Genetic architecture of ADHD and overlap with other psychiatric disorders and cognition-related phenotypes.

Attention-deficit/hyperactivity disorder (ADHD) co-occurs with many other psychiatric disorders and traits. In this review, we summarize and interpret the existing literature on the genetic architecture of these comorbidities based on hypothesis-generating approaches. Quantitative genetic studies indicate that genetic factors play a substantial role in the observed co-occurrence of ADHD with many different disorders and traits. Molecular genetic correlations derived from genome-wide association studies and results of studies based on polygenic risk scores confirm the general pattern but provide effect estimates that are smaller than those from twin studies. The identification of the specific genetic variants and biological pathways underlying co-occurrence using genome-wide approaches is still in its infancy. The first analyses of causal inference using genetic data support causal relationships between ADHD and comorbid disorders, although bidirectional effects identified in some instances point to complex relationships. While several issues in the methodology and inferences from the results are still to be overcome, this review shows that the co-occurrence of ADHD with many psychiatric disorders and traits is genetically interpretable.
Competing Interests: Declaration of Competing Interest In the past year, S Faraone received income, potential income, travel expenses continuing education support and/or research support from Rhodes, OnDosis, Tris, Otsuka, Arbor, Ironshore, KemPharm/Corium, Akili, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child’s Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is Program Director of www.adhdinadults.com. H Larsson reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals and Evolan Pharma AB; and sponsorship for a conference on attention-deficit/hyperactivity disorder from Shire/Takeda Pharmaceuticals and Evolan Pharma AB, all outside the submitted work. J Kuntsi has given talks at educational events sponsored by Medice; all funds are received by King’s College London and used for studies of ADHD. B Franke has received educational speaking fees from Medice; all funds were received by Radboud University Medical Center and used for research. JA Ramos-Quiroga was on the speakers’ bureau and/or acted as consultant for Biogen, Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the last 3 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 3 years: Janssen-Cilag, Shire, Oryzon, Roche, Psious, and Rubió. D Demontis has received speaker fee from Medici Nordic. AD Børglum has received speaker fee from Lundbeck. The rest of the authors do not declare any conflict of interest.
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