New Research on Genetic Origin of ADHD

A study in Lancet October 23 has added significant evidence to the growing knowledge that Attention Deficit Hyperactivity Disorder (ADHD) is largely biological.  Non-genetic causes such as abnormal brain development, brain injury or environmental factors are also believed to play a role in the disorder, but this latest study suggests brains of some children with ADHD develop differently from those of other children.

We have known that ADHD has a large heritability from studies showing that if a person has ADHD, then:

  • an identical twin has a 78-92% chance of having ADHD.
  • 25-35% of siblings have ADHD.
  • 15-20% of the mothers have ADHD.
  • 25-30% of the fathers have ADHD.

From a different angle, if a parent has ADHD, there is a 20-54% chance that his/her child will also get ADHD.

More specifically, since ADHD often appears to run in families, research has suggested that there may be a genetic component to this disorder.  ADHD is a complex disorder that probably involves at least two genes–and many, many sites on those genes. Twin and family studies of ADHD show a substantial genetic heritability with little or no family environmental effect. Linkage and association studies have conclusively implicated the dopamine transporter gene (DAT1). DAT1 has also been confirmed as being associated with bipolar disorder. Remarkably, and for the first time in psychiatry, genetic markers at the DAT1 locus appear to be able to predict clinical heterogeneity because the non-conduct disordered subgroup of ADHD is associated with DAT1 whereas other subgroups do not appear to be associated. The second most well replicated susceptibility gene encodes the DRD4 dopamine receptor and many other dopamine related genes appear to be implicated. It is becoming increasingly clear that genes causing bipolar mania overlap with genes for a subtype of ADHD. The key to understanding the genetics of ADHD is to accept very considerable heterogeneity with different genes having effects in different families and in different individuals.

The new research by Nigel Williams and colleagues at the MRC Centre for Neuropsychiatric Genetics at Cardiff University School of Medicine in Cardiff, Wales shows that children with ADHD have larger genetic variations than controls.  The details are arcane, but are based on the number of copy number variants (CNVs), which are duplications or deletions in the genome.

Also important for the public is that these findings are essentially strong statistical findings but have little utility in diagnosing specific individuals at this time.  For instance, this study compared data on single nucleotide polymorphisms from 366 children in the UK who met DSM-IV criteria for ADHD with data from 1,047 controls.  14% of children with ADHD carried a large CNV, versus 7% among controls.

Again, that’s strong statistical evidence for heritability, but doesn’t account for 86% of the children with ADHD. That’s why Williams et al have published their article with the title: “Rare Chromosomal Deletions and Duplications in Attention-Deficit Hyperactivity Disorder.”

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