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

Author

Ip, Hill, van der Laan, Camiel, Krapohl, Eva, Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja, St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol, Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke, Adkins, Daniel, Border, Richard, Peterson, Roseann, Prinz, Joseph, Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer, Day, Felix, Hottenga, Jouke-Jan, Allegrini, Andrea, Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José, Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James, Vinkhuyzen, Anna, Shabalin, Andrey, Corley, Robin, Evans, Luke, Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth, Ehli, Erik, Hagenbeek, Fiona, De Zeeuw, Eveline, Van Beijsterveldt, Toos, Larsson, Henrik, Snieder, Harold, Verhulst, Frank, Amin, Najaf, Whipp, Alyce, Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard, Uitterlinden, André, Heath, Andrew, Madden, Pamela, Haavik, Jan, Harris, Jennifer, Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun, Njolstad, Pal, Lu, Qing, Rodriguez, Alina, Henders, Anjali, Mamun, Abdullah, Najman, Jackob, Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara, Silberg, Judy, Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, and Raitakari, Olli

Subjects
Adolescent, Aggression, Child, Child, Preschool, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Infant, Mental Disorders, Retrospective Studies
Abstract

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

Published
2021

3. Genetics and the geography of health, behaviour and attainment

Author

Belsky, Daniel W, Caspi, Avshalom, Arseneault, Louise, Corcoran, David L, Domingue, Benjamin W, Harris, Kathleen Mullan, Houts, Renate M, Mill, Jonathan S, Moffitt, Terrie E, Prinz, Joseph, Sugden, Karen, Wertz, Jasmin, Williams, Benjamin, and Odgers, Candice L

Subjects
Public Health, Health Sciences, Pediatric, Mental Health, Aetiology, 2.3 Psychological, social and economic factors, Mental health, Generic health relevance, Good Health and Well Being, Adolescent, Adult, Child, Child, Preschool, Educational Status, England, Female, Genetic Predisposition to Disease, Health Surveys, Humans, Infant, Longitudinal Studies, Male, Obesity, Pregnancy, Pregnancy in Adolescence, Residence Characteristics, Risk Assessment, Schizophrenia, Socioeconomic Factors, United States, Wales, Young Adult, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Young people's life chances can be predicted by characteristics of their neighbourhood1. Children growing up in disadvantaged neighbourhoods exhibit worse physical and mental health and suffer poorer educational and economic outcomes than children growing up in advantaged neighbourhoods. Increasing recognition that aspects of social inequalities tend, in fact, to be geographical inequalities2-5 is stimulating research and focusing policy interest on the role of place in shaping health, behaviour and social outcomes. Where neighbourhood effects are causal, neighbourhood-level interventions can be effective. Where neighbourhood effects reflect selection of families with different characteristics into different neighbourhoods, interventions should instead target families or individuals directly. To test how selection may affect different neighbourhood-linked problems, we linked neighbourhood data with genetic, health and social outcome data for >7,000 European-descent UK and US young people in the E-Risk and Add Health studies. We tested selection/concentration of genetic risks for obesity, schizophrenia, teen pregnancy and poor educational outcomes in high-risk neighbourhoods, including genetic analysis of neighbourhood mobility. Findings argue against genetic selection/concentration as an explanation for neighbourhood gradients in obesity and mental health problems. By contrast, modest genetic selection/concentration was evident for teen pregnancy and poor educational outcomes, suggesting that neighbourhood effects for these outcomes should be interpreted with care.

Published
2019

4. Using DNA from Mothers and Children to Study Parental Investment in Children's Educational Attainment

Author

Wertz, Jasmin, Moffitt, Terrie E., Agnew-Blais, Jessica, Arseneault, Louise, Belsky, Daniel W., Corcoran, David L., Houts, Renate, Matthews, Timothy, Prinz, Joseph A., Richmond-Rakerd, Leah S., Sugden, Karen, Williams, Benjamin, and Caspi, Avshalom

Abstract

This study tested implications of new genetic discoveries for understanding the association between parental investment and children's educational attainment. A novel design matched genetic data from 860 British mothers and their children with home-visit measures of parenting: the E-Risk Study. Three findings emerged. First, both mothers' and children's education-associated genetics, summarized in a genome-wide polygenic score, were associated with parenting--a gene-environment correlation. Second, accounting for genetic influences slightly reduced associations between parenting and children's attainment--indicating some genetic confounding. Third, mothers' genetics were associated with children's attainment over and above children's own genetics, via cognitively stimulating parenting--an environmentally mediated effect. Findings imply that, when interpreting parents' effects on children, environmentalists must consider genetic transmission, but geneticists must also consider environmental transmission.

Published
2020
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5. Genetic changes from type I interferons and JAK inhibitors: clues to drivers of juvenile dermatomyositis.

