Original Article A genetic analysis of the validity of the Hypomanic Personality Scale Johnson SL, Carver CS, Joormann J, Cuccaro M. A genetic analysis of the validity of the Hypomanic Personality Scale. Bipolar Disord 2015: 17: 331–339. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives: Studies of mania risk have increasingly relied on measures of subsyndromal tendencies to experience manic symptoms. The measures of mania risk employed in those studies have been shown to predict manic onset, to show familial associations, and to demonstrate expected correlations with psychosocial variables related to bipolar disorder. However, little work has been conducted to validate such measures against biologically relevant indices, or to consider whether early adversity, which has been shown to be highly elevated among those with bipolar disorder, is related to higher scores on mania risk measures. This study tested whether a well-used, self-report measure of vulnerability to mania is associated with several candidate genes that have previously been linked with bipolar disorder or with early adversity. Interactions of genes with early adversity in the prediction of mania vulnerability were also tested. Methods: Undergraduate students from the University of Miami (Coral Gables, FL, USA) (N = 305) completed the Hypomanic Personality Scale and the Risky Families Scale, and provided blood for genotyping. Results: Findings indicated that the Hypomanic Personality Scale was related to a number of dopamine-relevant polymorphisms and with early adversity. A polymorphism of ANKK1 appeared to specifically increase mania risk in the context of early adversity. Conclusions: These results provide additional support for the validity of the Hypomanic Personality Scale. Sheri L Johnson a,b , Charles S Carver c , Jutta Joormann c,d and Michael Cuccaro e a Department of Psychology, University of California, Berkeley, Berkeley, CA, b Center for Advanced Study in the Behavioral Sciences, Palo Alto, CA, c Department of Psychology, University of Miami, Coral Gables, FL, d Department of Psychology, Yale University, New Haven, CT, e Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA doi: 10.1111/bdi.12251 Key words: bipolar disorder – dopamine – early adversity – genetic polymorphism – mania risk Received 23 January 2014, revised and accepted for publication 27 June 2014 Corresponding author: Dr. Sheri L. Johnson Department of Psychology University of California, Berkeley 3210 Tolman Hall Berkeley, CA 94720-1650 USA E-mail: sljohnson@berkeley.edu Several different measures have been developed to assess risk for mania, including the General Behav- ior Inventory (GBI) (1), the Temperament Evalua- tion of Memphis, Pisa, Paris, and San Diego (2), and the Hypomanic Personality Scale (HPS) (3). Each of these measures assesses tendencies towards subsyndromal manic symptoms as well as person- ality traits thought to be related to bipolar disorder (BD), such as positive affectivity. Substantial evi- dence has accrued that the HPS and the GBI prospectively predict the onset of diagnoses of BD. For example, over a 13-year follow-up period, 73% of persons at high risk for mania as defined by the HPS developed diagnosable symptoms of bipolar spectrum disorder (4). Moreover, a sub- stantial body of research indicates that many of the psychosocial variables that predict the course of mania within BD are also robustly correlated with these measures of mania risk (5–7). These measures of risk provide an opportunity to study basic risk factors without the confounding influ- ence of the lifestyle, health, and medication changes that emerge as bipolar symptoms reach a diagnosable level. Surprisingly, researchers have not determined whether genetic or early adversity correlates of mania risk measures parallel those that have been documented as relevant to bipolar diagnoses. The goal of the study reported here was to consider whether one commonly used, well-validated mea- sure of mania, the HPS, demonstrates an associa- tion with genetic polymorphisms related to BD 331 Bipolar Disorders 2015: 17: 331–339 © 2014 John Wiley & Sons A/S Published by John Wiley & Sons Ltd. BIPOLAR DISORDERS