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.

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1,465 cases, 5,557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9,657 X-chromosome SNPs. Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two p-values were located within DLGAP1 (p=2.49×10-6 and p=3.44×10-6), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a p-value=3.84 × 10-8. However, when trios were meta-analyzed with the combined case-control samples, the p-value for this variant was 3.62×10-5, losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation-QTLs (p<0.001) and frontal lobe eQTLs (p=0.001) was observed within the top-ranked SNPs (p<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

IntroductionBody Integrity Identity Disorder (BIID) is a rare, infrequently studied and highly secretive condition in which there is a mismatch between the mental body image and the physical body. Subjects suffering from BIID have an intense desire to amputate a major limb or severe the spinal cord in order to become paralyzed. Aim of the study is to broaden the knowledge of BIID amongst medical professionals, by describing all who deal with BIID.MethodsSomatic, psychiatric and BIID characteristic data were collected from 54 BIID individuals using a detailed questionnaire. Subsequently, data of different subtypes of BIID (i.e. wish for amputation or paralyzation) were evaluated. Finally, disruption in work, social and family life due to BIID in subjects with and without amputation were compared.ResultsBased on the subjects' reports we found that BIID has an onset in early childhood. The main rationale given for their desire for body modification is to feel complete or to feel satisfied inside. Somatic and severe psychiatric co-morbidity is unusual, but depressive symptoms and mood disorders can be present, possibly secondary to the enormous distress BIID puts upon a person. Amputation and paralyzation variant do not differ in any clinical variable. Surgery is found helpful in all subjects who underwent amputation and those subjects score significantly lower on a disability scale than BIID subjects without body modification.ConclusionsThe amputation variant and paralyzation variant of BIID are to be considered as one of the same condition. Amputation of the healthy body part appears to result in remission of BIID and an impressive improvement of quality of life. Knowledge of and respect for the desires of BIID individuals are the first steps in providing care and may decrease the huge burden they experience.

Our body feels like it is ours. However, individuals with body integrity identity disorder (BIID) lack this feeling of ownership for distinct limbs and desire amputation of perfectly healthy body parts. This extremely rare condition provides us with an opportunity to study the neural basis underlying the feeling of limb ownership, since these individuals have a feeling of disownership for a limb in the absence of apparent brain damage. Here we directly compared brain activation between limbs that do and do not feel as part of the body using functional MRI during separate tactile stimulation and motor execution experiments. In comparison to matched controls, individuals with BIID showed heightened responsivity of a large somatosensory network including the parietal cortex and right insula during tactile stimulation, regardless of whether the stimulated leg felt owned or alienated. Importantly, activity in the ventral premotor cortex depended on the feeling of ownership and was reduced during stimulation of the alienated compared to the owned leg. In contrast, no significant differences between groups were observed during the performance of motor actions. These results suggest that altered somatosensory processing in the premotor cortex is associated with the feeling of disownership in BIID, which may be related to altered integration of somatosensory and proprioceptive information.