New research by Edith Cowan University (ECU) has shown that better education has a strong genetic correlation and protective causal association with several gut disorders.
The study, published 19 December 2022 in the International Journal of Molecular Sciences, revealed a significant negative global genetic correlation between all cognitive traits and gastrointestinal tract disorders (GIT), including peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), gastritis-duodenitis, irritable bowel syndrome (IBS), and diverticulosis.
Or in other words, higher levels of education and cognitive functioning reduced the risk of gut disorders, and study supervisor Professor Simon Laws, the Director of ECU’s Centre for Precision Health (CPH), said that together with the results of the gene-level overlap analysis, their findings showed evidence of the shared genetic signatures between a range of cognitive traits and GIT conditions.
“We had previously discovered a genetic link between gut health and Alzheimer’s Disease (AD) but could not conclude whether one caused the other,” Professor Laws said.
“Leveraging large-scale genome-wide association studies’ summary statistics [containing the genetic information of more than 766,000 individuals], we comprehensively assessed genetic overlap and potential causality of cognitive traits and Alzheimer’s disease (AD) with several GIT disorders.
“We demonstrate a strong and highly significant inverse global genetic correlation between cognitive traits and GIT disorders including PUD, gastritis-duodenitis, diverticulosis, IBS, and GERD, but not inflammatory bowel disease (IBD).
“Gut disorders and Alzheimer’s may not only share a common genetic predisposition but may be similarly influenced by genetic variations underpinning educational attainment.”
Significantly, higher levels of education and cognitive function provided protection against all the GIT disorders examined in the study, except for inflammatory bowel disease (IBD).
However, further analysis reveals different effects of IBD on cognitive traits and AD at different genomic locations, indicating that this relationship depends on effects at specific locations across the genome.
“This new understanding may explain the lack of significant genetic correlation of IBD with cognitive traits and AD, and the inconsistency reported in previous observational studies,” the authors said, noting that this new insight could shape the direction of future studies.
“For example, some risk genes for AD may be protective against IBD, and vice versa – emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract disorders, however, the mechanisms underlying their relationships remain unclear.”
The study also revealed that certain GIT disorders may influence the brain, with GERD showing evidence of causing a decline in cognitive function across several traits assessed, such as intelligence, cognitive performance, educational attainment, and educational qualification.
Although this is the first study to report this finding, the results support recent research reporting an increased incidence of dementia and GERD, which lead researcher, Dr Emmanuel Adewuyi, believed could assist with earlier diagnoses and potential treatments for patients.
“GERD may be a risk factor for cognitive impairment, so it is important for health workers to look for signs or symptoms of cognitive dysfunction in patients presenting with the gut disorder – this could lead to earlier detection of cognitive decline and therefore earlier interventions aimed at reducing the rate of cognitive decline,” he said.
“We note, however, that this finding (genetic overlap of GERD with a decline in cognitive performance) may only partially contribute to causality, given that environmental factors could also play an important role in this regard.
“For example, individuals with a high level of cognition are likely to be more aware of healthy lifestyles, which may lower their risk of GIT disorders. Conversely, lower quality of life in individuals with GIT disorders may also contribute to impaired cognitive functions.
“More studies are needed to investigate whether treatment for, cure or remission of GERD can contribute to a reduced risk of cognitive decline.”
The likely roles of the immune (autoimmune) system, dysbiosis, enteric amyloid-beta (Aβ) accumulation, inflammatory processes, vagal nerve stimulation, and lipid metabolism have been suggested, however, once again, the mechanisms underlying these relationships require further examination.
Dr Adewuyi said the team’s findings have significant implications for gastrointestinal health.
“The results support education as a possible avenue for reducing the risk of gut disorders by, for example, encouraging higher educational attainment or a possible increase in the length of schooling,” he said.
“Hence, policy efforts aimed at increasing educational attainment or cognitive training may contribute to a higher level of intelligence, which could lead to better health outcomes including a reduced risk of gut disorders.”