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1. Do participants in genome sequencing studies of psychiatric disorders wish to be informed of their results? A survey study.

Author

Elise T Bui, Natalie K Anderson, Layla Kassem, and Francis J McMahon

Subjects
Medicine, Science
Abstract

As large-scale genome sequencing technology advances, concerns surrounding the reporting of individual findings to study volunteers have grown and fueled controversy. This is especially true in mental health research, where the clinical importance of sequencing results is particularly unclear. The ethical, legal, and social issues are being widely debated, but less is known about the attitudes of actual study volunteers toward sequencing studies or what they wish to learn about their DNA sequence and its health implications. This study provides information on psychiatric research volunteers' attitudes, beliefs, and concerns with respect to participation in DNA sequencing studies and reporting of individual results.We conducted a pilot study using a questionnaire that we developed to assess what information volunteers in an ongoing family study of bipolar disorder would like to receive if they underwent genome sequencing, what they would do with that information, and what concerns they may have.Almost all of the respondents were willing to participate in genome sequencing. Most respondents wished to be informed about all their health-related genetic risks, including risks for diseases without known prevention or treatment. However, few respondents felt well informed about the nature of genome sequencing or its implications for their health, insurability, or offspring.Despite generally positive attitudes toward genome sequencing among study volunteers, most are not fully aware of the special issues raised by genome sequencing. The attitudes of study volunteers should be considered in the debate about the reporting of individual findings from genome sequencing.

Published
2014
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2. Generalization of evaluative conditioning toward foods: Increasing sensitivity to health in eating intentions

Author

Russell H. Fazio and Elise T. Bui

Subjects
Adult, Male, Taste, 050109 social psychology, Intention, Models, Psychological, 050105 experimental psychology, Eating, Food Preferences, Young Adult, Generalization (learning), Conditioning, Psychological, Food choice, Humans, 0501 psychology and cognitive sciences, Misattribution of memory, Evaluative conditioning, Applied Psychology, digestive, oral, and skin physiology, 05 social sciences, Feeding Behavior, Psychiatry and Mental health, Attitude, Categorization, Conditioning, Female, Attitude change, Psychology, Social psychology
Abstract

OBJECTIVE Evaluative conditioning (EC), the pairing of objects (conditioned stimuli; CS) with positive and negative unconditioned stimuli (US) in order to induce attitude change, has proven to be a viable method of changing attitudes toward foods and corresponding eating behaviors. Positively conditioning healthy foods and negatively conditioning unhealthy foods should result in healthier food choices. Of interest in the current research is the extent to which EC can generalize beyond the conditioned foods to entire dimensions underlying food judgment, such as health and taste. METHOD The current research included 2 EC experiments configured in accord with the Implicit Misattribution Model (IMM; Jones, Fazio, & Olson, 2009). Four healthy CS foods were paired with positive US and 4 unhealthy CS foods were paired with negative US. Participants then reported eating intentions for a variety of foods, including non-CS foods. RESULTS Experiment 1 demonstrated that conditioning a few exemplar food items increased sensitivity to health and decreased sensitivity to taste when judging a variety of additional foods. Experiment 2 replicated the generalization effect with regard to health sensitivity, but only when a task that preceded the EC procedure promoted, rather than interfered with, categorization of the CS foods by health. CONCLUSIONS This research shows that EC can generalize to an entire dimension underlying food judgment and that this effect is facilitated by accessibility of the health dimension at the time of exposure to the EC pairings. (PsycINFO Database Record

Published
2016
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3. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

