biostudies-literatureSarnowski CNIA NIH HHS1352https://www.ebi.ac.uk/biostudies/studies/S-EPMC12460837biostudies-literatureUnknown8(1)To better characterize the potential biological mechanisms underlying insulin resistance (IR) and dementia, we derive cross-population and population specific polygenic scores [PSs] for fasting insulin and IR-related partitioned PSs [pPSs]. We conduct a cross-sectional study of the associations of these genetic scores with neurological outcomes in >17k participants (36% men, mean age 55 yrs) from the Trans-Omics for Precision Medicine (TOPMed) program (50% Non-Hispanic White, 23% Black/African American, 21% Hispanic/Latino American, and 4% Asian American). We report significant negative associations (P < 0.002) of the cross-population (P = 1.3 × 10^-5) and European (P_EA = 3.0 × 10^-8) fasting insulin PSs with total cranial volume, and of a metabolic syndrome Communications biologyAssociation of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program.PMC12460837R00 AG066849Psaty BMManning AKDupuis JFlorez JCKardia SLRRotter JIBressler JGibbs RABoerwinkle ERich SSMorrison ACMandla RMosley THCurran JEGabriel SHughes TMGupta NHayden KMT2DGGI consortiumTOPMed Diabetes working groupMAGIC consortiumRaffield LMWassertheil-Smoller SWood ACHuerta-Chagoya ANasrallah IMDiCorpo DAmmous FDeCarli CSFardo DWFornage MSarnowski CUdler MSJian XYanek LRViaud-Martinez KANyquist PMeigs JBBeiser ABlangero JGonzalez KASuzuki KTaylor HJSatizabal CLQi QKooperberg CLSelvin ESnively BMSofer TSmith AVArnett DKGlahn DCSmith JAMorris APDoddapaneni HSoutham LYin XReiner APAustin TRHatzikotoulas KHidalgo BHeckbert SRSmith KLongstreth WTSeshadri SRayner NWBis JCMathias RAand the TOPMed Neurocognitive working groupSevilla-Gonzalez MDRZhang YShade LMPLauner LJGonzalez HMfalseAssociation of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program.To better characterize the potential biological mechanisms underlying insulin resistance (IR) and dementia, we derive cross-population and population specific polygenic scores [PSs] for fasting insulin and IR-related partitioned PSs [pPSs]. We conduct a cross-sectional study of the associations of these genetic scores with neurological outcomes in >17k participants (36% men, mean age 55 yrs) from the Trans-Omics for Precision Medicine (TOPMed) program (50% Non-Hispanic White, 23% Black/African American, 21% Hispanic/Latino American, and 4% Asian American). We report significant negative associations (P < 0.002) of the cross-population (P = 1.3 × 10^-5) and European (P_EA = 3.0 × 10^-8) fasting insulin PSs with total cranial volume, and of a metabolic syndrome 2025-01-01T00:00:00Z2025 Sep2026-06-03T20:09:20.429Z2026-05-31T03:07:27.135ZS-EPMC124608374099318210.1038/s42003-025-08674-9