Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

Manhattan Plot of All Genotyped and Imputed Single-Nucleotide Polymorphisms for 3,013 Tourette’s Syndrome-Obsessive-Compulsive Disorder European Ancestry Cases and 5,957 Controlsaa Red and blue lines indicate significance thresholds of 5×10−8 and 1×10−5, respectively.

Q-Q Plot of Nominal Disease Association p Values Versus Expected p Values Among the Cis eQTLs and mQTLs in Different Brain Tissues in the Tourette’s Syndrome, Obsessive-Compulsive Disorder (OCD), and Combined Genome-Wide Association Study (GWAS)aa eQTL=expression quantitative loci. A horizontal shift to the left from the diagonal line (of complete concordance between the observed p values and expected p values) in the Q-Q plot indicates enrichment.

Individual Disorder and Cross-Disorder Polygenic Score Analysis in Tourette’s Syndrome and Obsessive-Compulsive Disorder (OCD)aa The variance explained in two target samples (OCD European ancestry [EU] parent-child trios and Tourette’s French Canadian [FC] cases) is based on risk scores derived from an aggregated sum of weighted single-nucleotide polymorphism risk allele effect sizes estimated from discovery samples at six significance thresholds. The y axis indicates Nagelkerke’s pseudo R2. The p value under each discovery sample indicates how well the risk scores derived from the discovery sample can predict the illness phenotype in the target sample. N is the number of cases in each discovery sample. Negative R2 values indicate a negative correlation between risk scores and illness status in the target sample. OCD EU without known Tourette’s/chronic tics=European-ancestry OCD genome-wide association study (GWAS) samples after removing samples with known co-occurring Tourette’s/chronic tics; all OCD EU=European-ancestry OCD GWAS samples plus additional EU GWAS samples with co-occurring OCD and Tourette’s/chronic tics; combined Tourette’s/OCD EU=all European-ancestry Tourette’s GWAS samples and OCD GWAS samples; downsized OCD EU=randomly selected subset of OCD EU samples to match the number of cases in the Tourette’s EU discovery sample; Tourette’s EU=European-ancestry Tourette’s GWAS samples; OCD EU trios=the OCD EU parent-child trio probands and matched pseudo-control data derived from nontransmitted alleles; Tourette’s FC=Tourette’s French Canadian cases and matching controls. A permutation test was carried out to determine the significance of the difference in R2 between risk scores derived from OCD EU without known Tourette’s/chronic tics and all OCD EU, resulting in a two-sided empirical p value of 0.01. The inset box at upper right demonstrates the risk score elevations (difference in risk scores of transmitted alleles and untransmitted alleles in the OCD EU trios, standardized by the risk score of the untransmitted alleles) derived from three discovery samples: OCD EU without known Tourette’s/chronic tics, all OCD EU, and combined Tourette’s/OCD EU. Two-sided paired t tests were conducted for the pairwise comparisons of risk score elevations derived from three discovery samples.