Author

Covert, Lauren T, Prinz, Joseph A, Swain-Lenz, Devjanee, Dvergsten, Jeffrey, and Truskey, George A

Subjects
*DERMATOMYOSITIS, *SKELETAL muscle, *PHENOMENOLOGICAL biology, *TREATMENT effectiveness, *CELLULAR signal transduction, *BIOCHEMISTRY, *INTERFERONS, *JANUS kinases, *GENE expression, *GENE expression profiling, *NEUROTRANSMITTER uptake inhibitors, *CYTOKINES, *MUSCLES, *SEQUENCE analysis
Abstract

Objective To better understand the pathogenesis of juvenile dermatomyositis (JDM), we examined the effect of the cytokines type I interferons (IFN I) and JAK inhibitor drugs (JAKi) on gene expression in bioengineered pediatric skeletal muscle. Methods Myoblasts from three healthy pediatric donors were used to create three-dimensional skeletal muscle units termed myobundles. Myobundles were treated with IFN I, either IFNα or IFNβ. A subset of IFNβ-exposed myobundles was treated with JAKi tofacitinib or baricitinib. RNA sequencing analysis was performed on all myobundles. Results Seventy-six myobundles were analysed. Principal component analysis showed donor-specific clusters of gene expression across IFNα and IFNβ-exposed myobundles in a dose-dependent manner. Both cytokines upregulated interferon response and proinflammatory genes; however, IFNβ led to more significant upregulation. Key downregulated pathways involved oxidative phosphorylation, fatty acid metabolism and myogenesis genes. Addition of tofacitinib or baricitinib moderated the gene expression induced by IFNβ, with partial reversal of upregulated inflammatory and downregulated myogenesis pathways. Baricitinib altered genetic profiles more than tofacitinib. Conclusion IFNβ leads to more pro-inflammatory gene upregulation than IFNα, correlating to greater decrease in contractile protein gene expression and reduced contractile force. JAK inhibitors, baricitinib more so than tofacitinib, partially reverse IFN I-induced genetic changes. Increased IFN I exposure in healthy bioengineered skeletal muscle leads to IFN-inducible gene expression, inflammatory pathway enrichment, and myogenesis gene downregulation, consistent with what is observed in JDM. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction

Author

Demange, Perline A., Malanchini, Margherita, Mallard, Travis T., Biroli, Pietro, Cox, Simon R., Grotzinger, Andrew D., Tucker-Drob, Elliot M., Abdellaoui, Abdel, Arseneault, Louise, van Bergen, Elsje, Boomsma, Dorret I., Caspi, Avshalom, Corcoran, David L., Domingue, Benjamin W., Harris, Kathleen Mullan, Ip, Hill F., Mitchell, Colter, Moffitt, Terrie E., Poulton, Richie, Prinz, Joseph A., Sugden, Karen, Wertz, Jasmin, Williams, Benjamin S., de Zeeuw, Eveline L., Belsky, Daniel W., Harden, K. Paige, and Nivard, Michel G.

Published
2021
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10. Exome sequencing of hepatocellular carcinoma in lemurs identifies potential cancer drivers: A pilot study

Author

Gunady, Ella F, Ware, Kathryn E, Plumlee, Sarah Hoskinson, Devos, Nicolas, Corcoran, David, Prinz, Joseph, Misetic, Hrvoje, Ciccarelli, Francesca D, Harrison, Tara M, Thorne, Jeffrey L, Schopler, Robert, Everitt, Jeffrey I, Eward, William C, and Somarelli, Jason A

Subjects
Genome Integrity & Repair, Gene Expression, Genetics & Genomics, Computational & Systems Biology
Abstract

Background and objectives: Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers in this group is unknown. Characterizing the genetic changes associated with hepatocellular carcinoma in prosimians may point to possible causes, treatments and methods of prevention, aiding conservation efforts that are particularly crucial to the survival of endangered lemurs. Although genomic studies of cancer in non-human primates have been hampered by a lack of tools, recent studies have demonstrated the efficacy of using human exome capture reagents across primates. Methodology: In this proof-of-principle study, we applied human exome capture reagents to tumor-normal pairs from five lemurs with hepatocellular carcinoma to characterize the mutational landscape of this disease in lemurs. Results: Several genes implicated in human hepatocellular carcinoma, including ARID1A, TP53 and CTNNB1, were mutated in multiple lemurs, and analysis of cancer driver genes mutated in these samples identified enrichment of genes involved with TP53 degradation and regulation. In addition to these similarities with human hepatocellular carcinoma, we also noted unique features, including six genes that contain mutations in all five lemurs. Interestingly, these genes are infrequently mutated in human hepatocellular carcinoma, suggesting potential differences in the etiology and/or progression of this cancer in lemurs and humans. Conclusions and implications: Collectively, this pilot study suggests that human exome capture reagents are a promising tool for genomic studies of cancer in lemurs and other non-human primates. Lay Summary: Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers is unknown. In this proof-of-principle study, we applied human DNA sequencing tools to tumor-normal pairs from five lemurs with hepatocellular carcinoma and compared the lemur mutation profiles to those of human hepatocellular carcinomas.

Published
2022
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12. Continuity of Genetic Risk for Aggressive Behavior Across the Life-Course

Author

van der Laan, Camiel M., Morosoli-García, José J., van de Weijer, Steve G.A., Colodro-Conde, Lucía, Ip, Hill F., Krapohl, Eva M.L., Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja M., Pourcain, Beate St, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol A., Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke R., Adkins, Daniel E., Border, Richard, Peterson, Roseann E., Prinz, Joseph A., Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer S., Day, Felix R., Allegrini, Andrea G., Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Artigas, María Soler, Rovira, Paula, Bosch, Rosa, Español, Gemma, Neumann, Alexander, Middeldorp, Christel, Verhulst, Frank C., Amin, Najaf, Uitterlinden, André G., Perry, John R.B., Heinrich, Joachim, Tiemeier, Henning, Bartels, Meike, Hottenga, Jouke Jan, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Internal Medicine, Ophthalmology, Epidemiology, Public Health, Adult Psychiatry, Epidemiology and Data Science, APH - Aging & Later Life, APH - Methodology, AR&D - Amsterdam Reproduction & Development, Graduate School, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, Public and occupational health, APH - Health Behaviors & Chronic Diseases, ACS - Pulmonary hypertension & thrombosis, Biological Psychology, Criminology, APH - Mental Health, APH - Personalized Medicine, Life Course Epidemiology (LCE), Macromolecular Chemistry & New Polymeric Materials, and Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)

