4.4 Article

Case-control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population

期刊

JOURNAL OF HUMAN GENETICS
卷 54, 期 2, 页码 98-107

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/jhg.2008.14

关键词

Bulgarian population; case-control study; DRD2; schizophrenia; SNP

向作者/读者索取更多资源

The development of molecular psychiatry in the last few decades identified a number of candidate genes that could be associated with schizophrenia. A great number of studies often result with controversial and non-conclusive outputs. However, it was determined that each of the implicated candidates would independently have a minor effect on the susceptibility to that disease. Herein we report results from our replication study for association using 255 Bulgarian patients with schizophrenia and schizoaffective disorder and 556 Bulgarian healthy controls. We have selected from the literatures 202 single nucleotide polymorphisms (SNPs) in 59 candidate genes, which previously were implicated in disease susceptibility, and we have genotyped them. Of the 183 SNPs successfully genotyped, only 1 SNP, rs6277 (C957T) in the DRD2 gene (P=0.0010, odds ratio=1.76), was considered to be significantly associated with schizophrenia after the replication study using independent sample sets. Our findings support one of the most widely considered hypotheses for schizophrenia etiology, the dopaminergic hypothesis.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Psychology, Clinical

The dynamic interplay between sleep and mood: an intensive longitudinal study of individuals with bipolar disorder

K. J. S. Lewis, K. Tilling, K. Gordon-Smith, K. E. A. Saunders, A. Di Florio, L. Jones, I Jones, M. C. O'Donovan, J. Heron

Summary: This study examined the longitudinal relationships between sleep and mood in individuals with bipolar disorder. The results showed bidirectional relationships between insomnia and depressive symptoms, but weak support for bidirectional relationships between insomnia and (hypo)manic symptoms. The strength of these associations varied depending on age, gender, bipolar subtype, and history of rapid cycling.

PSYCHOLOGICAL MEDICINE (2023)

Letter Genetics & Heredity

Spinal muscular atrophy with congenital bone fractures 2 caused by a rare loss-of-function ASCC1 gene mutation in two Bulgarian Roma patients

Irena Bradinova, Silvia Andonova, Radoslava Vazharova, Stiliyana Tomova, Lubomir Balabanski, Alexey Savov

CLINICAL GENETICS (2022)

