Highlights d Three groups of highly genetically-related disorders among 8 psychiatric disorders d Identified 109 pleiotropic loci affecting more than one disorder d Pleiotropic genes show heightened expression beginning in 2 nd prenatal trimester d Pleiotropic genes play prominent roles in neurodevelopmental processes Authors Cross-Disorder Group of the Psychiatric Genomics Consortium

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

Obsessive-compulsive disorder is a familial disorder. Obsessions are more specific to the phenotype than are compulsions. Age at onset of OCD is valuable in characterizing a familial subtype.

Little is known about the prevalence and correlates of hoarding behavior in the community. We estimated the prevalence and evaluated correlates of hoarding in 742 participants in the Hopkins Epidemiology of Personality Disorder Study. The prevalence of hoarding was nearly 4% (5.3%, weighted) and was greater in older than younger age groups, greater in men than women, and inversely related to household income. Hoarding was associated with alcohol dependence; paranoid, schizotypal, avoidant, and obsessive-compulsive personality disorder traits; insecurity from home break-ins and excessive physical discipline before 16 years of age; and parental psychopathology. These findings suggest that hoarding may be relatively prevalent and that alcohol dependence, personality disorder traits, and specific childhood adversities are associated with hoarding in the community. KeywordsHoarding; prevalence; risk factors; personality disorders; comorbidity Hoarding behavior has been called "pathological collecting" and is characterized by the acquisition of, and unwillingness or inability to discard, large quantities of seemingly useless objects (Greenberg, Witztum & Levy, 1990;Frost & Gross, 1993). The behavior can lead to significantly cluttered living space in the home and can cause considerable distress and impairment in functioning for individuals and their family members (Tolin, Frost, Steketee, & Fitch, 2008). The clutter may interfere with the normal use of space for basic household activities and increase the risk of injuries due to fire and falling, and illnesses due to poor sanitation Steketee, Frost, & Kim, 2001). *Corresponding author: Jack Samuels, Ph.D., Department of Psychiatry and Behavioral Sciences, Johns Hopkins, University School of Medicine, 600 N. Wolfe Street, Meyer 109, Baltimore, MD 21287-7228. Phone: 410-614-4942. Fax: 410-614-8137, E-mail address: jacks@jhmi.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. To date, hoarding behavior has been studied primarily in samples of individuals who were not selected from the community, such as respondents to advertisements for hoarding research studies, participants in hoarding self-help groups, individuals referred to clinics specializing in the treatment of obsessive-compulsive disorder, and individuals participating in family studies of obsessive-compulsive disorder. Results from these studies suggest that individuals with hoarding behavior have more symptoms of anxiety and depression, a greater prevalence of anxiety disorders, especially generalized anxiety disorder and social phobia, and poorer functioning...