Author

Christina M. Hultman, Peter R. Schofield, J. Raymond DePaulo, Martin Alda, Szabolcs Szelinger, Susanne Bengesser, Stefan Herms, Alessio Squassina, Gustavo Turecki, Barbara König, Fabian Streit, Jana Strohmaier, Martin Schalling, Maren Lang, Michael McCarthy, Per Hoffmann, Sarah K. Tighe, William Byerley, Jean-Pierre Kahn, Bárbara Arias, Alfonso Tortorella, Francis J. McMahon, William Lawson, Gonzalo Laje, Wade H. Berrettini, Tatyana Shekhtman, Jean-Michel Aubry, Erin N. Smith, Peng Zhang, Stefanie Heilmann-Heimbach, Evaristus A. Nwulia, Thomas B. Barrett, Cinnamon S. Bloss, Nicholas J. Schork, Tatiana Foroud, Antonio Benabarre, Bernhard T. Baune, William Coryell, Giovanni Severino, Sébastien Gard, Michael Bauer, Layla Kassem, Judith A. Badner, Peter P. Zandi, Rebecca McKinney, Paul D. Shilling, Mazda Adli, Pablo Cervantes, John P. Rice, Nirmala Akula, Marcella Rietschel, Maria Grigoroiu-Serbanescu, Armin Birner, David Craig, Caterina Chillotti, Sebastian Kliwicki, Guy A. Rouleau, Alexandre Dayer, Claire Slaney, Thomas Stamm, Piotr M. Czerski, Pamela B. Mahon, Elliot S. Gershon, Susan L. McElroy, Andreas J. Forstner, Sarah E. Bergen, Peter Propping, Johannes Schumacher, Mikael Landén, Marion Leboyer, Janusz K. Rybakowski, Cristiana Cruceanu, Urs Heilbronner, Joanna Hauser, Fernando S. Goes, Howard J. Edenberg, Markus M. Nöthen, Adam Wright, Chunyu Liu, Daniel L. Koller, James B. Potash, Elise T. Bui, Julie Garnham, Caroline M. Nievergelt, William A. Scheftner, Lina Martinsson, Janice M. Fullerton, Maria Del Zompo, Shashi Hitturlingappa, Mirko Manchia, Andreas Reif, Andrea Pfennig, Thomas G. Schulze, Eduard Vieta, Jie Song, Liping Hou, Maria Hipolito, John I. Nurnberger, Louise Frisén, Anna Maaser, Wolfgang Maier, Thomas W. Mühleisen, Andrea Hofmann, Philip B. Mitchell, Clara Brichant-Petitjean, Raffaella Ardau, Joanna M. Biernacka, N. Lackner, Eva Z. Reininghaus, Francesc Colom, Catharina Lavebratt, Francis M. Mondimore, Urban Ösby, Esther Jiménez, Abesh Kumar Bhattacharjee, Marina Mitjans, Tiffany A. Greenwood, Peter Falkai, Stephanie H. Witt, Stéphane Jamain, Sven Cichon, Julia Volkert, Bruno Etain, Lena Backlund, Tomas Novak, Sarah Kittel-Schneider, Franziska Degenhardt, Barbara W. Schweizer, Mark A. Frye, Christian Simhandl, John R. Kelsoe, Sebastian Zöllner, Frank Bellivier, Palmiero Monteleone, Tony Davis, Susan G. Leckband, Mario Maj, Melvin G. McInnis, and Pavla Stopkova

Subjects
Genetics, 0303 health sciences, Genome-wide association study, Odds ratio, Biology, Heritability, medicine.disease, Mental illness, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Intergenic region, Mood, medicine, Bipolar disorder, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10−9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10−9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.

Published
2016
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4. Genetic variants associated with response to lithium treatment in bipolar disorder:a genome-wide association study