Article Multidisciplinary Sciences

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Vassily Trubetskoy, Antonio F. Pardinas, Ting Qi, Georgia Panagiotaropoulou, Swapnil Awasthi, Tim B. Bigdeli, Julien Bryois, Chia-Yen Chen, Charlotte A. Dennison, Lynsey S. Hall, Max Lam, Kyoko Watanabe, Oleksandr Frei, Tian Ge, Janet C. Harwood, Frank Koopmans, Sigurdur Magnusson, Alexander L. Richards, Julia Sidorenko, Yang Wu, Jian Zeng, Jakob Grove, Minsoo Kim, Zhiqiang Li, Georgios Voloudakis, Wen Zhang, Mark Adams, Ingrid Agartz, Elizabeth G. Atkinson, Esben Agerbo, Mariam Al Eissa, Margot Albus, Madeline Alexander, Behrooz Z. Alizadeh, Koksal Alptekin, Thomas D. Als, Farooq Amin, Volker Arolt, Manuel Arrojo, Lavinia Athanasiu, Maria Helena Azevedo, Silviu A. Bacanu, Nicholas J. Bass, Martin Begemann, Richard A. Belliveau, Judit Bene, Beben Benyamin, Sarah E. Bergen, Giuseppe Blasi, Julio Bobes, Stefano Bonassi, Alice Braun, Rodrigo Affonseca Bressan, Evelyn J. Bromet, Richard Bruggeman, Peter F. Buckley, Randy L. Buckner, Jonas Bybjerg-Grauholm, Wiepke Cahn, Murray J. Cairns, Monica E. Calkins, Vaughan J. Carr, David Castle, Stanley Catts, Kimberley D. Chambert, Raymond C. K. Chan, Boris Chaumette, Wei Cheng, Eric F. C. Cheung, Siow Ann Chong, David Cohen, Angele Consoli, Quirino Cordeiro, Javier Costas, Charles Curtis, Michael Davidson, Kenneth L. Davis, Lieuwe de Haan, Franziska Degenhardt, Lynn E. DeLisi, Ditte Demontis, Faith Dickerson, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Jubao Duan, Giuseppe Ducci, Frank Dudbridge, Johan G. Eriksson, Lourdes Fananas, Stephen Faraone, Alessia Fiorentino, Andreas Forstner, Josef Frank, Nelson B. Freimer, Menachem Fromer, Alessandra Frustaci, Ary Gadelha, Giulio Genovese, Elliot S. Gershon, Marianna Giannitelli, Ina Giegling, Paola Giusti-Rodriguez, Stephanie Godard, Jacqueline Goldstein, Javier Gonzalez Penas, Ana Gonzalez-Pinto, Srihari Gopal, Jacob Gratten, Michael F. Green, Tiffany A. Greenwood, Olivier Guillin, Sinan Guloksuz, Raquel E. Gur, Ruben C. Gur, Blanca Gutierrez, Eric Hahn, Hakon Hakonarson, Vahram Haroutunian, Annette M. Hartmann, Carol Harvey, Caroline Hayward, Frans A. Henskens, Stefan Herms, Per Hoffmann, Daniel P. Howrigan, Masashi Ikeda, Conrad Iyegbe, Inge Joa, Antonio Julia, Anna K. Kahler, Tony Kam-Thong, Yoichiro Kamatani, Sena Karachanak-Yankova, Oussama Kebir, Matthew C. Keller, Brian J. Kelly, Andrey Khrunin, Sung-Wan Kim, Janis Klovins, Nikolay Kondratiev, Bettina Konte, Julia Kraft, Michiaki Kubo, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Agung Kusumawardhani, Hana Kuzelov A-Ptackova, Stefano Landi, Laura C. Lazzeroni, Phil H. Lee, Sophie E. Legge, Douglas S. Lehrer, Rebecca Lencer, Bernard Lerer, Miaoxin Li, Jeffrey Lieberman, Gregory A. Light, Svetlana Limborska, Chih-Min Liu, Jouko Lonnqvist, Carmel M. Loughland, Jan Lubinski, Jurjen J. Luykx, Amy Lynham, Milan Macek, Andrew Mackinnon, Patrik K. E. Magnusson, Brion S. Maher, Wolfgang Maier, Dolores Malaspina, Jacques Mallet, Stephen R. Marder, Sara Marsal, Alicia R. Martin, Lourdes Martorell, Manuel Mattheisen, Robert W. McCarley, Colm McDonald, John J. McGrath, Helena Medeiros, Sandra Meier, Bela Melegh, Ingrid Melle, Raquelle Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Marina Mitjans, Espen Molden, Esther Molina, Maria Dolores Molto, Valeria Mondelli, Carmen Moreno, Christopher P. Morley, Gerard Muntane, Kieran C. Murphy, Inez Myin-Germeys, Igor Nenadic, Gerald Nestadt, Liene Nikitina-Zake, Cristiano Noto, Keith H. Nuechterlein, Niamh Louise O'Brien, F. Anthony O'Neill, Sang-Yun Oh, Ann Olincy, Vanessa Kiyomi Ota, Christos Pantelis, George N. Papadimitriou, Mara Parellada, Tiina Paunio, Renata