskos, additional, Gorwood, Philip, additional, Mayora, Monica Gratacos, additional, Guillaume, Sébastien, additional, Guo, Yiran, additional, Hakonarson, Hakon, additional, Hatzikotoulas, Konstantinos, additional, Hauser, Joanna, additional, Hebebrand, Johannes, additional, Helder, Sietske G., additional, Herms, Stefan, additional, Herpertz-Dahlmann, Beate, additional, Herzog, Wolfgang, additional, Huckins, Laura M., additional, Hudson, James I., additional, Imgart, Hartmut, additional, Inoko, Hidetoshi, additional, Janout, Vladimir, additional, Jiménez-Murcia, Susana, additional, Julià, Antonio, additional, Kalsi, Gursharan, additional, Kaminská, Deborah, additional, Karhunen, Leila, additional, Karwautz, Andreas, additional, Kas, Martien J.H., additional, Kennedy, James L., additional, Keski-Rahkonen, Anna, additional, Kiezebrink, Kirsty, additional, Kim, Youl-Ri, additional, Klump, Kelly L., additional, Knudsen, Gun Peggy S., additional, Via, Maria C. La, additional, Hellard, Stephanie Le, additional, Levitan, Robert D., additional, Li, Dong, additional, Lilenfeld, Lisa, additional, Lin, Bochao Danae, additional, Lissowska, Jolanta, additional, Luykx, Jurjen, additional, Magistretti, Pierre J., additional, Maj, Mario, additional, Mannik, Katrin, additional, Marsal, Sara, additional, Marshall, Christian R., additional, Mattingsdal, Morten, additional, McDevitt, Sara, additional, McGuffin, Peter, additional, Metspalu, Andres, additional, Meulenbelt, Ingrid, additional, Micali, Nadia, additional, Mitchell, Karen, additional, Monteleone, Alessio Maria, additional, Monteleone, Palmiero, additional, Nacmias, Benedetta, additional, Navratilova, Marie, additional, Ntalla, Ioanna, additional, O’Toole, Julie K., additional, Ophoff, Roel A., additional, Padyukov, Leonid, additional, Palotie, Aarno, additional, Pantel, Jacques, additional, Papezova, Hana, additional, Pinto, Dalila, additional, Rabionet, Raquel, additional, Raevuori, Anu, additional, Ramoz, Nicolas, additional, Reichborn-Kjennerud, Ted, additional, Ricca, Valdo, additional, Ripatti, Samuli, additional, Ritschel, Franziska, additional, Roberts, Marion, additional, Rotondo, Alessandro, additional, Rujescu, Dan, additional, Rybakowski, Filip, additional, Santonastaso, Paolo, additional, Scherag, André, additional, Scherer, Stephen W., additional, Schmidt, Ulrike, additional, Schork, Nicholas J., additional, Schosser, Alexandra, additional, Seitz, Jochen, additional, Slachtova, Lenka, additional, Slagboom, P. Eline, additional, Slof-Op’t Landt, Margarita C.T., additional, Slopien, Agnieszka, additional, Sorbi, Sandro, additional, Świątkowska, Beata, additional, Szatkiewicz, Jin P., additional, Tachmazidou, Ioanna, additional, Tenconi, Elena, additional, Tortorella, Alfonso, additional, Tozzi, Federica, additional, Treasure, Janet, additional, Tsitsika, Artemis, additional, Tyszkiewicz-Nwafor, Marta, additional, Tziouvas, Konstantinos, additional, Elburg, Annemarie A. van, additional, Furth, Eric F. van, additional, Wagner, Gudrun, additional, Walton, Esther, additional, Widen, Elisabeth, additional, Zeggini, Eleftheria, additional, Zerwas, Stephanie, additional, Zipfel, Stephan, additional, Bergen, Andrew W., additional, Boden, Joseph M., additional, Brandt, Harry, additional, Crawford, Steven, additional, Halmi, Katherine A., additional, Horwood, L. John, additional, Johnson, Craig, additional, Kaplan, Allan S., additional, Kaye, Walter H., additional, Mitchell, James, additional, Olsen, Catherine M., additional, Pearson, John F., additional, Pedersen, Nancy L., additional, Strober, Michael, additional, Werge, Thomas, additional, Whiteman, David C., additional, Woodside, D. Blake, additional, Grove, Jakob, additional, Henders, Anjali K., additional, Larsen, Janne T., additional, Parker, Richard, additional, Petersen, Liselotte V., additional, Jordan, Jennifer, additional, Kennedy, Martin A., additional, Birgegård, Andreas, additional, Lichtenstein, Paul, additional, Norring, Claes, additional, Landén, Mikael, additional, Mortensen, Preben Bo, additional, Polimanti, Renato, additional, McClintick, Jeanette N., additional, Adkins, Amy E., additional, Aliev, Fazil, additional, Bacanu, Silviu-Alin, additional, Batzler, Anthony, additional, Bertelsen, Sarah, additional, Biernacka, Joanna M., additional, Bigdeli, Tim