Author

Ryota Hashimoto, Andrea Hofmann, Gustavo Turecki, N. Lackner, Philip B. Mitchell, Bárbara Arias, Urban Ösby, J. Raymond DePaulo, Martin Alda, Julie Garnham, Esther Jiménez, Abesh Kumar Bhattacharjee, Peter P. Zandi, Clara Brichant-Petitjean, Frank Bellivier, Marina Mitjans, Palmiero Monteleone, Eduard Vieta, Liping Hou, Eva Z. Reininghaus, Raffaella Ardau, Paul D. Shilling, Mazda Adli, Armin Birner, Marion Leboyer, Lena Backlund, Andreas J. Forstner, David A. Cousins, Francesc Colom, Catharina Lavebratt, K Oliver Schubert, Barbara W. Schweizer, Mario Maj, Kazufumi Akiyama, Antoni Benabarre, Julia Volkert, Alessio Squassina, Marcella Rietschel, Stephanie H. Witt, Gonzalo Laje, Louise Frisén, Jordan W. Smoller, Paul Grof, Tomas Novak, L. Trevor Young, Sven Cichon, Bruno Etain, Ichiro Kusumi, Sarah K. Tighe, Sarah Kittel-Schneider, Florian Seemüller, Jean-Pierre Kahn, Markus M. Nöthen, Tadafumi Kato, Alexandre Dayer, Caroline M. Nievergelt, Mirko Manchia, Francis J. McMahon, Peter R. Schofield, Susanne Bengesser, Po-Hsiu Kuo, Stefan Herms, Scott R. Clark, Piotr M. Czerski, Oliver Gruber, Franziska Degenhardt, Mark A. Frye, Joanna M. Biernacka, Christian Simhandl, Guo-Bo Chen, Adam Wright, Sébastien Gard, Peter Falkai, Carlos Jaramillo, Stéphane Jamain, Roy H. Perlis, Andrea Pfennig, Tatyana Shekhtman, Maria Del Zompo, Clarissa de Rosalmeida Dantas, Thomas G. Schulze, Alfonso Tortorella, Francis M. Mondimore, John R. Kelsoe, Jean-Michel Aubry, Mikael Landén, Andreas Reif, Naomi R. Wray, Martin Schalling, Janice M. Fullerton, Nirmala Akula, Claudio E. M. Banzato, Elise T. Bui, Per Hoffmann, Sebastian Kliwicki, Guy A. Rouleau, Maria Grigoroiu-Serbanescu, Glenda MacQueen, Lina Martinsson, Giovanni Severino, Norio Ozaki, Daniela Reich-Erkelenz, Layla Kassem, Manuel Mattheisen, Pavla Stopkova, Michael Bauer, Caterina Chillotti, Kazutaka Shimoda, Bernhard T. Baune, Janusz K. Rybakowski, Thomas Stamm, Joanna Hauser, Fernando S. Goes, Urs Heilbronner, James B. Potash, Susan L. McElroy, Barbara König, Susan G. Leckband, Michael McCarthy, Hsi-Chung Chen, Claire Slaney, Cristiana Cruceanu, Pablo Cervantes, Hou, Liping, Heilbronner, Ur, Degenhardt, Franziska, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Ardau, Raffaella, Arias, Bárbara, Backlund, Lena, Banzato, Claudio E M, Benabarre, Antoni, Bengesser, Susanne, Bhattacharjee, Abesh Kumar, Biernacka, Joanna M, Birner, Armin, Brichant-Petitjean, Clara, Bui, Elise T, Cervantes, Pablo, Chen, Guo-Bo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Colom, Francesc, Cousins, David A, Cruceanu, Cristiana, Czerski, Piotr M, Dantas, Clarissa R, Dayer, Alexandre, Étain, Bruno, Falkai, Peter, Forstner, Andreas J, Frisén, Louise, Fullerton, Janice M, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grof, Paul, Gruber, Oliver, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Jaramillo, Carlos A López, Macqueen, Glenda, Manchia, Mirko, Martinsson, Lina, Mattheisen, Manuel, Mccarthy, Michael J, Mcelroy, Susan L, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Ösby, Urban, Ozaki, Norio, Perlis, Roy H, Pfennig, Andrea, Reich-Erkelenz, Daniela, Rouleau, Guy A, Schofield, Peter R, Schubert, K Oliver, Schweizer, Barbara W, Seemüller, Florian, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Kazutaka, Simhandl, Christian, Slaney, Claire M, Smoller, Jordan W, Squassina, Alessio, Stamm, Thoma, Stopkova, Pavla, Tighe, Sarah K, Tortorella, Alfonso, Turecki, Gustavo, Volkert, Julia, Witt, Stephanie, Wright, Adam, Young, L Trevor, Zandi, Peter P, Potash, James B, Depaulo, J Raymond, Bauer, Michael, Reininghaus, Eva Z, Novák, Toma, Aubry, Jean-Michel, Maj, Mario, Baune, Bernhard T, Mitchell, Philip B, Vieta, Eduard, Frye, Mark A, Rybakowski, Janusz K, Kuo, Po-Hsiu, Kato, Tadafumi, Grigoroiu-Serbanescu, Maria, Reif, Andrea, Del Zompo, Maria, Bellivier, Frank, Schalling, Martin, Wray, Naomi R, Kelsoe, John R, Alda, Martin, Rietschel, Marcella, Mcmahon, Francis J, and Schulze, Thomas G