Pellegrino, Sathish Periyasamy, Diana O. Perkins, Bruno Pfuhlmann, Olli Pietilainen, Jonathan Pimm, David Porteous, John Powell, Diego Quattrone, Digby Quested, Allen D. Radant, Antonio Rampino, Mark H. Rapaport, Anna Rautanen, Abraham Reichenberg, Cheryl Roe, Joshua L. Roffman, Julian Roth, Matthias Rothermundt, Bart P. F. Rutten, Safaa Saker-Delye, Veikko Salomaa, Julio Sanjuan, Marcos Leite Santoro, Adam Savitz, Ulrich Schall, Rodney J. Scott, Larry J. Seidman, Sally Isabel Sharp, Jianxin Shi, Larry J. Siever, Engilbert Sigurdsson, Kang Sim, Nora Skarabis, Petr Slominsky, Hon-Cheong So, Janet L. Sobell, Erik Soderman, Helen J. Stain, Nils Eiel Steen, Agnes A. Steixner-Kumar, Elisabeth Stogmann, William S. Stone, Richard E. Straub, Fabian Streit, Eric Strengman, T. Scott Stroup, Mythily Subramaniam, Catherine A. Sugar, Jaana Suvisaari, Dragan M. Svrakic, Neal R. Swerdlow, Jin P. Szatkiewicz, Thi Minh Tam Ta, Atsushi Takahashi, Chikashi Terao, Florence Thibaut, Draga Toncheva, Paul A. Tooney, Silvia Torretta, Sarah Tosato, Gian Battista Tura, Bruce Turetsky, Alp Ucok, Arne Vaaler, Therese van Amelsvoort, Ruud van Winkel, Juha Veijola, John Waddington, Henrik Walter, Anna Waterreus, Bradley T. Webb, Mark Weiser, Nigel M. Williams, Stephanie H. Witt, Brandon K. Wormley, Jing Qin Wu, Zhida Xu, Robert Yolken, Clement C. Zai, Wei Zhou, Feng Zhu, Fritz Zimprich, Muhammad Ayub, Christian Benner, Alessandro Bertolino, Donald W. Black, Nicholas J. Bray, Gerome Breen, Nancy G. Buccola, William F. Byerley, Wei J. Chen, C. Robert Cloninger, Benedicto Crespo-Facorro, Gary Donohoe, Robert Freedman, Cherrie Galletly, Michael J. Gandal, Massimo Gennarelli, David M. Hougaard, Hai-Gwo Hwu, Assen Jablensky, Steven A. McCarroll, Jennifer L. Moran, Ole Mors, Preben B. Mortensen, Bertram Muller-Myhsok, Amanda L. Neil, Merete Nordentoft, Michele T. Pato, Tracey L. Petryshen, Matti Pirinen, Ann E. Pulver, Thomas G. Schulze, Jeremy M. Silverman, Jordan W. Smoller, Eli A. Stahl, Debby W. Tsuang, Elisabet Vilella, Shi-Heng Wang, Shuhua Xu, Rolf Adolfsson, Celso Arango, Bernhard T. Baune, Sintia Iole Belangero, Anders D. Borglum, David Braff, Elvira Bramon, Joseph D. Buxbaum, Dominique Campion, Jorge A. Cervilla, Sven Cichon, David A. Collier, Aiden Corvin, David Curtis, Marta Di Forti, Enrico Domenici, Hannelore Ehrenreich, Valentina Escott-Price, Tonu Esko, Ayman H. Fanous, Anna Gareeva, Micha Gawlik, Pablo Gejman, Michael Gill, Stephen J. Glatt, Vera Golimbet, Kyung Sue Hong, Christina M. Hultman, Steven E. Hyman, Nakao Iwata, Erik G. Jonsson, Rene S. Kahn, James L. Kennedy, Elza Khusnutdinova, George Kirov, James A. Knowles, Marie-Odile Krebs, Claudine Laurent-Levinson, Jimmy Lee, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Dheeraj Malhotra, Andrew McIntosh, Andrew McQuillin, Paulo R. Menezes, Vera A. Morgan, Derek W. Morris, Bryan J. Mowry, Robin M. Murray, Vishwajit Nimgaonkar, Markus M. Nothen, Roel A. Ophoff, Sara A. Paciga, Aarno Palotie, Carlos N. Pato, Shengying Qin, Marcella Rietschel, Brien P. Riley, Margarita Rivera, Dan Rujescu, Meram C. Saka, Alan R. Sanders, Sibylle G. Schwab, Alessandro Serretti, Pak C. Sham, Yongyong Shi, David St Clair, Hreinn Stefansson, Kari Stefansson, Ming T. Tsuang, Jim van Os, Marquis P. Vawter, Daniel R. Weinberger, Thomas Werge, Dieter B. Wildenauer, Xin Yu, Weihua Yue, Peter A. Holmans, Andrew J. Pocklington, Panos Roussos, Evangelos Vassos, Matthijs Verhage, Peter M. Visscher, Jian Yang, Danielle Posthuma, Ole A. Andreassen, Kenneth S. Kendler, Michael J. Owen, Naomi R. Wray, Mark J. Daly, Hailiang Huang, Benjamin M. Neale, Patrick F. Sullivan, Stephan Ripke, James T. R. Walters, Michael C. O'Donovan

