A recent investigation has uncovered new genetic variants linked to normal pressure hydrocephalus (NPH), enhancing our understanding of its genetic landscape and laying the groundwork for deeper exploration of the biological processes involved in the condition.
An extensive study conducted by the University of Eastern Finland and collaborators has discovered novel genetic variants related to normal pressure hydrocephalus (NPH). This research, published in the journal Neurology, marks the first comprehensive genome-wide association study focusing on NPH globally. The findings shed light on the genetic composition of NPH and set the stage for additional studies on the specific biological mechanisms related to the disorder.
NPH is a chronic neurological syndrome that primarily affects older adults, impacting their gait, memory, and bladder function. Currently, shunt surgery is the main treatment option for NPH. The mechanisms behind the disease are still not well understood, and its genetics have only been examined in a limited manner. However, some families have shown a tendency for the idiopathic form of NPH to occur, and prior genetic studies have found specific variants that increase the likelihood of developing NPH.
This research drew on data from the Finnish FinnGen project, which comprises genomic information from Finnish participants, combined with data from health registries. The genome-wide association study involved 1,522 patients with NPH alongside over 450,000 control individuals. For validation, data from the UK Biobank was utilized.
“We sincerely appreciate the contributions of NPH patients and their families to this study,” states Professor Ville Leinonen from the University of Eastern Finland. The process of gathering NPH patients started in Kuopio, Finland, more than 15 years ago. The cohort of NPH patients was expanded through national neurosurgical collaborations, but the success of the current study was largely due to recent partnerships within the FinnGen project.
The research identified key variants associated with NPH across six different gene locations. Several of these genes have previously been linked to brain structures or functions crucial for NPH, including their involvement in the blood-cerebrospinal fluid barrier, the blood-brain barrier, and a connection to an increased size of the brain’s lateral ventricles in the general population—a finding significant for NPH.
“The newly identified gene loci provide a biologically relevant foundation for further investigations into disease mechanisms in NPH,” says Professor Mikko Hiltunen, whose research team works closely with Professor Ville Leinonen’s group at the University of Eastern Finland.
The results align with earlier hypotheses suggesting that NPH is a multifactorial disorder.
