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Biologically Informed Polygenic Scores for Brain Insulin Receptor Network Are Associated with Cardiometabolic Risk Markers and Diabetes in Women (2024)


Selenius, J. S., Silveira, P. P., Bonsdorff, M. V., Lahti, J., Koistinen, H., Koistinen, R., Seppälä, M., Eriksson, J. G., & Wasenius, N. S. (2024). Biologically Informed Polygenic Scores for Brain Insulin Receptor Network Are Associated with Cardiometabolic Risk Markers and Diabetes in Women. Diabetes & Metabolism Journal, Early online. https://doi.org/10.4093/dmj.2023.0039


JYU-tekijät tai -toimittajat


Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajatSelenius, Jannica S.; Silveira, Patricia P.; Bonsdorff, Mikaela von; Lahti, Jari; Koistinen, Hannu; Koistinen, Riitta; Seppälä, Markku; Eriksson, Johan G.; Wasenius, Niko S.

Lehti tai sarjaDiabetes & Metabolism Journal

ISSN2233-6079

eISSN2233-6087

Julkaisuvuosi2024

Ilmestymispäivä25.03.2024

VolyymiEarly online

KustantajaKorean Diabetes Association

JulkaisumaaKorean tasavalta (Etelä-Korea)

Julkaisun kielienglanti

DOIhttps://doi.org/10.4093/dmj.2023.0039

Julkaisun avoin saatavuusAvoimesti saatavilla

Julkaisukanavan avoin saatavuusKokonaan avoin julkaisukanava

Julkaisu on rinnakkaistallennettu (JYX)https://jyx.jyu.fi/handle/123456789/94530


Tiivistelmä

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.


YSO-asiasanatdiabetessydän- ja verisuonitauditriskitekijätbiomarkkeritrasva-aineenvaihduntakehonkoostumussukupuolierot

Vapaat asiasanatcardiometabolic risk factors; diabetes mellitus; lipid metabolism


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OKM-raportointiKyllä

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Viimeisin päivitys 2024-29-04 klo 08:02