Summary: In this study, a two-stage genome-wide association study was conducted to identify common variants associated with schizophrenia. The results revealed 287 distinct genomic loci and 120 genes likely to be involved in the development of schizophrenia. This research provides valuable insights into the pathophysiology of schizophrenia and offers a resource for further mechanistic studies.

NATURE (2022)

Article Biotechnology & Applied Microbiology

Detection of pathogenic variants in Alzheimer's disease related genes in Bulgarian patients by pooled whole-exome sequencing

Sena Karachanak-Yankova, Dimitar Serbezov, Marta Mihaylova, Dragomira Nikolova, Lubomir Balabanski, Vera Damyanova, Olga Antonova, Rada Staneva, Mihail Ganev, Victoria Spasova, Blaga Rukova, Desislava Nesheva, Slavica Josifovska, Mikaela Stancheva, Diana Belejanska, Mariya Petrova, Shima Mehrabian, Latchezar Traykov, Savina Hadjidekova, Draga Toncheva

Summary: To understand the genetic background of Alzheimer's disease (AD), we sequenced the exome of 66 Bulgarian AD patients and analyzed genes known to be associated with AD. We identified six pathogenic/likely pathogenic variants, including variants in genes such as PSEN1, PSEN2, APP, APOE, TREM2, HFE, CLU, and CR1. Among these variants, two showed no significant difference between AD patients and controls, while three were significantly associated with AD. This study highlights the role of these variants in the complex genetic etiology of AD.

BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT (2023)

Article Biochemistry & Molecular Biology

Golgi apparatus, endoplasmic reticulum and mitochondrial function implicated in Alzheimer's disease through polygenic risk and RNA sequencing

Karen Crawford, Ganna Leonenko, Emily Baker, Detelina Grozeva, Benoit Lan-Leung, Peter Holmans, Julie Williams, Michael C. O'Donovan, Valentina Escott-Price, Dobril K. Ivanov

Summary: Polygenic risk scores (PRS) are widely used to measure common variant liability and predict the risk of Alzheimer's disease (AD) development. This study analyzed the differential gene expression and disrupted biological pathways in AD cases, controls, and PRS using human brain-derived samples. The results revealed already implicated mechanisms and identified new processes. Glia and microglia-related terms were significantly disrupted. The findings suggest that PRS stratification can be used when suitable case/control samples are not available or in clinical trials.

