ALINE SANTOS SAMPAIO
Projetos de Pesquisa
Unidades Organizacionais
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
2 resultados
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- COMT and MAO-A Polymorphisms and Obsessive-Compulsive Disorder: A Family-Based Association Study(2015) SAMPAIO, Aline Santos; HOUNIE, Ana Gabriela; PETRIBU, Katia; CAPPI, Carolina; MORAIS, Ivanil; VALLADA, Homero; ROSARIO, Maria Conceicao do; STEWART, S. Evelyn; FARGENESS, Jesen; MATHEWS, Carol; ARNOLD, Paul; HANNA, Gregory L.; RICHTER, Margaret; KENNEDY, James; FONTENELLE, Leonardo; PEREIRA, Carlos Alberto de Braganca; PAULS, David L.; MIGUEL, Euripedes ConstantinoObjective Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design. Methods Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed. Results OCD, broad and narrow phenotypes, were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A. Conclusions The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.
- Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD(2015) YU, Dongmei; MATHEWS, Carol A.; SCHARF, Jeremiah M.; NEALE, Benjamin M.; DAVIS, Lea K.; GAMAZON, Eric R.; DERKS, Eske M.; EVANS, Patrick; EDLUND, Christopher K.; CRANE, Jacquelyn; OSIECKI, Lisa; RENNER, Tobias; REUS, Victor I.; RICHTER, Margaret A.; RIDDLE, Mark A.; ROBERTSON, Mary M.; ROMERO, Roxana; ROSARIO, Maria C.; ROSENBERG, David; RUHRMANN, Stephan; SABATTI, Chiara; GALLAGHER, Patience; SALVI, Erika; SAMPAIO, Aline S.; SAMUELS, Jack; SANDOR, Paul; SERVICE, Susan K.; SHEPPARD, Brooke; SINGER, Harvey S.; SMIT, Jan H.; STEIN, Dan J.; STRENGMAN, Eric; GERBER, Gloria; TISCHFIELD, Jay A.; TURIEL, Maurizio; DUARTE, Ana V. Valencia; VALLADA, Homero; VEENSTRA-VANDERWEELE, Jeremy; WALITZA, Susanne; WANG, Ying; WEALE, Mike; WEISS, Robert; WENDLAND, Jens R.; HADDAD, Stephen; WESTENBERG, Herman G. M.; SHUGART, Yin Yao; HOUNIE, Ana G.; MIGUEL, Euripedes C.; NICOLINI, Humberto; WAGNER, Michael; RUIZ-LINARES, Andres; CATH, Danielle C.; MCMAHON, William; POSTHUMA, Danielle; ILLMANN, Cornelia; OOSTRA, Ben A.; NESTADT, Gerald; ROUTEAU, Guy A.; PURCELL, Shaun; JENIKE, Michael A.; HEUTINK, Peter; HANNA, Gregory L.; CONTI, David V.; ARNOLD, Paul D.; FREIMER, Nelson B.; MCGRATH, Lauren M.; STEWART, Evelyn; KNOWLES, James A.; COX, Nancy J.; PAULS, David L.; MAYERFELD, Catherine; AREPALLI, Sampath; BARLASSINA, Cristina; BARR, Cathy L.; BELLODI, Laura; BENARROCH, Fortu; BERRIO, Gabriel Bedoya; BIENVENU, O. Joseph; BLACK, Donald W.; BLOCH, Michael H.; BRENTANI, Helena; BRUUN, Ruth D.; BUDMAN, Cathy L.; CAMARENA, Beatriz; CAMPBELL, Desmond D.; CAPPI, Carolina; SILGADO, Julio C. Cardona; CAVALLINI, Maria C.; CHAVIRA, Denise A.; CHOUINARD, Sylvain; COOK, Edwin H.; COOKSON, M. R.; CORIC, Vladimir; CULLEN, Bernadette; CUSI, Daniete; DELORME, Richard; DENYS, Damiaan; DION, Yves; EAPEN, Valsama; EGBERTS, Karin; FALKAI, Peter; FERNANDEZ, Thomas; FOURNIER, Eduardo; GARRIDO, Helena; GELLER, Daniel; GILBERT, Donald L.; GIRARD, Simon L.; GRABE, Hans J.; GRADOS, Marco A.; GREENBERG, Benjamin D.; GROSS-TSUR, Varda; GRUENBLATT, Edna; HARDY, John; HEIMAN, Gary A.; HEMMINGS, Sian M. J.; HERRERA, Luis D.; HEZEL, Dianne M.; HOEKSTRA, Pieter J.; JANKOVIC, Joseph; KENNEDY, James L.; KING, Robert A.; KONKASHBAEV, Anuar I.; KREMEYER, Barbara; KURLAN, Roger; LANZAGORTA, Nuria; LEBOYER, Marion; LECKMAN, James F.; LENNERTZ, Leonhard; LIU, Chunyu; LOCHNER, Christine; LOWE, Thomas L.; LUPOLI, Sara; MACCIARDI, Fabio; MAIER, Wolfgang; MANUNTA, Paolo; MARCONI, Maurizio; MCCRACKEN, James T.; RESTREPO, Sandra C. Mesa; MOESSNER, Rainald; MOORJANI, Priya; MORGAN, Jubel; MULLER, Heike; MURPHY, Dennis L.; NAARDEN, Allan L.; NURMI, Erika; OCHOA, William Cornejo; OPHOFF, Roel A.; PAKSTIS, Andrew J.; PATO, Michele T.; PATO, Carlo N.; PIACENTINI, John; PITTENGER, Christopher; POLLAK, Yehuda; RAUCH, Scott L.Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. Method: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders Polygenic score analyses identified a significant polygenic component for OCD (p=2x10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01). Conclusions: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring burette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.