Variations in the gene CADM2 may affect both psychological traits and body mass index (BMI), suggesting a genetic link between the two — however, this one gene likely doesn’t affect these characteristics through the same mechanisms, a new study suggests.
The study, “Genetic variation in CADM2 as a link between psychological traits and obesity,” was published in the journal Scientific Reports.
There is a well-established association between obesity and mental illness, but the reasons for this connection are less clear and are likely complex and interconnected, including differences in behavior, hormones, and genetics.
However, exactly how this gene influences these traits is not well understood. The gene could influence both fat storage/metabolism and psychological traits independently, or it could directly influence psychological traits only, but in a way that predisposes a person towards obesity, even if there isn’t a direct effect on obesity.
For example, it’s been proposed that CADM2 variations could increase risk-taking behavior, which could lead to less healthy choices that ultimately result in obesity.
In this study, researchers set out to systemically analyze the relationship between CADM2, obesity, and psychological traits. They focused on single nucleotide polymorphisms (SNPs) in the CADM2 gene. SNPs are substitutions of one nucleotide (the “letters” of the genetic code) for another.
To do this, the researchers used several databases that include SNP information.
To assess the relationship between the CADM2 gene and psychological traits, they used data from the UK Biobank, which includes genetic data and psychological information (in the form of answers to standardized questionnaires) for more than 500,000 people from the U.K.
The researchers note that such questionnaires are “imperfect ways to measure psychological traits,” but they argue that the questions asked have been reasonably validated to be associated with actual traits and mental illnesses.
For obesity and related traits, the researchers analyzed three databases: IMPROVE, which includes 3,711 people from across Europe with many risk factors for cardiovascular disease (e.g. smoking, high blood pressure, etc.); SCARFSHEEP, which has data for Swedish people who experienced a heart attack before the age of 60 and case-matched controls, totaling 2,513 people; and PROCARDIS, which has data for 5,688 individuals with coronary artery disease and 2,310 controls without the disease.
As expected, a number of CADM2 SNPs were associated with the analyzed traits; for example, 908 SNPs were found to have a statistically significant association with BMI, and 809 were associated with risk-taking behavior.
But were these associations results of the same effect or multiple different effects?
Of course, the data analyzed only shows associations — correlation isn’t causation — but analyses suggest the latter. These analyses are somewhat complex, but the general idea is that some SNPs are associated with only psychological or metabolic traits, and individual SNPs can be removed from the analysis without causing much change in the observed associations.
The researchers also analyzed data from another database, GTEx, which contains data for how individual SNPs for genes change the expression of the proteins those genes encode for within various tissues in the human body.
The most striking observation was that some SNPs in the CADM2 gene had a greater effect on CADM2 protein levels in the brain, whereas others seemed to have a more pronounced effect on the level of protein in fat tissue. This suggests a plausible, if preliminary, mechanism for how variations in this one gene could affect multiple traits separately.
“In conclusion,” the researchers wrote, “we have conducted a systematic, large-scale analysis of multiple datasets providing evidence that CADM2 represents a putative shared biological link between metabolic and psychological disorders.”
Further studies, particularly in animal models where cause-and-effect relationships can be teased out by experimentation, will be needed to further elucidate how CADM2 affects both body weight and psychological traits.
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