Subjects
Male, Glial Cell Line-Derived Neurotrophic Factor Receptors, Bipolar Disorder, Genotype, Genome-wide association study, Single-nucleotide polymorphism, Bipolar Disorder/drug therapy/genetics, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, ddc:616.89, 0302 clinical medicine, Genetic variation, Medicine, Humans, Bipolar disorder, Prospective Studies, Allele, Polymorphism, Lithium Compounds/therapeutic use, Genetics, business.industry, Medicine (all), Genetic Variation, General Medicine, Single Nucleotide, Middle Aged, medicine.disease, Polymorphism, Single Nucleotide/genetics, 030227 psychiatry, 3. Good health, Phenotype, Treatment Outcome, Female, Genome-Wide Association Study, Lithium Compounds, business, 030217 neurology & neurosurgery, Imputation (genetics), Pharmacogenetics, Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics
Abstract

BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis.FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0).INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings.FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.

Published
2016
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5. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

Author

Philip B. Mitchell, Clara Brichant-Petitjean, Raffaella Ardau, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Sebastian Zöllner, Christina M. Hultman, Shashi Hitturlingappa, Maria Hipolito, Louise Frisén, Thomas W. Mühleisen, Layla Kassem, Christian Simhandl, Urban Ösby, Frank Bellivier, Peter Falkai, Alessio Squassina, Jana Strohmaier, Esther Jiménez, Palmiero Monteleone, Caterina Chillotti, Stéphane Jamain, Peter P. Zandi, Abesh Kumar Bhattacharjee, Tony Davis, Sarah K. Tighe, William Byerley, Jean-Pierre Kahn, Michael Bauer, Nicholas J. Schork, Joanna Hauser, Andreas J. Forstner, Francis J. McMahon, Peter Propping, Marina Mitjans, Tiffany A. Greenwood, Alfonso Tortorella, Fernando S. Goes, Szabolcs Szelinger, Tomas Novak, Erin N. Smith, Andrea Pfennig, Susan G. Leckband, Pablo Cervantes, Sarah Kittel-Schneider, Sébastien Gard, Adam Wright, Tatiana Foroud, Joanna M. Biernacka, Jean-Michel Aubry, Marcella Rietschel, Elliot S. Gershon, Janusz K. Rybakowski, John R. Kelsoe, Stephanie H. Witt, Elise T. Bui, Sarah E. Bergen, Tatyana Shekhtman, Thomas G. Schulze, Sven Cichon, Julia Volkert, Thomas Stamm, Eduard Vieta, Jie Song, Liping Hou, Markus M. Nöthen, Bruno Etain, Mikael Landén, Caroline M. Nievergelt, Mirko Manchia, William Coryell, Howard J. Edenberg, Andreas Reif, Urs Heilbronner, Gonzalo Laje, Lena Backlund, Wade H. Berrettini, Martin Schalling, Franziska Degenhardt, Susan L. McElroy, Mario Maj, Francis M. Mondimore, Peng Zhang, Stefanie Heilmann-Heimbach, Janice M. Fullerton, Daniel L. Koller, James B. Potash, Michael McCarthy, Barbara W. Schweizer, Rebecca McKinney, Nirmala Akula, Sebastian Kliwicki, Guy A. Rouleau, N. Lackner, William Lawson, Melvin G. McInnis, Eva Z. Reininghaus, Maria Grigoroiu-Serbanescu, Pavla Stopkova, Francesc Colom, Catharina Lavebratt, Judith A. Badner, Mark A. Frye, Alexandre Dayer, Giovanni Severino, Maren Lang, John P. Rice, Per Hoffmann, William A. Scheftner, Lina Martinsson, Pamela B. Mahon, Piotr M. Czerski, Paul D. Shilling, Mazda Adli, Armin Birner, David Craig, Gustavo Turecki, Bárbara Arias, Evaristus A. Nwulia, Thomas B. Barrett, Cinnamon S. Bloss, Marion Leboyer, Chunyu Liu, Maria Del Zompo, Antonio Benabarre, Bernhard T. Baune, Fabian Streit, John I. Nurnberger, Barbara König, Anna Maaser, Wolfgang Maier, Julie Garnham, Claire Slaney, Johannes Schumacher, Cristiana Cruceanu, J. Raymond DePaulo, Martin Alda, Andrea Hofmann, Hou, Liping, Bergen, Sarah E., Akula, Nirmala, Song, Jie, Hultman, Christina M., Landén, Mikael, Adli, Mazda, Alda, Martin, Ardau, Raffaella, Arias, Barbara, Aubry, Jean-Michel, Backlund, Lena, Badner, Judith A., Barrett, Thomas B., Bauer, Michael, Baune, Bernhard T., Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Berrettini, Wade H., Bhattacharjee, Abesh Kumar, Biernacka, Joanna M., Birner, Armin, Bloss, Cinnamon S., Brichant-Petitjean, Clara, Bui, Elise T., Byerley, William, Cervantes, Pablo, Chillotti, Caterina, Cichon, Sven, Colom, Francesc, Coryell, William, Craig, David W., Cruceanu, Cristiana, Czerski, Piotr M., Davis, Tony, Dayer, Alexandre, Degenhardt, Franziska, Del Zompo, Maria, Depaulo, J. Raymond, Edenberg, Howard J., Étain, Bruno, Falkai, Peter, Foroud, Tatiana, Forstner, Andreas J., Frisén, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Gershon, Elliot S., Goes, Fernando S., Greenwood, Tiffany A., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Heilbronner, Ur, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hipolito, Maria, Hitturlingappa, Shashi, Hoffmann, Per, Hofmann, Andrea, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kelsoe, John R., Kittel-Schneider, Sarah, Kliwicki, Sebastian, Koller, Daniel L., König, Barbara, Lackner, Nina, Laje, Gonzalo, Lang, Maren, Lavebratt, Catharina, Lawson, William B., Leboyer, Marion, Leckband, Susan G., Liu, Chunyu, Maaser, Anna, Mahon, Pamela B., Maier, Wolfgang, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael J., Mcelroy, Susan L., Mcinnis, Melvin G., Mckinney, Rebecca, Mitchell, Philip B., Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Mühleisen, Thomas W., Nievergelt, Caroline M., Nöthen, Markus M., Novák, Toma, Nurnberger, John I., Nwulia, Evaristus A., Ösby, Urban, Pfennig, Andrea, Potash, James B., Propping, Peter, Reif, Andrea, Reininghaus, Eva, Rice, John, Rietschel, Marcella, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Scheftner, William A., Schofield, Peter R., Schork, Nicholas J., Schulze, Thomas G., Schumacher, Johanne, Schweizer, Barbaraw., Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D., Simhandl, Christian, Slaney, Claire M., Smith, Erin N., Squassina, Alessio, Stamm, Thoma, Stopkova, Pavla, Streit, Fabian, Strohmaier, Jana, Szelinger, Szabolc, Tighe, Sarah K., Tortorella, Alfonso, Turecki, Gustavo, Vieta, Eduard, Volkert, Julia, Witt, Stephanie H., Wright, Adam, Zandi, Peter P., Zhang, Peng, Zollner, Sebastian, and Mcmahon, Francis J.

