A study has found that even the same genetic mutation can lead to different outcomes depending on whether it was inherited from the father or the mother. Depending on the gene, this can result in opposing outcomes, such as an increased or decreased risk of diabetes.
The research team led by Professor Zoltán Kutalik of the University of Lausanne in Switzerland noted, "After analyzing genetic data from up to 236,781 individuals, we discovered a 'bipolar effect' that causes outcomes to vary depending on whether the variant gene was inherited from the father or the mother," in an announcement published in the international journal Nature on July 7.
The research team analyzed genetic data from 109,385 individuals registered in the UK Biobank and found about 30 variant genes that have different effects based on the parental genetic pathway. Of these, 19 exhibited the bipolar effect that leads to opposing results. The bipolar effect refers to when the outcome differs for children depending on which parent they inherited the gene from.
For example, the rs10838787 gene variant increased the risk of developing type 2 diabetes by 14% when inherited from the father, whereas inheriting it from the mother resulted in a 9% decrease in risk. Type 2 diabetes occurs when the hormone insulin does not properly secrete or function to absorb sugar in the blood.
Bipolar effects were also observed in two genes (rs2293607 and rs11100479) related to the length of telomeres, which are located at the ends of chromosomes. When inherited from the father, rs2293607 resulted in shorter telomere lengths, whereas rs11100479 led to longer telomere lengths when inherited from the father. Telomeres are associated with aging and lifespan, and they tend to shorten with age, making them more susceptible to genetic mutations.
The research team used genetic data from 85,050 individuals registered in the Estonian Biobank and 42,346 individuals from the Norwegian Biobank to verify whether the bipolar effects of these genes observed in other countries. They confirmed that approximately 87% showed similar outcomes to those in the UK.
The research team stated, "Previous studies had to rely on parental and offspring genetic data and detailed household trees, limiting them to small-scale research. However, this study is significant because it developed a method to estimate parental-derived genes without parental genetic data, allowing for the discovery of bipolar effects in a large population."
References
Nature (2025), DOI: https://doi.org/10.1038/s41586-025-09357-5