- Metabolic Risk/Epidemiology
- Biologically Informed Polygenic Scores for Brain Insulin Receptor Network Are Associated with Cardiometabolic Risk Markers and Diabetes in Women
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Jannica S. Selenius, Patricia P. Silveira, Mikaela von Bonsdorff, Jari Lahti, Hannu Koistinen, Riitta Koistinen, Markku Seppälä, Johan G. Eriksson, Niko S. Wasenius
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Diabetes Metab J. 2024;48(5):960-970. Published online March 25, 2024
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DOI: https://doi.org/10.4093/dmj.2023.0039
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 Abstract
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- Background
To investigate associations between variations in the co-expression-based brain insulin receptor polygenic score and cardiometabolic risk factors and diabetes mellitus.
Methods
This cross-sectional study included 1,573 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Cardiometabolic markers included body composition, waist circumference, circulating lipids, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 1 and 3 (IGFBP-1 and -3). Glucose and insulin levels were measured during a standardized 2-hour 75 g oral glucose tolerance test and impaired glucose regulation status was defined by the World Health Organization 2019 criteria. Analyzes were adjusted for population stratification, age, smoking, alcohol consumption, socioeconomic status, chronic diseases, birth weight, and leisure-time physical activity.
Results
Multinomial logistic regression indicated that one standard deviation increase in hePRS-IR was associated with increased risk of diabetes mellitus in all participants (adjusted relative risk ratio, 1.17; 95% confidence interval, 1.01 to 1.35). In women, higher hePRS-IR was associated with greater waist circumference and higher body fat percentage, levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein B, insulin, and IGFBP-1 (all P≤0.02). The mePRS-IR was associated with decreased IGF-1 level in women (P=0.02). No associations were detected in men and studied outcomes.
Conclusion
hePRS-IR is associated with sex-specific differences in cardiometabolic risk factor profiles including impaired glucose regulation, abnormal metabolic markers, and unfavorable body composition in women.
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Citations
Citations to this article as recorded by  - A mesocorticolimbic insulin receptor gene co-expression network moderates the association between early life adversity and food approach eating behaviour style in childhood
Angela Marcela Jaramillo-Ospina, Roberta Dalle Molle, Sachin Patel, Shona Kelly, Irina Pokhvisneva, Carolina de Weerth, Patrícia Pelufo Silveira
Appetite.2025; 204: 107762. CrossRef
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