attention-deficit hyperactivity disorder and adult schizophrenia Shared polygenic contribution between childhood

Large-scale genetic association studies have identified replicable susceptibility alleles for some psychiatric phenotypes. 1 This includes both common and rare variants. A striking finding has been that susceptibility variants identified to date often confer susceptibility to more than one of the traditional clinical phenotypes , a finding that has the potential to increase understanding of the biological relationship between these traditional diagnostic categories. 1–3 The focus of this study is childhood attention-deficit hyperactivity disorder (ADHD) and its potential genetic relationship to adult schizophrenia and bipolar disorder. There is evidence of some degree of shared genetic susceptibility between schizophrenia and childhood ADHD for rare chromosomal variants. 4 In the present study, we have considered another possible source of genetic overlap, namely common single nucleotide polymorphisms (SNPs) and we have extended the analysis to consider bipolar disorder as well as schizophrenia. The only prior study that has started to examine this, selected six bipolar genetic risk variants and identified no strong association with ADHD or with scores on the Mood Disorder Questionnaire. 5 Here, we have used a more powerful, genome-wide approach and examined whether, when they are considered en masse using polygenic score analysis, 6 multiple schizophrenia 7 and bipolar disorder 8 common risk alleles contribute to ADHD risk. Method In general, we followed the polygenic score analysis approach described by the International Schizophrenia Consortium (ISC). 6 The basic principle of that analysis was that a set of many alleles that discriminated case status in a 'discovery' schizophrenia case–control sample, also significantly discriminated case status in an independent 'target' schizophrenia case–control sample. We used the published Psychiatric Genome-wide Association Study (GWAS) Consortium (PGC) data-sets (schizophrenia and bipolar disorder) as two separate discovery sets and our ADHD data as the target set. Sample Discovery data We made use of the PGC schizophrenia 7 and bipolar disorder 8 case–control data-sets. The schizophrenia sample comprised 9394 cases and 12 462 controls analysed at 1 252 901 SNPs. The bipolar disorder sample comprised 7481 cases and 9250 controls analysed at 2 427 089 SNPs. These studies contain individuals of European origin collected across Europe, the USA, and Australia. We note that there are a number of control individuals that contribute to both the PGC schizophrenia and bipolar disorder samples, including the Wellcome Trust Case Control Consortium (WTCCC) – Phase 1 control sample. We interrogated genotype data from a UK/Irish ADHD GWAS. 10 The sample comprises …