MOLECULAR PSYCHIATRY (2023)

Article Genetics & Heredity

A mutational hotspot in AMOTL1 defines a new syndrome of orofacial clefting, cardiac anomalies, and tall stature

Alanna Strong, Soumya Rao, Sandra von Hardenberg, Dong Li, Liza L. Cox, Paul C. Lee, Li Q. Zhang, Waheed Awotoye, Tamir Diamond, Jessica Gold, Catherine Gooch, Lord Jephthah Joojo Gowans, Hakon Hakonarson, Anne Hing, Kathleen Loomes, Nicole Martin, Mary L. Marazita, Tarja Mononen, David Piccoli, Rolph Pfundt, Salmo Raskin, Stephen W. Scherer, Nara Sobriera, Courtney Vaccaro, Xiang Wang, Deborah Watson, Rosanna Weksberg, Elizabeth Bhoj, Jeffrey C. Murray, Andrew C. Lidral, Azeez Butali, Michael F. Buckley, Tony Roscioli, David A. Koolen, Laurie H. Seaver, Cynthia A. Prows, Rolf W. Stottmann, Timothy C. Cox

Summary: AMOTL1 encodes angiomotin-like protein 1, a protein that regulates cell polarity, adhesion, and migration. Variants in AMOTL1 are associated with orofacial clefting, congenital heart disease, tall stature, auricular anomalies, and gastrointestinal manifestations. The study suggests that missense variants in AMOTL1, particularly in the region affecting amino acids 157-161, define a new orofacial clefting syndrome and highlight the importance of this region in its function.

AMERICAN JOURNAL OF MEDICAL GENETICS PART A (2023)

Editorial Material Biochemistry & Molecular Biology

Dopa-responsive dystonia in Bulgarian patients: report of three cases

Maya Atanasoska, Radoslava Vazharova, Galina Stevanovic, Irena Bradinova, Slavyana Yaneva Staykova, Lubomir Balabanski, Daniela Mircheva, Daniela Avdjieva-Tzavella, Draga Toncheva

Summary: This study reports three cases of Dopa-responsive dystonia (DRD), including two cases of TH deficiency with compound heterozygous missense variants in the TH gene, and one case of GCH1 deficiency with a heterozygous pathogenic variant in the GCH1 gene. The diagnosis of DRD was determined by whole exome sequencing and whole genome sequencing. The aim of this study is to increase awareness for DRD, especially in Bulgaria, as early diagnosis is crucial for prognosis and therapy outcome.

EUROPEAN JOURNAL OF HUMAN GENETICS (2023)

Article Biochemistry & Molecular Biology

Family-based analysis of the contribution of rare and common genetic variants to school performance in schizophrenia

Alexandros Rammos, George Kirov, Leon Hubbard, James T. R. Walters, Peter Holmans, Michael J. Owen, Michael C. O'Donovan, Elliott Rees

Summary: Impaired cognition in schizophrenia is associated with worse functional outcomes. Genetic factors, including both common and rare variants, contribute to school performance in schizophrenia. Damaging de novo coding variants in genes associated with developmental disorders have significant effects on school performance, and are also linked to comorbid mild intellectual disability. Non-transmitted parental common alleles do not have significant effects on school performance in schizophrenia.

MOLECULAR PSYCHIATRY (2023)

Review Biochemistry & Molecular Biology

Genomic findings in schizophrenia and their implications

Michael J. Owen, Sophie E. Legge, Elliott Rees, James T. R. Walters, Michael C. O'Donovan

Summary: There has been significant progress in understanding the genetics of schizophrenia in the past 15 years. The condition has been found to be highly polygenic, with the majority of heritability coming from common alleles of small effect. Additionally, rare copy number and coding variants also contribute to the genetic basis of the disorder. Specific genes and loci have been identified, indicating disturbances in neuronal and synaptic functions. The genetic findings have also revealed the close relationship between schizophrenia and bipolar disorder and childhood neurodevelopmental disorders, and provided an explanation for the persistence of common risk alleles in the population despite reduced fertility.

