Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

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=2 710(-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 Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone

Water Reservoirs in Small Planetary Bodies: Meteorites, Asteroids, and Comets

Asteroids and comets are the remnants of the swarm of planetesimals from which the planets ultimately formed, and they retain records of processes that operated prior to and during planet formation. They are also likely the sources of most of the water and other volatiles accreted by Earth. In this review, we discuss the nature and probable origins of asteroids and comets based on data from remote observations, in situ measurements by spacecraft, and laboratory analyses of meteorites derived from asteroids. The asteroidal parent bodies of meteorites formed ≤4 Ma after Solar System formation while there was still a gas disk present. It seems increasingly likely that the parent bodies of meteorites spectroscopically linked with the E-, S-, M- and V-type asteroids formed sunward of Jupiter's orbit, while those associated with C- and, possibly, D-type asteroids formed further out, beyond Jupiter but probably not beyond Saturn's orbit. Comets formed further from the Sun than any of the meteorite parent bodies, and retain much higher abundances of interstellar material. CI and CM group meteorites are probably related to the most common C-type asteroids, and based on isotopic evidence they, rather than comets, are the most likely sources of the H and N accreted by the terrestrial planets. However, comets may have been major sources of the noble gases accreted by Earth and Venus. Possible constraints that these observations can place on models of giant planet formation and migration are explored