Subjects
Adult, medicine.medical_specialty, Multifactorial Inheritance, Adolescent, 0608 Zoology, Development, Young Adult, Life-course, Risk Factors, Polygenic score, Genetics, medicine, ACTION Consortium, Humans, Genetic risk, Child, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Aged, Netherlands, Original Research, Genetics & Heredity, Aggression, Public health, Australia, Aggressive behavior, Middle Aged, Rolling weights, Early life, Health psychology, 1701 Psychology, Life course approach, medicine.symptom, Psychology, 1109 Neurosciences, Demography
Abstract

We test whether genetic influences that explain individual differences in aggression in early life also explain individual differences across the life-course. In two cohorts from The Netherlands (N = 13,471) and Australia (N = 5628), polygenic scores (PGSs) were computed based on a genome-wide meta-analysis of childhood/adolescence aggression. In a novel analytic approach, we ran a mixed effects model for each age (Netherlands: 12–70 years, Australia: 16–73 years), with observations at the focus age weighted as 1, and decaying weights for ages further away. We call this approach a ‘rolling weights’ model. In The Netherlands, the estimated effect of the PGS was relatively similar from age 12 to age 41, and decreased from age 41–70. In Australia, there was a peak in the effect of the PGS around age 40 years. These results are a first indication from a molecular genetics perspective that genetic influences on aggressive behavior that are expressed in childhood continue to play a role later in life. Supplementary Information The online version contains supplementary material available at 10.1007/s10519-021-10076-6.

Published
2021
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13. Genetic association study of childhood aggression across raters, instruments, and age

Author

Ip, Hill F., van der Laan, Camiel M., Krapohl, Eva M.L., Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja M., St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol A., Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke R., Adkins, Daniel E., Border, Richard, Peterson, Roseann E., Prinz, Joseph A., Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer S., Day, Felix R., Hottenga, Jouke Jan, Allegrini, Andrea G., Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep Antoni, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José J., Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James G., Vinkhuyzen, Anna, Shabalin, Andrey A., Corley, Robin, Evans, Luke M., Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth E., Ehli, Erik A., Hagenbeek, Fiona A., De Zeeuw, Eveline, Van Beijsterveldt, Toos C.E.M., Larsson, Henrik, Snieder, Harold, Verhulst, Frank C., Amin, Najaf, Whipp, Alyce M., Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard J., Uitterlinden, André G., Heath, Andrew C., Madden, Pamela, Haavik, Jan, Harris, Jennifer R., Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun Peggy S., Njolstad, Pal Rasmus, Lu, Qing, Rodriguez, Alina, Henders, Anjali K., Mamun, Abdullah, Najman, Jackob M., Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara L., Silberg, Judy L., Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, Raitakari, Olli T., Perry, John R.B., Llop, Sabrina, Lopez-Espinosa, Maria Jose, Bønnelykke, Klaus, Bisgaard, Hans, Sunyer, Jordi, Lehtimäki, Terho, Arseneault, Louise, Standl, Marie, Heinrich, Joachim, Boden, Joseph, Pearson, John, Horwood, L. John, Kennedy, Martin, Poulton, Richie, Eaves, Lindon J., Maes, Hermine H., Hewitt, John, Copeland, William E., Costello, Elizabeth J., Williams, Gail M., Wray, Naomi, Järvelin, Marjo Riitta, McGue, Matt, Iacono, William, Caspi, Avshalom, Moffitt, Terrie E., Whitehouse, Andrew, Pennell, Craig E., Klump, Kelly L., Burt, S. Alexandra, Dick, Danielle M., Reichborn-Kjennerud, Ted, Martin, Nicholas G., Medland, Sarah E., Vrijkotte, Tanja, Kaprio, Jaakko, Tiemeier, Henning, Davey Smith, George, Hartman, Catharina A., Oldehinkel, Albertine J., Casas, Miquel, Ribasés, Marta, Lichtenstein, Paul, Lundström, Sebastian, Plomin, Robert, Bartels, Meike, Nivard, Michel G., Boomsma, Dorret I., Ip, Hill F., van der Laan, Camiel M., Krapohl, Eva M.L., Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja M., St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol A., Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke R., Adkins, Daniel E., Border, Richard, Peterson, Roseann E., Prinz, Joseph A., Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer S., Day, Felix R., Hottenga, Jouke Jan, Allegrini, Andrea G., Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep Antoni, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José J., Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James G., Vinkhuyzen, Anna, Shabalin, Andrey A., Corley, Robin, Evans, Luke M., Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth E., Ehli, Erik A., Hagenbeek, Fiona A., De Zeeuw, Eveline, Van Beijsterveldt, Toos C.E.M., Larsson, Henrik, Snieder, Harold, Verhulst, Frank C., Amin, Najaf, Whipp, Alyce M., Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard J., Uitterlinden, André G., Heath, Andrew C., Madden, Pamela, Haavik, Jan, Harris, Jennifer R., Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun Peggy S., Njolstad, Pal Rasmus, Lu, Qing, Rodriguez, Alina, Henders, Anjali K., Mamun, Abdullah, Najman, Jackob M., Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara L., Silberg, Judy L., Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, Raitakari, Olli T., Perry, John R.B., Llop, Sabrina, Lopez-Espinosa, Maria Jose, Bønnelykke, Klaus, Bisgaard, Hans, Sunyer, Jordi, Lehtimäki, Terho, Arseneault, Louise, Standl, Marie, Heinrich, Joachim, Boden, Joseph, Pearson, John, Horwood, L. John, Kennedy, Martin, Poulton, Richie, Eaves, Lindon J., Maes, Hermine H., Hewitt, John, Copeland, William E., Costello, Elizabeth J., Williams, Gail M., Wray, Naomi, Järvelin, Marjo Riitta, McGue, Matt, Iacono, William, Caspi, Avshalom, Moffitt, Terrie E., Whitehouse, Andrew, Pennell, Craig E., Klump, Kelly L., Burt, S. Alexandra, Dick, Danielle M., Reichborn-Kjennerud, Ted, Martin, Nicholas G., Medland, Sarah E., Vrijkotte, Tanja, Kaprio, Jaakko, Tiemeier, Henning, Davey Smith, George, Hartman, Catharina A., Oldehinkel, Albertine J., Casas, Miquel, Ribasés, Marta, Lichtenstein, Paul, Lundström, Sebastian, Plomin, Robert, Bartels, Meike, Nivard, Michel G., and Boomsma, Dorret I.