B., additional, Chen, Li-Shiun, additional, Clarke, Toni-Kim, additional, Degenhardt, Franziska, additional, Docherty, Anna R., additional, Edwards, Alexis C., additional, Foo, Jerome C., additional, Fox, Louis, additional, Frank, Josef, additional, Hack, Laura M., additional, Hartmann, Annette M., additional, Hartz, Sarah M., additional, Heilmann-Heimbach, Stefanie, additional, Hodgkinson, Colin, additional, Hoffmann, Per, additional, Hottenga, Jouke-Jan, additional, Konte, Bettina, additional, Lahti, Jari, additional, Lahti-Pulkkinen, Marius, additional, Lai, Dongbing, additional, Ligthart, Lannie, additional, Loukola, Anu, additional, Maher, Brion S., additional, Mbarek, Hamdi, additional, McIntosh, Andrew M., additional, McQueen, Matthew B., additional, Meyers, Jacquelyn L., additional, Milaneschi, Yuri, additional, Palviainen, Teemu, additional, Peterson, Roseann E., additional, Ryu, Euijung, additional, Saccone, Nancy L., additional, Salvatore, Jessica E., additional, Sanchez-Roige, Sandra, additional, Schwandt, Melanie, additional, Sherva, Richard, additional, Streit, Fabian, additional, Strohmaier, Jana, additional, Thomas, Nathaniel, additional, Wang, Jen-Chyong, additional, Webb, Bradley T., additional, Wedow, Robbee, additional, Wetherill, Leah, additional, Wills, Amanda G., additional, Zhou, Hang, additional, Boardman, Jason D., additional, Chen, Danfeng, additional, Choi, Doo-Sup, additional, Copeland, William E., additional, Culverhouse, Robert C., additional, Dahmen, Norbert, additional, Degenhardt, Louisa, additional, Domingue, Benjamin W., additional, Frye, Mark A., additional, Gäbel, Wolfgang, additional, Hayward, Caroline, additional, Ising, Marcus, additional, Keyes, Margaret, additional, Kiefer, Falk, additional, Koller, Gabrielle, additional, Kramer, John, additional, Kuperman, Samuel, additional, Lucae, Susanne, additional, Lynskey, Michael T., additional, Maier, Wolfgang, additional, Mann, Karl, additional, Männistö, Satu, additional, Müller-Myhsok, Bertram, additional, Murray, Alison D., additional, Nurnberger, John I., additional, Preuss, Ulrich, additional, Räikkönen, Katri, additional, Reynolds, Maureen D., additional, Ridinger, Monika, additional, Scherbaum, Norbert, additional, Schuckit, Marc A., additional, Soyka, Michael, additional, Treutlein, Jens, additional, Witt, Stephanie H., additional, Wodarz, Norbert, additional, Zill, Peter, additional, Adkins, Daniel E., additional, Boomsma, Dorret I., additional, Bierut, Laura J., additional, Brown, Sandra A., additional, Bucholz, Kathleen K., additional, Costello, E. Jane, additional, Wit, Harriet de, additional, Diazgranados, Nancy, additional, Eriksson, Johan G., additional, Farrer, Lindsay A., additional, Foroud, Tatiana M., additional, Gillespie, Nathan A., additional, Goate, Alison M., additional, Goldman, David, additional, Grucza, Richard A., additional, Hancock, Dana B., additional, Harris, Kathleen Mullan, additional, Hesselbrock, Victor, additional, Hewitt, John K., additional, Hopfer, Christian J., additional, Iacono, William G., additional, Johnson, Eric O., additional, Karpyak, Victor M., additional, Kendler, Kenneth S., additional, Kranzler, Henry R., additional, Krauter, Kenneth, additional, Lind, Penelope A., additional, McGue, Matt, additional, MacKillop, James, additional, Madden, Pamela A.F., additional, Maes, Hermine H., additional, Magnusson, Patrik K.E., additional, Nelson, Elliot C., additional, Nöthen, Markus M., additional, Palmer, Abraham A., additional, Penninx, Brenda W.J.H., additional, Porjesz, Bernice, additional, Rice, John P., additional, Rietschel, Marcella, additional, Riley, Brien P., additional, Rose, Richard J., additional, Shen, Pei-Hong, additional, Silberg, Judy, additional, Stallings, Michael C., additional, Tarter, Ralph E., additional, Vanyukov, Michael M., additional, Vrieze, Scott, additional, Wall, Tamara L., additional, Whitfield, John B., additional, Zhao, Hongyu, additional, Neale, Benjamin M., additional, Wade, Tracey D., additional, Heath, Andrew C., additional, Montgomery, Grant W., additional, Martin, Nicholas G., additional, Sullivan, Patrick F., additional, Kaprio, Jaakko, additional, Breen, Gerome, additional, Gelernter, Joel, additional, Edenberg, Howard J., additional, Bulik, Cynthia M., additional, and Agrawal, Arpana, additional

