Update on genetics of attention deficit/hyperactivity disorder: current status 2023.

Abstract

Attention deficit/hyperactivity disorder (ADHD) shows consistently high heritability in genetic research. In this review article, we give an overview of the analysis of common and rare variants and some insight into current genetic methodology and their link to clinical practice. The heritability of about 80% is also high in comparison to other psychiatric diseases. However, recent studies estimate the proportion of heritability based on single nucleotide variants at 22%. The hidden heritability is an ongoing question in ADHD genetics. Common variants derived from mega genome-wide association analyses (GWAS) and subsequent meta-analyses usually display small effect sizes and explain only a small fraction of phenotypic variance. Rare variants, on the contrary, not only display large effect sizes but also rather explain, due to their rareness, a small fraction on phenotypic variance. Applying polygenic risk score (PRS) analysis is an improved approach of combining effect sizes of many common variants with clinically relevant measures in ADHD. We provide a concise overview on how genetic analysis, with a focus on GWAS and PRS, can help explain different behavioural phenotypes in ADHD and how they can be used for diagnosis and therapy prediction. Increased sample sizes of GWAS, meta-analyses and use of PRS is increasingly informative and sets the course for a new era in genetics of ADHD.