Abstract

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range ∣ rg∣ : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range ∣ rg∣ : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- an

Published
2021

14. Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm

Author

Belsky, Daniel W, primary, Caspi, Avshalom, additional, Arseneault, Louise, additional, Baccarelli, Andrea, additional, Corcoran, David L, additional, Gao, Xu, additional, Hannon, Eiliss, additional, Harrington, Hona Lee, additional, Rasmussen, Line JH, additional, Houts, Renate, additional, Huffman, Kim, additional, Kraus, William E, additional, Kwon, Dayoon, additional, Mill, Jonathan, additional, Pieper, Carl F, additional, Prinz, Joseph A, additional, Poulton, Richie, additional, Schwartz, Joel, additional, Sugden, Karen, additional, Vokonas, Pantel, additional, Williams, Benjamin S, additional, and Moffitt, Terrie E, additional

Published
2020
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15. Author response: Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm

Author

Belsky, Daniel W, primary, Caspi, Avshalom, additional, Arseneault, Louise, additional, Baccarelli, Andrea, additional, Corcoran, David L, additional, Gao, Xu, additional, Hannon, Eiliss, additional, Harrington, Hona Lee, additional, Rasmussen, Line JH, additional, Houts, Renate, additional, Huffman, Kim, additional, Kraus, William E, additional, Kwon, Dayoon, additional, Mill, Jonathan, additional, Pieper, Carl F, additional, Prinz, Joseph A, additional, Poulton, Richie, additional, Schwartz, Joel, additional, Sugden, Karen, additional, Vokonas, Pantel, additional, Williams, Benjamin S, additional, and Moffitt, Terrie E, additional

Published
2020
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16. From the Clinic to the Bench and Back Again in One Dog Year: How a Cross-Species Pipeline to Identify New Treatments for Sarcoma Illuminates the Path Forward in Precision Medicine

Author

Rao, Sneha R., primary, Somarelli, Jason A., additional, Altunel, Erdem, additional, Selmic, Laura E., additional, Byrum, Mark, additional, Sheth, Maya U., additional, Cheng, Serene, additional, Ware, Kathryn E., additional, Kim, So Young, additional, Prinz, Joseph A., additional, Devos, Nicolas, additional, Corcoran, David L., additional, Moseley, Arthur, additional, Soderblom, Erik, additional, Hsu, S. David, additional, and Eward, William C., additional

Published
2020
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17. Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

Author

Demange, Perline A., primary, Malanchini, Margherita, additional, Mallard, Travis T., additional, Biroli, Pietro, additional, Cox, Simon R., additional, Grotzinger, Andrew D., additional, Tucker-Drob, Elliot M., additional, Abdellaoui, Abdel, additional, Arseneault, Louise, additional, Caspi, Avshalom, additional, Corcoran, David, additional, Domingue, Benjamin, additional, Mitchell, Colter, additional, van Bergen, Elsje, additional, Boomsma, Dorret I., additional, Harris, Kathleen M., additional, Ip, Hill F., additional, Moffitt, Terrie E., additional, Poulton, Richie, additional, Prinz, Joseph, additional, Sugden, Karen, additional, Wertz, Jasmin, additional, Williams, Benjamin, additional, de Zeeuw, Eveline L., additional, Belsky, Daniel W., additional, Harden, K. Paige, additional, and Nivard, Michel G., additional

Published
2020
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18. Genetic Association Study of Childhood Aggression across raters, instruments and age