Published
2019
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38. Genetic Variation at 16q24.2 is associated with small vessel stroke:16q24.2 and small vessel stroke

Author

Traylor, Matthew, Malik, Rainer, Nalls, Mike A., Cotlarciuc, Ioana, Radmanesh, Farid, Thorleifsson, Gudmar, Hanscombe, Ken B., Langefeld, Carl, Saleheen, Danish, Rost, Natalia S., Yet, Idil, Spector, Tim D., Bell, Jordana T., Hannon, Eilis, Mill, Jonathan, Chauhan, Ganesh, Debette, Stephanie, Bis, Joshua C., Longstreth, Wt, Ikram, M. Arfan, Launer, Lenore J., Seshadri, Sudha, Jimenez-conde, Jordi, Cole, John W., Schmidt, Reinhold, Słowik, Agnieszka, Lemmens, Robin, Lindgren, Arne, Melander, Olle, Grewal, Raji P., Sacco, Ralph L., Rundek, Tatjana, Rexrode, Kathryn, Arnett, Donna K., Johnson, Julie A., Benavente, Oscar R., Wasssertheil-smoller, Sylvia, Lee, Jin-moo, Pulit, Sara L., Wong, Quenna, Rich, Stephen S., De Bakker, Paul I.w., Mcardle, Patrick F., Woo, Daniel, Anderson, Christopher D., Xu, Huichun, Heitsch, Laura, Fornage, Myriam, Jern, Christina, Stefansson, Kari, Thorsteinsdottir, Unnur, Gretarsdottir, Solveig, Lewis, Cathryn M., Sharma, Pankaj, Sudlow, Catherine, Rothwell, Peter M., Boncoraglio, Giorgio B., Thijs, Vincent, Levi, Chris, Meschia, James F., Rosand, Jonathan, Kittner, Steven J., Mitchell, Braxton D., Dichgans, Martin, Worrall, Bradford B., and Markus, Hugh S.

Abstract

Objective: Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises a quarter of all ischaemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown younger onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger onset SVS population, to identify novel associations with stroke.Methods: We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on mRNA expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain.Results: We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (OR(95% CI)=1.16(1.10-1.22); p=3.2x10−9). The lead SNP (rs12445022) was also associated with cerebral white matter hyperintensities (OR(95% CI)=1.10(1.05-1.16); p=5.3x10−5; N=3,670), but not intracerebral haemorrhage (OR(95% CI)=0.97(0.84-1.12); p=0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p=9.4x10−7), and DNA methylation at probe cg16596957 in whole blood (p=5.3x10−6).Interpretation: 16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements. This article is protected by copyright. All rights reserved.