Subjects
Male, 0301 basic medicine, Bipolar Disorder, Receptor, ErbB-2, Genome-wide association study, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, ddc:616.89, 0302 clinical medicine, Genetic, Molecular Biology, Genetics, Genetics (clinical), medicine, Humans, Bipolar disorder, Genetic association, Chromosomes, Human, X, Association Studies Articles, Case-control study, General Medicine, Odds ratio, Heritability, medicine.disease, 3. Good health, 030104 developmental biology, Meta-analysis, Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 × 10 (-) (9); odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 × 10 (-) (9); OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.

Published
2016

6. Do participants in genome sequencing studies of psychiatric disorders wish to be informed of their results? A survey study

Author

Layla Kassem, Natalie K. Anderson, Elise T. Bui, and Francis J. McMahon

Subjects
medicine.medical_specialty, Clinical Research Design, Decision Making, MEDLINE, lcsh:Medicine, Genetic Counseling, Pilot Projects, Social issues, Research and Analysis Methods, Genome, DNA sequencing, Ethics, Research, Genomic Medicine, Surveys and Questionnaires, Mental Health and Psychiatry, Genetics, Medicine and Health Sciences, Medicine, Psychology, Humans, Bipolar disorder, Genetic Testing, Genome Sequencing, Psychiatry, Molecular Biology Techniques, Sequencing Techniques, lcsh:Science, Molecular Biology, Clinical Genetics, Research ethics, Multidisciplinary, Survey Research, business.industry, Genome, Human, Mental Disorders, lcsh:R, Personalized Medicine, Biology and Life Sciences, Human Genetics, Genomics, Sequence Analysis, DNA, medicine.disease, Mental health, Research Design, Human genome, lcsh:Q, business, Research Article
Abstract