Author

Ip, Hill F., primary, van der Laan, Camiel M., additional, Krapohl, Eva M. L., additional, Brikell, Isabell, additional, Cristina, Sánchez-Mora, additional, Nolte, Ilja M., additional, St Pourcain, Beate, additional, Bolhuis, Koen, additional, Palviainen, Teemu, additional, Zafarmand, Hadi, additional, Colodro-Conde, Lucía, additional, Gordon, Scott, additional, Zayats, Tetyana, additional, Aliev, Fazil, additional, Jiang, Chang, additional, Wang, Carol A., additional, Saunders, Gretchen, additional, Karhunen, Ville, additional, Hammerschlag, Anke R., additional, Adkins, Daniel E., additional, Border, Richard, additional, Peterson, Roseann E., additional, Prinz, Joseph A., additional, Thiering, Elisabeth, additional, Seppälä, Ilkka, additional, Natàlia, Vilor-Tejedor, additional, Ahluwalia, Tarunveer S., additional, Day, Felix R., additional, Hottenga, Jouke-Jan, additional, Allegrini, Andrea G., additional, Rimfeld, Kaili, additional, Chen, Qi, additional, Lu, Yi, additional, Martin, Joanna, additional, Soler Artigas, María, additional, Rovira, Paula, additional, Bosch, Rosa, additional, Español, Gemma, additional, Ramos Quiroga, Josep Antoni, additional, Neumann, Alexander, additional, Ensink, Judith, additional, Grasby, Katrina, additional, Morosoli, José J., additional, Tong, Xiaoran, additional, Marrington, Shelby, additional, Middeldorp, Christel, additional, Scott, James G., additional, Vinkhuyzen, Anna, additional, Shabalin, Andrey A., additional, Corley, Robin, additional, Evans, Luke M., additional, Sugden, Karen, additional, Alemany, Silvia, additional, Sass, Lærke, additional, Vinding, Rebecca, additional, Ruth, Kate, additional, Tyrrell, Jess, additional, Davies, Gareth E., additional, Ehli, Erik A., additional, Hagenbeek, Fiona A., additional, De Zeeuw, Eveline, additional, Van Beijsterveldt, Toos C.E.M., additional, Larsson, Henrik, additional, Snieder, Harold, additional, Verhulst, Frank C., additional, Amin, Najaf, additional, Whipp, Alyce M., additional, Korhonen, Tellervo, additional, Vuoksimaa, Eero, additional, Rose, Richard J., additional, Uitterlinden, André G., additional, Heath, Andrew C., additional, Madden, Pamela, additional, Haavik, Jan, additional, Harris, Jennifer R., additional, Helgeland, Øyvind, additional, Johansson, Stefan, additional, Knudsen, Gun Peggy S., additional, Njolstad, Pal Rasmus, additional, Lu, Qing, additional, Rodriguez, Alina, additional, Henders, Anjali K., additional, Mamun, Abdullah, additional, Najman, Jackob M., additional, Brown, Sandy, additional, Hopfer, Christian, additional, Krauter, Kenneth, additional, Reynolds, Chandra, additional, Smolen, Andrew, additional, Stallings, Michael, additional, Wadsworth, Sally, additional, Wall, Tamara L., additional, Silberg, Judy L., additional, Miller, Allison, additional, Keltikangas-Järvinen, Liisa, additional, Hakulinen, Christian, additional, Pulkki-Råback, Laura, additional, Havdahl, Alexandra, additional, Magnus, Per, additional, Raitakari, Olli T., additional, Perry, John R.B., additional, Llop, Sabrina, additional, Lopez-Espinosa, Maria-Jose, additional, Bønnelykke, Klaus, additional, Bisgaard, Hans, additional, Sunyer, Jordi, additional, Lehtimäki, Terho, additional, Arseneault, Louise, additional, Standl, Marie, additional, Heinrich, Joachim, additional, Boden, Joseph, additional, Pearson, John, additional, Horwood, L John, additional, Kennedy, Martin, additional, Poulton, Richie, additional, Eaves, Lindon J., additional, Maes, Hermine H., additional, Hewitt, John, additional, Copeland, William E., additional, Costello, Elizabeth J., additional, Williams, Gail M., additional, Wray, Naomi, additional, Järvelin, Marjo-Riitta, additional, McGue, Matt, additional, Iacono, William, additional, Caspi, Avshalom, additional, Moffitt, Terrie E., additional, Whitehouse, Andrew, additional, Pennell, Craig E., additional, Klump, Kelly L., additional, Burt, S. Alexandra, additional, Dick, Danielle M., additional, Reichborn-Kjennerud, Ted, additional, Martin, Nicholas G., additional, Medland, Sarah E., additional, Vrijkotte, Tanja, additional, Kaprio, Jaakko, additional, Tiemeier, Henning, additional, Davey Smith, George, additional, Hartman, Catharina A., additional, Oldehinkel, Albertine J., additional, Casas, Miquel, additional, Ribasés, Marta, additional, Lichtenstein, Paul, additional, Lundström, Sebastian, additional, Plomin, Robert, additional, Bartels, Meike, additional, Nivard, Michel G., additional, and Boomsma, Dorret I., additional

Published
2019
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19. Using DNA From Mothers and Children to Study Parental Investment in Children’s Educational Attainment

Author

Wertz, Jasmin, primary, Moffitt, Terrie E., additional, Agnew‐Blais, Jessica, additional, Arseneault, Louise, additional, Belsky, Daniel W., additional, Corcoran, David L., additional, Houts, Renate, additional, Matthews, Timothy, additional, Prinz, Joseph A., additional, Richmond‐Rakerd, Leah S., additional, Sugden, Karen, additional, Williams, Benjamin, additional, and Caspi, Avshalom, additional

Published
2019
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20. From the clinic to the bench and back again in one dog year: identifying new treatments for sarcoma using a cross-species personalized medicine pipeline

Author

Rao, Sneha, primary, Somarelli, Jason A., additional, Altunel, Erdem, additional, Selmic, Laura E., additional, Byrum, Mark, additional, Sheth, Maya U., additional, Cheng, Serene, additional, Ware, Kathryn E., additional, Kim, So Young, additional, Prinz, Joseph A., additional, Devos, Nicolas, additional, Corcoran, David L., additional, Moseley, Arthur, additional, Soderblom, Erik, additional, Hsu, S. David, additional, and Eward, William C., additional