Published
2016

39. Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent.

Author

Hübel, Christopher, Gaspar, Héléna A., Coleman, Jonathan R. I., Hanscombe, Ken B., Purves, Kirstin, Prokopenko, Inga, Graff, Mariaelisa, Ngwa, Julius S., Workalemahu, Tsegaselassie, O'Reilly, Paul F., Bulik, Cynthia M., and Breen, Gerome

Subjects
MENTAL illness & physiology, GENETIC correlations, HUMAN body composition, HUMAN genetic variation, MENDEL'S law
Abstract

Body composition is often altered in psychiatric disorders. Using genome-wide common genetic variation data, we calculate sex-specific genetic correlations amongst body fat %, fat mass, fat-free mass, physical activity, glycemic traits and 17 psychiatric traits (up to N = 217,568). Two patterns emerge: (1) anorexia nervosa, schizophrenia, obsessive-compulsive disorder, and education years are negatively genetically correlated with body fat % and fat-free mass, whereas (2) attention-deficit/hyperactivity disorder (ADHD), alcohol dependence, insomnia, and heavy smoking are positively correlated. Anorexia nervosa shows a stronger genetic correlation with body fat % in females, whereas education years is more strongly correlated with fat mass in males. Education years and ADHD show genetic overlap with childhood obesity. Mendelian randomization identifies schizophrenia, anorexia nervosa, and higher education as causal for decreased fat mass, with higher body fat % possibly being a causal risk factor for ADHD and heavy smoking. These results suggest new possibilities for targeted preventive strategies. Psychiatric disorders are often accompanied by alterations in BMI and body composition due to changes in eating behaviour and physical activity. Here, Hübel et al. study the genetic overlap between these traits and find that genetic correlations between psychiatric disorders and body composition are sex-specific and evident only in adulthood. [ABSTRACT FROM AUTHOR]

Published
2019
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40. Genetic fine mapping of systemic lupus erythematosus MHC associations in Europeans and African Americans

Author

Hanscombe, Ken B, primary, Morris, David L, additional, Noble, Janelle A, additional, Dilthey, Alexander T, additional, Tombleson, Philip, additional, Kaufman, Kenneth M, additional, Comeau, Mary, additional, Langefeld, Carl D, additional, Alarcon-Riquelme, Marta E, additional, Gaffney, Patrick M, additional, Jacob, Chaim O, additional, Sivils, Kathy L, additional, Tsao, Betty P, additional, Alarcon, Graciela S, additional, Brown, Elizabeth E, additional, Croker, Jennifer, additional, Edberg, Jeff, additional, Gilkeson, Gary, additional, James, Judith A, additional, Kamen, Diane L, additional, Kelly, Jennifer A, additional, McCune, Joseph, additional, Merrill, Joan T, additional, Petri, Michelle, additional, Ramsey-Goldman, Rosalind, additional, Reveille, John D, additional, Salmon, Jane E, additional, Scofield, Hal, additional, Utset, Tammy, additional, Wallace, Daniel J, additional, Weisman, Michael H, additional, Kimberly, Robert P, additional, Harley, John B, additional, Lewis, Cathryn M, additional, Criswell, Lindsey A, additional, and Vyse, Timothy J, additional

Published
2018
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41. Predictors of intestinal inflammation in asymptomatic first-degree relatives of patients with Crohn’s disease

Author

Taylor, Kirstin M., primary, Hanscombe, Ken B., additional, Iniesta, Raquel, additional, Traylor, Matthew, additional, Taylor, Nicola S., additional, Powell, Nicholas, additional, Irving, Peter M., additional, Anderson, Simon H., additional, Prescott, Natalie J., additional, Mathew, Christopher G., additional, Lewis, Cathryn M., additional, and Sanderson, Jeremy D., additional

Published
2017
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43. Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke

