PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation
Abstract Genetic factors are relevant for both eating disorders and body weight regulation. A recent genome-wide association study (GWAS) for anorexia nervosa (AN) detected eight genome-wide significant chromosomal loci. One of these loci, rs10747478, was also genome-wide and significantly associate...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-06-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-02018-5 |
| _version_ | 1828335650460401664 |
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| author | Yiran Zheng Luisa Sophie Rajcsanyi Beate Herpertz-Dahlmann Jochen Seitz Martina de Zwaan Wolfgang Herzog Stefan Ehrlich Stephan Zipfel Katrin Giel Karin Egberts Roland Burghardt Manuel Föcker Saad Al-Lahham Triinu Peters Lars Libuda Jochen Antel Johannes Hebebrand Anke Hinney |
| author_facet | Yiran Zheng Luisa Sophie Rajcsanyi Beate Herpertz-Dahlmann Jochen Seitz Martina de Zwaan Wolfgang Herzog Stefan Ehrlich Stephan Zipfel Katrin Giel Karin Egberts Roland Burghardt Manuel Föcker Saad Al-Lahham Triinu Peters Lars Libuda Jochen Antel Johannes Hebebrand Anke Hinney |
| author_sort | Yiran Zheng |
| collection | DOAJ |
| description | Abstract Genetic factors are relevant for both eating disorders and body weight regulation. A recent genome-wide association study (GWAS) for anorexia nervosa (AN) detected eight genome-wide significant chromosomal loci. One of these loci, rs10747478, was also genome-wide and significantly associated with body mass index (BMI). The nearest coding gene is the Polypyrimidine Tract Binding Protein 2 gene (PTBP2). To detect mutations in PTBP2, Sanger sequencing of the coding region was performed in 192 female patients with AN (acute or recovered) and 191 children or adolescents with (extreme) obesity. Twenty-five variants were identified. Twenty-three of these were predicted to be pathogenic or functionally relevant in at least one in silico tool. Two novel synonymous variants (p.Ala77Ala and p.Asp195Asp), one intronic SNP (rs188987764), and the intronic deletion (rs561340981) located in the highly conserved region of PTBP2 may have functional consequences. Ten of 20 genes interacting with PTBP2 were studied for their impact on body weight regulation based on either previous functional studies or GWAS hits for body weight or BMI. In a GWAS for BMI (Pulit et al. 2018), the number of genome-wide significant associations at the PTBP2 locus was different between males (60 variants) and females (two variants, one of these also significant in males). More than 65% of these 61 variants showed differences in the effect size pertaining to BMI between sexes (absolute value of Z-score >2, two-sided p < 0.05). One LD block overlapping 5′UTR and all coding regions of PTBP2 comprises 56 significant variants in males. The analysis based on sex-stratified BMI GWAS summary statistics implies that PTBP2 may have a more pronounced effect on body weight regulation in males than in females. |
| first_indexed | 2024-04-13T21:50:21Z |
| format | Article |
| id | doaj.art-b0fc275d9ce7472994a1c28253750567 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-13T21:50:21Z |
| publishDate | 2022-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-b0fc275d9ce7472994a1c282537505672022-12-22T02:28:27ZengNature Publishing GroupTranslational Psychiatry2158-31882022-06-011211910.1038/s41398-022-02018-5PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulationYiran Zheng0Luisa Sophie Rajcsanyi1Beate Herpertz-Dahlmann2Jochen Seitz3Martina de Zwaan4Wolfgang Herzog5Stefan Ehrlich6Stephan Zipfel7Katrin Giel8Karin Egberts9Roland Burghardt10Manuel Föcker11Saad Al-Lahham12Triinu Peters13Lars Libuda14Jochen Antel15Johannes Hebebrand16Anke Hinney17Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-EssenDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-EssenDepartment of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of the RWTH AachenDepartment of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of the RWTH AachenDepartment of Psychosomatic Medicine and Psychotherapy, Hannover Medical SchoolDepartment of Internal Medicine II, General Internal and Psychosomatic Medicine, University of HeidelbergTranslational Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, TU-Dresden, University Hospital Carl Gustav Carus, Dresden University of TechnologyDepartment of Psychosomatic Medicine and Psychotherapy, Medical University HospitalDepartment of Psychosomatic Medicine and Psychotherapy, Medical University HospitalDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of WürzburgDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital FrankfurtDepartment of Child and Adolescent Psychiatry, University of MünsterDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National UniversityDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-EssenInstitute of Nutrition, Consumption and Health Faculty of Natural Sciences, University PaderbornDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-EssenDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-EssenDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-EssenAbstract Genetic factors are relevant for both eating disorders and body weight regulation. A recent genome-wide association study (GWAS) for anorexia nervosa (AN) detected eight genome-wide significant chromosomal loci. One of these loci, rs10747478, was also genome-wide and significantly associated with body mass index (BMI). The nearest coding gene is the Polypyrimidine Tract Binding Protein 2 gene (PTBP2). To detect mutations in PTBP2, Sanger sequencing of the coding region was performed in 192 female patients with AN (acute or recovered) and 191 children or adolescents with (extreme) obesity. Twenty-five variants were identified. Twenty-three of these were predicted to be pathogenic or functionally relevant in at least one in silico tool. Two novel synonymous variants (p.Ala77Ala and p.Asp195Asp), one intronic SNP (rs188987764), and the intronic deletion (rs561340981) located in the highly conserved region of PTBP2 may have functional consequences. Ten of 20 genes interacting with PTBP2 were studied for their impact on body weight regulation based on either previous functional studies or GWAS hits for body weight or BMI. In a GWAS for BMI (Pulit et al. 2018), the number of genome-wide significant associations at the PTBP2 locus was different between males (60 variants) and females (two variants, one of these also significant in males). More than 65% of these 61 variants showed differences in the effect size pertaining to BMI between sexes (absolute value of Z-score >2, two-sided p < 0.05). One LD block overlapping 5′UTR and all coding regions of PTBP2 comprises 56 significant variants in males. The analysis based on sex-stratified BMI GWAS summary statistics implies that PTBP2 may have a more pronounced effect on body weight regulation in males than in females.https://doi.org/10.1038/s41398-022-02018-5 |
| spellingShingle | Yiran Zheng Luisa Sophie Rajcsanyi Beate Herpertz-Dahlmann Jochen Seitz Martina de Zwaan Wolfgang Herzog Stefan Ehrlich Stephan Zipfel Katrin Giel Karin Egberts Roland Burghardt Manuel Föcker Saad Al-Lahham Triinu Peters Lars Libuda Jochen Antel Johannes Hebebrand Anke Hinney PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation Translational Psychiatry |
| title | PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation |
| title_full | PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation |
| title_fullStr | PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation |
| title_full_unstemmed | PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation |
| title_short | PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation |
| title_sort | ptbp2 a gene with relevance for both anorexia nervosa and body weight regulation |
| url | https://doi.org/10.1038/s41398-022-02018-5 |
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