Published
2019
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21. Using DNA from mothers and children to study parental investment in children's educational attainment

Author

Wertz, Jasmin, primary, Moffitt, Terrie E., additional, Agnew-Blais, Jessica, additional, Arseneault, Louise, additional, Belsky, Daniel W., additional, Corcoran, David L., additional, Houts, Renate, additional, Matthews, Timothy, additional, Prinz, Joseph A., additional, Richmond-Rakerd, Leah S., additional, Sugden, Karen, additional, Williams, Benjamin, additional, and Caspi, Avshalom, additional

Published
2018
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22. A Polygenic Score for Higher Educational Attainment is Associated with Larger Brains

Author

Elliott, Maxwell L, primary, Belsky, Daniel W, additional, Anderson, Kevin, additional, Corcoran, David L, additional, Ge, Tian, additional, Knodt, Annchen, additional, Prinz, Joseph A, additional, Sugden, Karen, additional, Williams, Benjamin, additional, Ireland, David, additional, Poulton, Richie, additional, Caspi, Avshalom, additional, Holmes, Avram, additional, Moffitt, Terrie, additional, and Hariri, Ahmad R, additional

Published
2018
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23. Genetics & the Geography of Health, Behavior, and Attainment

Author

Belsky, Daniel W, primary, Caspi, Avshalom, additional, Arseneault, Louise, additional, Corcoran, David L, additional, Domingue, Benjamin W, additional, Harris, Kathleen Mullan, additional, Houts, Renate M, additional, Mill, Jonathan S, additional, Moffitt, Terrie E, additional, Prinz, Joseph, additional, Sugden, Karen, additional, Wertz, Jasmin, additional, Williams, Benjamin, additional, and Odgers, Candice L, additional

Published
2018
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24. A Polygenic Score for Higher Educational Attainment is Associated with Larger Brains

Author

Elliott, Maxwell L., primary, Belsky, Daniel W, additional, Anderson, Kevin, additional, Corcoran, David L., additional, Ge, Tian, additional, Knodt, Annchen, additional, Prinz, Joseph A., additional, Sugden, Karen, additional, Williams, Benjamin, additional, Ireland, David, additional, Poulton, Richie, additional, Caspi, Avshalom, additional, Holmes, Avram, additional, Moffitt, Terrie, additional, and Hariri, Ahmad R, additional

Published
2018
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25. Identification of functional elements and regulatory circuits by Drosophila modENCODE

Author

Roy, Sushmita, Ernst, Jason, Kharchenko, Peter V., Kheradpour, Pouya, Negre, Nicolas, Eaton, Matthew L., Landolin, Jane M., Bristow, Christopher A., Ma, Lijia, Lin, Michael F., Washietl, Stefan, Arshinoff, Bradley I., Ay, Ferhat, Meyer, Patrick E., Robine, Nicolas, Washington, Nicole L., Di Stefano, Luisa, Berezikov, Eugene, Brown, Christopher D., Candeias, Rogerio, Carlson, Joseph W., Carr, Adrian, Jungreis, Irwin, Marbach, Daniel, Sealfon, Rachel, Tolstorukov, Michael Y., Will, Sebastian, Alekseyenko, Artyom A., Artieri, Carlo, Booth, Benjamin W., Brooks, Angela N., Dai, Qi, Davis, Carrie A., Duff, Michael O., Feng, Xin, Gorchakov, Andrey A., Gu, Tingting, Henikoff, Jorja G., Kapranov, Philipp, Li, Renhua, MacAlpine, Heather K., Malone, John, Minoda, Aki, Nordman, Jared, Okamura, Katsutomo, Perry, Marc, Powell, Sara K., Riddle, Nicole C., Sakai, Akiko, Samsonova, Anastasia A., Sandler, Jeremy E., Schwartz, Yuri B., Sher, Noa, Spokony, Rebecca, Sturgill, David, van Baren, Marijke, Wan, Kenneth H., Yang, Li, Yu, Charles, Feingold, Elise, Good, Peter, Guyer, Mark, Lowdon, Rebecca, Ahmad, Kami, Andrews, Justen, Berger, Bonnie, Brenner, Steven E., Brent, Michael R., Cherbas, Lucy, Elgin, Sarah C.R., Gingeras, Thomas R., Grossman, Robert, Hoskins, Roger A., Kaufman, Thomas C., Kent, William, Kuroda, Mitzi I., Orr-Weaver, Terry, Perrimon, Norbert, Pirrotta, Vincenzo, Posakony, James W., Ren, Bing, Russell, Steven, Cherbas, Peter, Graveley, Brenton R., Lewis, Suzanna, Micklem, Gos, Oliver, Brian, Park, Peter J., Celniker, Susan E., Henikoff, Steven, Karpen, Gary H., Lai, Eric C., MacAlpine, David M., Stein, Lincoln D., White, Kevin P., Kellis, Manolis, Booth, Benjamin, Comstock, Charles L.G., Dobin, Alex, Drenkow, Jorg, Dudoit, Sandrine, Dumais, Jacqueline, Fagegaltier, Delphine, Ghosh, Srinka, Hansen, Kasper D., Jha, Sonali, Langton, Laura, Lin, Wei, Miller, David, Tenney, Aaron E., Wang, Huaien, Willingham, Aarron T., Zaleski, Chris, Zhang, Dayu, Acevedo, David, Bishop, Eric P., Gadel, Sarah E., Jung, Youngsook L., Kennedy, Cameron D., Lee, Ok Kyung, Linder-Basso, Daniela, Marchetti, Sarah E., Shanower, Gregory, Nègre, Nicolas, Grossman, Robert L., Auburn, Richard, Bellen, Hugo J., Chen, Jia, Domanus, Marc H., Hanley, David, Heinz, Elizabeth, Li, Zirong, Meyer, Folker, Miller, Steven W., Morrison, Carolyn A., Scheftner, Douglas A., Senderowicz, Lionel, Shah, Parantu K., Suchy, Sarah, Tian, Feng, Venken, Koen J.T., White, Robert, Wilkening, Jared, Zieba, Jennifer, Nordman, Jared T., Orr-Weaver, Terry L., DeNapoli, Leyna C., Ding, Queying, Eng, Thomas, Kashevsky, Helena, Li, Sharon, Prinz, Joseph A., Hannon, Gregory J., Hirst, Martin, Marra, Marco, Rooks, Michelle, Zhao, Yongjun, Bryson, Terri D., Perry, Marc D., Kent, William J., Lewis, Suzanna E., Barber, Galt, Chateigner, Aurelien, Clawson, Hiram, Contrino, Sergio, Guillier, Francois, Hinrichs, Angie S., Kephart, Ellen T., Lloyd, Paul, Lyne, Rachel, McKay, Sheldon, Moore, Richard A., Mungall, Chris, Rutherford, Kim M., Ruzanov, Peter, Smith, Richard, Stinson, E. O., Zha, Zheng, Artieri, Carlo G., Malone, John H., Jiang, Lichun, Mattiuzzo, Nicolas, Feingold, Elise A., Good, Peter J., Guyer, Mark S., Lowdon, Rebecca F., Stem Cell Aging Leukemia and Lymphoma (SALL), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)