Author

Hanscombe, Ken B, Traylor, Matthew, Hysi, Pirro G, Bevan, Stephen, Dichgans, Martin, Rothwell, Peter M, Worrall, Bradford B, Seshadri, Sudha, Sudlow, Cathie, Williams, Frances M K, Markus, Hugh S, and Lewis, Cathryn M

Subjects
Male, Factor XIII, Polymorphism, Single Nucleotide, Brain Ischemia, Cohort Studies, Stroke, Meta-Analysis as Topic, Risk Factors, Case-Control Studies, Diseases in Twins, Humans, Twin Studies as Topic, Female, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract

BACKGROUND AND PURPOSE: Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes.METHODS: Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke.RESULTS: One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03).CONCLUSIONS: Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype.

Published
2015

45. The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Author

Davis, Oliver S. P., Band, Gavin, Pirinen, Matti, Haworth, Claire M. A., Meaburn, Emma L., Kovas, Yulia, Harlaar, Nicole, Docherty, Sophia J., Hanscombe, Ken B., Trzaskowski, Maciej, Curtis, Charles J. C., Strange, Amy, Freeman, Colin, Bellenguez, Céline, Su, Zhan, Pearson, Richard, Vukcevic, Damjan, Langford, Cordelia, Deloukas, Panos, Hunt, Sarah, Gray, Emma, Dronov, Serge, Potter, Simon C., Tashakkori-Ghanbaria, Avazeh, Edkins, Sarah, Bumpstead, Suzannah J., Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Corvin, Aiden, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S., Mathew, Christopher G., Palmer, Colin N. A., Rautanen, Anna, Sawcer, Stephen J., Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas W., Barroso, Ines, Peltonen, Leena, Dale, Philip S., Petrill, Stephen A., Schalkwyk, Leonard S., Craig, Ian W., Lewis, Cathryn M., Price, Thomas S., Donnelly, Peter, Plomin, Robert, and Spencer, Chris C. A.

Subjects
Male, LB1501, RJ, Twins, BF, A300, Polymorphism, Single Nucleotide, Article, United Kingdom, Dyslexia, psyc, Genetics, Population, Quantitative Trait, Heritable, Reading, HQ, Humans, Learning, Female, LB, Child, Mathematics, Genome-Wide Association Study
Abstract

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve., Understanding the genetic basis of cognitive traits could aid the development of numeracy and literacy skills in children. Here the authors show that reading and mathematics have a large overlapping genetic component and suggest that a child's learning environment has a key role in creating differences between them.

Published
2014

47. Trajectories of Callous-Unemotional Traits in Childhood Predict Different Forms of Peer Victimization in Adolescence.

Author

Fontaine, Nathalie M. G., Hanscombe, Ken B., Berg, Mark T., McCrory, Eamon J., and Viding, Essi

Subjects
*CHILD psychology, *ADOLESCENCE, *SOCIAL skills, *SOCIAL interaction, *DELINQUENT behavior
Abstract

Callous-unemotional (CU) traits (e.g., lack of empathy and guilt) differentiate a group of children at particularly high risk for engaging in aggressive behavior, notably bullying. However, little is known about whether youths with CU traits are at risk for being victimized by their peers. We examined the associations between trajectories of CU traits in childhood (between 7 and 12 years old) and peer victimization in adolescence (14 years old). The participants were drawn from the Twins Early Development Study, a longitudinal population-based study of twins born in England and inWales. The trajectories of CU traits (i.e., stable high, increasing, decreasing and stable low) were identified through general growth mixture modeling. Four forms of peer victimization were considered: physical victimization, verbal victimization, social manipulation, and attacks on property. We found that youths with stable high levels, increasing levels, and decreasing levels of CU traits in childhood had higher levels of physical victimization in adolescence, not explained by other predictors at age 7 (e.g., conduct problems). Youths with increasing levels of CU traits, compared with the ones with stable low levels, also had higher levels of verbal victimization, social manipulation, and attacks on property. Our findings highlight the importance of distinct trajectories of CU traits in accounting for the experience of different forms of peer victimization. Youths with CU traits may benefit from bullying prevention programs, as they are likely to be the targets of peer victimization. [ABSTRACT FROM AUTHOR]

Published
2018
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