From the Guidelines
ADHD has a strong genetic component, with heritability estimated at 70-80%, and is considered a polygenic disorder, meaning many genes each contribute small effects rather than a single gene causing the condition. The genetics of ADHD are complex, involving multiple genes that affect dopamine and norepinephrine neurotransmission, such as DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25 1. These genes influence how neurotransmitters function in the brain, affecting attention, impulse control, and executive functioning. Environmental factors like prenatal exposure to toxins, premature birth, and low birth weight can interact with genetic predispositions, contributing to the development of ADHD. Family studies show that if a parent has ADHD, their child has a 25-50% chance of developing it, and if one identical twin has ADHD, the other has a 70-80% chance of also having it 1. Understanding the genetic basis of ADHD helps explain why it often runs in families and why medications targeting dopamine and norepinephrine systems are effective treatments.
Some key points to consider when evaluating the genetics of ADHD include:
- The heritability of ADHD is estimated to be 70-80% 1
- Multiple genes are involved in the development of ADHD, including those affecting dopamine and norepinephrine neurotransmission 1
- Environmental factors can interact with genetic predispositions to contribute to the development of ADHD 1
- Family studies show a strong correlation between ADHD in parents and children, as well as between identical twins 1
Overall, the genetics of ADHD are complex and multifaceted, and understanding the genetic basis of the disorder can help inform diagnosis and treatment. The most recent and highest quality study, published in 2022, supports the idea that ADHD is a polygenic disorder with a strong genetic component 1.
From the Research
Genetics of ADHD
- ADHD shows consistently high heritability in genetic research, with a heritability of about 80% 2, 3.
- The proportion of heritability based on single nucleotide variants is estimated to be around 22% 2, 3.
- Common variants derived from mega genome-wide association analyses (GWAS) usually display small effect sizes and explain only a small fraction of phenotypic variance 2.
- Rare variants, on the other hand, display large effect sizes but explain a small fraction of phenotypic variance due to their rareness 2.
Genetic Risk Variants
- Frequent variants in genome-wide association study data explain only little variance 3.
- Rare genetic syndromes show higher prevalence for ADHD, indicating a potential role for a small number of patients 3.
- Polygenic risk scores (PRS) could potentially be applied to every patient and explain different behavioral phenotypes in ADHD 2, 3.
Specific Genes
- The dopamine transporter gene (DAT1) has been implicated in ADHD and is associated with the non-conduct disordered subgroup of ADHD 4.
- The DRD4 dopamine receptor gene is also a well-replicated susceptibility gene for ADHD 4.
- Other dopamine-related genes appear to be implicated in ADHD, and genes causing bipolar mania overlap with genes for a subtype of ADHD 4.
- A study identified 105 genes associated with ADHD, with 14 genes clustering within an interactive gene network and showing enrichment in nitric oxide synthase and alpha-1 adrenergic pathways 5.
Biological Pathways
- Genome-wide association studies have implicated several genetic loci at the genome-wide level of statistical significance and show that about a third of ADHD's heritability is due to a polygenic component comprising many common variants each having small effects 6.
- Copy number variants account for part of ADHD's heritability and have implicated new biological pathways that may eventually have implications for treatment development 6.