Subjects
Transcription, Genetic, Genome, Insect, Gene regulatory network, Genomics, Genes, Insect, Computational biology, Biology, Genome, Article, Epigenesis, Genetic, Histones, Nucleosome, Animals, Drosophila Proteins, Gene Regulatory Networks, Promoter Regions, Genetic, Gene, Genetics, Multidisciplinary, Binding Sites, REDfly, Computational Biology, Molecular Sequence Annotation, Chromatin, Nucleosomes, Drosophila melanogaster, Gene Expression Regulation, RNA, Small Untranslated, Drosophila Protein, Transcription Factors
Abstract

From Genome to Regulatory Networks For biologists, having a genome in hand is only the beginning—much more investigation is still needed to characterize how the genome is used to help to produce a functional organism (see the Perspective by Blaxter ). In this vein, Gerstein et al. (p. 1775 ) summarize for the Caenorhabditis elegans genome, and The modENCODE Consortium (p. 1787 ) summarize for the Drosophila melanogaster genome, full transcriptome analyses over developmental stages, genome-wide identification of transcription factor binding sites, and high-resolution maps of chromatin organization. Both studies identified regions of the nematode and fly genomes that show highly occupied targets (or HOT) regions where DNA was bound by more than 15 of the transcription factors analyzed and the expression of related genes were characterized. Overall, the studies provide insights into the organization, structure, and function of the two genomes and provide basic information needed to guide and correlate both focused and genome-wide studies.

Published
2010

26. Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

Author

Belsky, Daniel W., primary, Moffitt, Terrie E., additional, Cohen, Alan A., additional, Corcoran, David L., additional, Levine, Morgan E., additional, Prinz, Joseph A., additional, Schaefer, Jonathan, additional, Sugden, Karen, additional, Williams, Benjamin, additional, Poulton, Richie, additional, and Caspi, Avshalom, additional

Published
2017
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28. Rare Codons Regulate KRas Oncogenesis

Author

Lampson, Benjamin L., Pershing, Nicole L.K., Prinz, Joseph A., Lacsina, Joshua R., Marzluff, William F., Nicchitta, Christopher V., MacAlpine, David M., and Counter, Christopher M.

Published
2013
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29. Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?

Author

Belsky, Daniel W., Moffitt, Terrie E., Cohen, Alan A., Corcoran, David L., Levine, Morgan E., Prinz, Joseph A., Schaefer, Jonathan, Sugden, Karen, Williams, Benjamin, Poulton, Richie, and Caspi, Avshalom

Subjects
AGING, PSYCHOLOGICAL aspects of aging, BIOMARKERS, COGNITION disorders, PHOSPHATES, PHYSICAL diagnosis, TELOMERES, GENOMICS, REPEATED measures design, EPIGENOMICS
Abstract

The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "geroprotective" therapies in humans, outcome measures are needed that can assess extension of disease-free life span. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented 7 methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study (New Zealand; persons born 1972-1973). We studied 11 measures in total: telomere-length and erosion, 3 epigenetic-clocks and their ticking rates, and 3 biomarker-composites. Contrary to expectation, we found low agreement between different measures of biological aging. We next compared associations between biological aging measures and outcomes that geroprotective therapies seek to modify: physical functioning, cognitive decline, and subjective signs of aging, including aged facial appearance. The 71-cytosine-phosphateguanine epigenetic clock and biomarker composites were consistently related to these aging-related outcomes. However, effect sizes were modest. Results suggested that various proposed approaches to quantifying biological aging may not measure the same aspects of the aging process. Further systematic evaluation and refinement of measures of biological aging is needed to furnish outcomes for geroprotector trials. [ABSTRACT FROM AUTHOR]

Published
2018
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33. Pre-replication complex proteins assemble at regions of low nucleosome occupancy within the Chinese hamster dihydrofolate reductase initiation zone

Author

Lubelsky, Yoav, primary, Sasaki, Takayo, additional, Kuipers, Marjorie A., additional, Lucas, Isabelle, additional, Le Beau, Michelle M., additional, Carignon, Sandra, additional, Debatisse, Michelle, additional, Prinz, Joseph A., additional, Dennis, Jonathan H., additional, and Gilbert, David M., additional

Published
2010
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36. Hadarim: A Description and Evaluation of a School-Based Adlerian Parenting Program in Israel.

