Researchers have conducted a comprehensive genetic analysis to estimate the polygenic genetic overlap between 316 unique blood metabolite levels and migraine risk.
A migraine is a highly prevalent brain disorder which consists of episodic, severe headaches. The World Health Organisation (WHO) estimates that the lifetime prevalence of migraines is 14% and that around 3,000 migraine attacks per million people occur worldwide every day. Not only are migraines costly to society, they are also economically damaging, with the overall costs estimated to be up to €27 billion in Europe and $20 billion in the US.
Both the risk of migraine and blood metabolite levels are thought to be somewhat due to genetic factors. Metabolites are the result of the interaction of an organism’s genome with its environment. They are required for growth, maintenance and normal function. The metabolome is defined as the total collection of metabolites present in an organism. Blood metabolite levels are thought to be up to 80% heritable. In addition, genome-wide association studies (GWAS) have identified that the heritability of migraine mutations could be over 10%.
Therefore, the study of the blood metabolome in migraines could provide insights into the metabolites underlying the disease. Understanding the shared genetic factors between blood metabolites and migraines could help to predict the risk of the disease and create a pathway for the development of effective preventative treatment options.
Shared genetics of migraines and the blood metabolome
Recently, a group of researchers from QUT Centre for Genomics and Personalised Health conducted comprehensive genetic analyses to estimate the polygenic genetic overlap between 316 unique blood metabolite levels and migraine risk at both genome-wide and loci levels. The team then identified pleiotropic genes involved in any genetic overlaps and inferred the causal effects of the metabolic traits on migraines. Their findings were published in The American Journal of Human Genetics.
The team revealed significant genome-wide overlaps between migraines and 44 metabolites. Moreover, 36 metabolites were identified that had shared genetic influences with migraines at eight independent genomic loci. Notably, the team found causal genetic links to three blood metabolite levels that increased migraine risk. These included: (1) lower levels of docosahexaenoic acid (DHA – the end product of omega-3 fatty acids), (2) higher levels of lysophosphatidylethenolamine 20:40 (LPE(20:4) – a lipid metabolite), and (3) lower levels of an uncharacterised metabolite named X-11315.
Further exploring metabolites and migraines
Overall, this exploration of the genetic overlap between metabolic traits and migraines has identified that fatty acids are genetically associated with migraine risk. The results suggest that higher levels of fatty acids, except for DHA, are present in individuals with migraines. Additionally, longer-chain fatty acids, such as DHA, may play a protective role against migraines.
It is important that the observed genetic links are further explored and clinical trials are carried out to test compounds that may influence metabolite levels and prevent migraines. For example, LPE(20:4) could act as a therapeutic target for migraines, or the consumption of DHA may benefit individuals with migraines. Continued research on the importance of lipids in migraine biology will be paramount to shift these discoveries into clinically relevant findings.
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