Evidence for a heritable unidimensional symptom factor underlying obsessionality

Mathews, Carol A.; Greenwood, Tiffany A.; Wessel, Jennifer; Azzam, Amin; Garrido, Helena; Chavira, Denise A.; Chandavarkar, Uma; Bagnarello, Monica; Stein, Murray B.; Schork, Nicholas J.

doi:10.1002/ajmg.b.30660

Cited by 14 publications

(15 citation statements)

References 71 publications

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“…Interestingly, the contamination and hoarding/symmetry factor showed significant genetic correlations as well, as did the taboo and doubts factor. This latter correlation corroborates previous work in college students and clinical samples strongly suggesting a heritable obsessionality factor strongly related to OCD (Mathews et al 2008). …”

Section: Discussionsupporting

confidence: 91%

Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates

et al. 2010

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To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.

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Section: Discussionsupporting

confidence: 91%

Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates

et al. 2010

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“…This study represents the first effort to use genome-wide genotype data to determine the heritability of two related neuropsychiatric disorders, OCD and TS. The narrow-sense heritability of each disorder (h 2 GCTA = 0.58 for TS and 0.37 for OCD) correspond well with previously reported heritability estimates from family and twin studies [17], [19], [20], [21], [22], [23]–[25], [26], [27], [28], [29], [49] suggesting that there is little, if any, heritability “missing” (i.e., unassayed). While previous TS and OCD GWAS have been underpowered to identify individual susceptibility variants with modest effect sizes, based on these results, future GWAS in much larger samples should identify a large number of true TS and OCD disease variants.…”

Section: Discussionsupporting

confidence: 85%

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

et al. 2013

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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 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

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“…In addition some studies provide evidence for a common heritable OCS phenotype underlying several OCS dimensions (Clifford et al 1984;Mathews et al 2007; van Grootheest et al 2008b). Van Grootheest et al (2008b) in a multivariate twin analysis in adult female twins (N=1383) demonstrated acceptable fit for the common pathway model, in which a latent OC behavior phenotype was modeled to underlie and predict three OCS dimensions of Rumination, Contamination and Checking (identified by exploratory factor analysis of the 20-item Padua Inventory).…”

Section: Discussionmentioning

confidence: 94%

“…In these settings OCS has usually been measured by means of various OCD screening questionnaires, the most commonly used being the 20-item survey form of the Leyton Obsessional Inventory-Children's Version (20-item LOI-CV) . Unlike other OCD screening tools, which in order to facilitate use consist of few items and are as a result unidimensional in nature (Hudziak et al 2006;Uher et al 2007), there is evidence to suggest that the factor structure of the 20-item LOI-CV is multidimensional (Bamber et al 2002;Berg et al 1988;Maggini et al 2001;Mathews et al 2007). Studies are inconsistent, however, in the number and nature of factors identified.…”

Section: Introductionmentioning

confidence: 90%

Alternative Factor Models and Heritability of the Short Leyton Obsessional Inventory—Children’s Version

Moore

Smith

Shevlin

et al. 2010

J Abnorm Child Psychol

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An alternative models framework was used to test three confirmatory factor analytic models for the Short Leyton Obsessional Inventory-Children's Version (Short LOI-CV) in a general population sample of 517 young adolescent twins (11-16 years). A one-factor model as implicit in current classification systems of Obsessive-Compulsive Disorder (OCD), a two-factor obsessions and compulsions model, and a multidimensional model corresponding to the three proposed subscales of the Short LOI-CV (labelled Obsessions/Incompleteness, Numbers/Luck and Cleanliness) were considered. The three-factor model was the only model to provide an adequate explanation of the data. Twin analyses suggested significant quantitative sex differences in heritability for both the Obsessions/Incompleteness and Numbers/Luck dimensions with these being significantly heritable in males only (heritability of 60% and 65% respectively). The correlation between the additive genetic effects for these two dimensions in males was 0.95 suggesting they largely share the same genetic risk factors.

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Evidence for a heritable unidimensional symptom factor underlying obsessionality

Cited by 14 publications

References 71 publications

Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates

Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Alternative Factor Models and Heritability of the Short Leyton Obsessional Inventory—Children’s Version

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