Objective: As large-scale genome sequencing technology advances, concerns surrounding the reporting of individual findings to study volunteers have grown and fueled controversy. This is especially true in mental health research, where the clinical importance of sequencing results is particularly unclear. The ethical, legal, and social issues are being widely debated, but less is known about the attitudes of actual study volunteers toward sequencing studies or what they wish to learn about their DNA sequence and its health implications. This study provides information on psychiatric research volunteers’ attitudes, beliefs, and concerns with respect to participation in DNA sequencing studies and reporting of individual results. Method: We conducted a pilot study using a questionnaire that we developed to assess what information volunteers in an ongoing family study of bipolar disorder would like to receive if they underwent genome sequencing, what they would do with that information, and what concerns they may have. Results: Almost all of the respondents were willing to participate in genome sequencing. Most respondents wished to be informed about all their health-related genetic risks, including risks for diseases without known prevention or treatment. However, few respondents felt well informed about the nature of genome sequencing or its implications for their health, insurability, or offspring. Conclusions: Despite generally positive attitudes toward genome sequencing among study volunteers, most are not fully aware of the special issues raised by genome sequencing. The attitudes of study volunteers should be considered in the debate about the reporting of individual findings from genome sequencing.

Published
2014

7. The International Consortium on Lithium Genetics (ConLiGen): An Initiative by the NIMH and IGSLI to Study the Genetic Basis of Response to Lithium Treatment

Author

Thomas G. Schulze, L. Trevor Young, Layla Kassem, Paola Piccardi, Andrea Pfennig, Caterina Chillotti, Raffaella Ardau, Paul Grof, Oliver Gruber, Michael Bauer, Ichiro Kusumi, Johannes Schumacher, Sven Cichon, Nakao Iwata, Mazda Adli, Janusz K. Rybakowski, Glenda MacQueen, Maria Del Zompo, Elise T. Bui, Susan G. Leckband, Giovanni Severino, Jordan W. Smoller, Sarah Kittel-Schneider, Sevilla D. Detera-Wadleigh, Gonzalo Laje, Norio Ozaki, Piotr M. Czerski, Andreas Reif, Takeo Yoshikawa, Ryota Hashimoto, Gustavo Turecki, Mirko Manchia, Martin Alda, Nirmala Akula, Sebastian Kliwicki, Guy A. Rouleau, Joanna Hauser, John R. Kelsoe, Johanna Sasse, Alessio Squassina, Francis J. McMahon, Rebecca Hoban, Roy H. Perlis, Takuya Masui, Sara Richardson, and Tadafumi Kato

Subjects
Paper, medicine.medical_specialty, Bipolar Disorder, Lithium (medication), medicine.drug_class, International Cooperation, Schizoaffective disorder, Antimanic Agents, 03 medical and health sciences, 0302 clinical medicine, ddc:150, medicine, Humans, Manic-depressive illness, Mood stabilizer, Antidepressants, Suicidal behavior, Genome-wide association study, Neurogenesis, Neuroplasticity, ddc:610, Bipolar disorder, Psychiatry, Biological Psychiatry, National Institute of Mental Health (U.S.), Genetics, medicine.disease, United States, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Mood, Phenotype, Pharmacogenetics, Lithium Compounds, Manic-depressive illness, Schizoaffective disorder, Mood stabilizer, Antidepressants, Suicidal behaviour, Genome-wide association study, Neurogenesis, Neuroplasticity, Antidepressant, Anxiety, medicine.symptom, Psychology, manisch-depressive Erkrankung, bipolare Störung, Schizoaffektive Störung, Stimmungsstabilisierer, Phasenprophylaktikum, Antidepressiva, Suizidalität, genomweite Assoziationsstudie, Neurogenese, Neuronale Plastizität, 030217 neurology & neurosurgery, Clinical psychology, medicine.drug
Abstract

For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic ‘fashions’, and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts. Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Published
2010

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