Genetic study identifies migraine causes and promising therapeutic targets

QUT genetic researchers have found blood proteins that cause migraine and have a shared link with Alzheimer’s disease that could potentially be prevented by repurposing existing therapeutics.

Findings from the genetic analyses were published in Nature Communications by Professor Dale Nyholt and his Ph.D. candidate Hamzeh Tanha from the QUT Center for Genomics and Personalized Health.

Professor Nyholt said the study identified causal genetic links between migraine risk and altered levels of five blood proteins:

  • Lower levels of FARS2, GSTA4 and CHIC2 proteins linked to inflammation and migraine.
  • Higher levels of DKK1 and PDGFB proteins inhibit Wnt signaling pathways and have links to brain calcification disorders.
  • The risk-increasing effect of DKK1 provides a potential mechanistic link between the previously reported associations between migraine, Alzheimer’s disease (AD), and cerebral amyloid angiopathy (CAA).

Professor Nyholt said people with migraine had higher levels of DKK1 and PDGFB, and lower levels of FARS2, GSTA4 and CHIC2 that causally increased their risk of migraine.

He said higher levels of DKK1 and PDGFB blood proteins inhibited Wnt signaling pathways that pass biological signals into cells and could lead to brain calcification as well as inflammation causing pain, while lower levels of antioxidant blood proteins FARS2, GSTA4 and CHIC2 also caused inflammation linked to migraine.

“Notably, our finding of a strong causal effect of higher levels of DKK1 on migraine risk might be linked to a reduction in Wnt signaling as observed in Alzheimer’s disease and cerebral amyloid angiopathy,” Professor Nyholt said.

“Cerebral amyloid angiopathy is a build-up of proteins in brain arteries known to cause Alzheimer’s disease and reduced Wnt signaling has also been shown to increase neuropathic pain in a rat model.”

Medical Xpress, (2022, May 12, 2022) Genetic study identifies migraine causes and promising therapeutic targets