Author

Prinz, Joseph, Arkin, Sharon, and Gelkopf, Marc

Subjects
*ADLERIAN psychology, *PARENTING, *PARENTS, *TEACHERS, *PARENT-child relationships
Abstract

Parental guidance has been central to the Adlerian movement from its inception and has been provided in many formats and settings by all manner of trainers. The authors describe an innovative teacher-administered parenting program developed and implemented by the Ministry of Education of Israel which changes communication patterns and relationships in the homes of participants and transforms the classroom culture of participants' children. They explain the philosophical and theoretical underpinnings, organization, and content of the Hadarim program. Results of an evaluation conducted at 4 elementary schools indicate that the program improved the parenting and educational skills of both teachers and parents. [ABSTRACT FROM AUTHOR]

Published
2008

37. Adlerian group therapy with substance abusers.

Author

Prinz, Joseph and Arkin, Sharon

Subjects
*GROUP psychotherapy, *SUBSTANCE abuse & psychology
Abstract

Describes Adlerian ideas as applied to substance abuse and codependency treatment programs. Treatment philosophy-respect, responsibility, responsiveness and resourcefulness; Working as co-therapists; Life-style, personality priorities, and purposes for drinking. `Behind the back' technique.

Published
1994

38. Alcoholics and their treatment: Current Adlerian thinking.

Author

Prinz, Joseph (Yosi)

Subjects
*ALCOHOLISM treatment
Abstract

Studies the lifestyle and treatment methods appropriate for alcoholics. Disease concept of alcoholism; Characteristics, goals and behaviors of alcoholics; Implications for treatment; Self-determination and powerlessness; Applicable Adlerian principles; Alcoholic's guilt feelings; Psychotherapy; Treatment approach, methods and techniques; Author's interpretations and recommendations.

Published
1993

49. Chromatin signatures of the Drosophila replication program.

Author

Eaton, Matthew L., Prinz, Joseph A., MacAlpine, Heather K., Tretyakov, George, Kharchenko, Peter V., and MacAlpine, David M.

Subjects
*DNA replication, *DROSOPHILA, *GENOMES, *GENES, *CHROMATIN
Abstract

DNA replication initiates from thousands of start sites throughout the Drosophila genome and must be coordinated with other ongoing nuclear processes such as transcription to ensure genetic and epigenetic inheritance. Considerable progress has been made toward understanding how chromatin modifications regulate the transcription program; in contrast, we know relatively little about the role of the chromatin landscape in defining how start sites of DNA replication are selected and regulated. Here, we describe the Drosophila replication program in the context of the chromatin and transcription landscape for multiple cell lines using data generated by the modENCODE consortium. We find that while the cell lines exhibit similar replication programs, there are numerous cell line-specific differences that correlate with changes in the chromatin architecture. We identify chromatin features that are associated with replication timing, early origin usage, and ORC binding. Primary sequence, activating chromatin marks, and DNA-binding proteins (including chromatin remodelers) contribute in an additive manner to specify ORC-binding sites. We also generate accurate and predictive models from the chromatin data to describe origin usage and strength between cell lines. Multiple activating chromatin modifications contribute to the function and relative strength of replication origins, suggesting that the chromatin environment does not regulate origins of replication as a simple binary switch, but rather acts as a tunable rheostat to regulate replication initiation events. [ABSTRACT FROM AUTHOR]

Published
2011
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50. A Polygenic Score for Higher Educational Attainment is Associated with Larger Brains.

Author

Elliott ML, Belsky DW, Anderson K, Corcoran DL, Ge T, Knodt A, Prinz JA, Sugden K, Williams B, Ireland D, Poulton R, Caspi A, Holmes A, Moffitt T, and Hariri AR

Subjects
Adolescent, Adult, Aged, Brain anatomy & histology, Female, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multifactorial Inheritance, New Zealand, Organ Size, United Kingdom, United States, Young Adult, Brain diagnostic imaging, Cognition, Educational Status, Intelligence genetics
Abstract

People who score higher on intelligence tests tend to have larger brains. Twin studies suggest the same genetic factors influence both brain size and intelligence. This has led to the hypothesis that genetics influence intelligence partly by contributing to the development of larger brains. We tested this hypothesis using four large imaging genetics studies (combined N = 7965) with polygenic scores derived from a genome-wide association study (GWAS) of educational attainment, a correlate of intelligence. We conducted meta-analysis to test associations among participants' genetics, total brain volume (i.e., brain size), and cognitive test performance. Consistent with previous findings, participants with higher polygenic scores achieved higher scores on cognitive tests, as did participants with larger brains. Participants with higher polygenic scores also had larger brains. We found some evidence that brain size partly mediated associations between participants' education polygenic scores and their cognitive test performance. Effect sizes were larger in the population-based samples than in the convenience-based samples. Recruitment and retention of population-representative samples should be a priority for neuroscience research. Findings suggest promise for studies integrating GWAS discoveries with brain imaging to understand neurobiology linking genetics with cognitive performance., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Published
2019
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