S. Stewart - Academia.edu (original) (raw)

Papers by S. Stewart

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2007

Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnorma... more Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required. This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females. Family-based association candidate gene study. Participants were recruited from tertiary care OCD specialty clinics. OCD probands and their first degree relatives. Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes. Association between OCD and the three-marker haplotype rs12682807/ rs2072657/ rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P = 0.0015) and in males (global P = 0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P = 0.045). This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported.

PLOS ONE, 2015

Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a ... more 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.

by Cathy Budman, James McCracken, Michael Jenike, Danielle Posthuma, Damiaan Denys, Yves Dion, Luis Herrera, Peter Heutink, Guy Rouleau, Patrick Evans, S. Stewart, Jay Tischfield, Edwin Cook, Dongmei Yu, Eske Derks, Aline Sampaio, Ana Hounie, Maria Rosário, Yehuda Pollak, Fortu Benarroch, Jeremiah Scharf, Dan J Stein, Michele Pato, James Leckman, Humberto Nicolini, and Gholson Lyon

Journal of the American Academy of Child and Adolescent Psychiatry, 2014

Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental d... more Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). ...

by Cathy Budman, James McCracken, Michael Jenike, Daniel Geller, Danielle Posthuma, Jan Smit, Danielle Cath, Tobias Renner, Dieter Deforce, Damiaan Denys, Joseph Jankovic, Yves Dion, Ana Victoria Valencia Duarte, Peter Heutink, Guy Rouleau, Patrick Evans, S. Stewart, Jay Tischfield, Gerald Nestadt, Dongmei Yu, Edwin Cook, Eric Gamazon, Aline Sampaio, Ana Hounie, Yehuda Pollak, Jeremiah Scharf, Dan J Stein, Sian Hemmings, and James Leckman

PLoS genetics, 2013

The direct estimation of heritability from genome-wide common variant data as implemented in the ... more The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for ...

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2007

Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnorma... more Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required. This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females. Family-based association candidate gene study. Participants were recruited from tertiary care OCD specialty clinics. OCD probands and their first degree relatives. Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes. Association between OCD and the three-marker haplotype rs12682807/ rs2072657/ rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P = 0.0015) and in males (global P = 0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P = 0.045). This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported.

PLOS ONE, 2015

Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a ... more 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.

by Cathy Budman, James McCracken, Michael Jenike, Danielle Posthuma, Damiaan Denys, Yves Dion, Luis Herrera, Peter Heutink, Guy Rouleau, Patrick Evans, S. Stewart, Jay Tischfield, Edwin Cook, Dongmei Yu, Eske Derks, Aline Sampaio, Ana Hounie, Maria Rosário, Yehuda Pollak, Fortu Benarroch, Jeremiah Scharf, Dan J Stein, Michele Pato, James Leckman, Humberto Nicolini, and Gholson Lyon

Journal of the American Academy of Child and Adolescent Psychiatry, 2014

Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental d... more Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). ...

by Cathy Budman, James McCracken, Michael Jenike, Daniel Geller, Danielle Posthuma, Jan Smit, Danielle Cath, Tobias Renner, Dieter Deforce, Damiaan Denys, Joseph Jankovic, Yves Dion, Ana Victoria Valencia Duarte, Peter Heutink, Guy Rouleau, Patrick Evans, S. Stewart, Jay Tischfield, Gerald Nestadt, Dongmei Yu, Edwin Cook, Eric Gamazon, Aline Sampaio, Ana Hounie, Yehuda Pollak, Jeremiah Scharf, Dan J Stein, Sian Hemmings, and James Leckman

PLoS genetics, 2013

The direct estimation of heritability from genome-wide common variant data as implemented in the ... more The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for ...