A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10–11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10–10, OR = 1.63) and 17q12-21 (P = 1.7 × 10–10, OR = 1.38).

No abstract

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

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In 1997, Putnam [1] pointed out that relatively little was known about the etiology and development of dissociation other than the presumed etiologic role of trauma; however, the fact that nontraumatized individuals sometimes demonstrated dissociation and that not all trauma survivors dissociate suggested that there may be more to the etiology and development of dissociation than trauma alone. Putnam [1] explored the role of various potential moderating variables including age, sex, culture, genetic factors, and education/intelligence in the development of dissociation, and although moderating trends were found for some of these variables, existing research has not convincingly demonstrated that any of these variables significantly influence dissociation.Family environmental factors, however, are the one set of factors that have been most consistently related to dissociation. Factors such as inconsistent parenting or disciplining, [2-4] level of family risk [5], and parental dissociation, as measured by the Dissociative Experiences Scale [6], have been shown to be associated significantly with higher levels of dissociation in adulthood. Most available research on dissociation, however, has focused on trauma, leaving many unanswered questions regarding how other family factors intersect with familial abuse in the developmental trajectories leading to dissociative disorders.Barach [7] was one of the first theorists to connect dissociation with attachment theory. In his article, Barach [7] suggested that multiple personality disorder (now known as dissociative identity disorder) was a variant of an "attachment disorder." He pointed out that individuals who had this disorder tended to demonstrate the extreme detachment, or emotional unresponsiveness, experienced by children faced with a loss of their primary caretaker, as described by Bowlby [8]. Barach [7] further suggested that children of unresponsive caretakers were also likely to engage in dissociative or "detached" behaviors. As one offshoot of attachment studies, developmental theorists and researchers have begun to explore the role of early childhood attachment and parenting in the etiology and development of dissociative symptomatology.Liotti's [9] theorizing has more specifically implicated disorganized patterns of infant attachment behavior as potential precursors to the development of dissociation later in life. He pointed out that there are parallels between infant disorganization and dissociation. Both phenomena reflect a pervasive lack of behavioral or mental integration. This primary failure of integration in infancy may result in vulnerability to dissociative organization of mental life