MOLECULAR PSYCHIATRY (2023)

Article Biochemistry & Molecular Biology

Estimating the impact of transmitted and non-transmitted psychiatric and neurodevelopmental polygenic scores on youth emotional problems

Amy Shakeshaft, Joanna Martin, Charlotte A. Dennison, Lucy Riglin, Cathryn M. Lewis, Michael C. O'Donovan, Anita Thapar

Summary: This study examined the contribution of parental non-transmitted genetic liability to youth emotional problems. The results showed that genetic liability for anxiety, depression, ADHD, and ASD were associated with youth emotional problems, with stronger associations in adolescence. However, there was limited evidence for non-transmitted genetic effects.

MOLECULAR PSYCHIATRY (2023)

Meeting Abstract Biochemistry & Molecular Biology

Whole-exome sequencing indicates enrichment in MAP kinase activation pathway genes in Bulgarian dementia patients

Marta Mihaylova, Dimitar Serbezov, Lubomir Balabanski, Sena Karachanak-Yankova, Dragomira Nikolova, Mihail Ganev, Vera Damyanova, Desislava Nesheva, Zora Hammoudeh, Blaga Rukova, Diyana Belezhanska, Shima Mehrabian, Maria Petrova, Latchezar Traykov, Savina Hadjidekova, Draga Toncheva

EUROPEAN JOURNAL OF HUMAN GENETICS (2022)

Meeting Abstract Biochemistry & Molecular Biology

Genomic data suggests the involvement of TLR5 variants in modifyingthe risk for Alzheimer's disease

Dragomira N. Nikolova, Dimitar Serbezov, Mihail Ganev, Sena Karachanak-Yankova, Marta Mihaylova, Shima Mehrabian, Maria Petrova, Vera Damyanova, Diyana Belezhanska, Lachezar Traykov, Savina Hadjidekova, Draga Toncheva

EUROPEAN JOURNAL OF HUMAN GENETICS (2022)

Meeting Abstract Biochemistry & Molecular Biology

Whole-exome sequencing reveals differential enhancement of ion channels activity genes between Alzheimer patients and controls

Dimitar Serbezov, Maja Atanasoska, Lubomir Balabanski, Sena Karachanak-Yankova, Radoslava Vazharova, Dragomira Nikolova, Marta Mihaylova, Rada Staneva, Olga Antonova, Vera Damyanova, Mihail Ganev, Viktoria Spasova, Dessislava Nesheva, Zora Hammoudeh, Savina Hadjidekova, Diyana Belezhanska, Shima Mehrabian, Maria Petrova, Latchezar Traykov, Draga Toncjeva

EUROPEAN JOURNAL OF HUMAN GENETICS (2022)

Meeting Abstract Biochemistry & Molecular Biology

Identifying lipid metabolism genes with a potential role in the pathogenesis of Frontotemporal dementia through pool exome sequencing

Mihail Ganev, Dimitar Serbezov, Lubomir Balabanski, Radoslava Vazharova, Sena Karachanak-Yankova, Olga Antonova, Dragomira Nikolova, Marta Mihaylova, Rada Staneva, Viktoria Spasova, Vera Damyanova, Desislava Nesheva, Zora Hammoudeh, Blaga Rukova, Savina Hadjidekova, Shima Mehrabian, Maria Petrova, Diana Belezhanska, Lachezar Traykov, Draga Toncheva

EUROPEAN JOURNAL OF HUMAN GENETICS (2022)

Meeting Abstract Biochemistry & Molecular Biology

Analysis of pathogenic variants in Alzheimer's disease related genes in cases, healthy young controls and centenarians

Sena Karachanak-Yankova, Dimitar Serbezov, Lubomir Balabanski, Marta Mihaylova, Dragomira Nikolova, Mihail Ganev, Desislava Nesheva, Zora Hammoudeh, Blaga Rukova, T. Dekova, Diyana Belezhanska, Shima Mehrabian, Mariya Petrova, Latchezar Traykov, Savina Hadjidekova, Draga Toncheva

EUROPEAN JOURNAL OF HUMAN GENETICS (2022)

暂无数据