MedElevator Войти в исследования
← Поиск публикаций

DOI 10.1038/s42003-025-08674-9

Медицинская библиотека · Communications biology · 2025

Association of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program.

Sarnowski Chloé, Zhang Yixin, Ammous Farah, Shade Lincoln M P, DiCorpo Daniel, Jian Xueqiu, Arnett Donna K, Austin Thomas R, Beiser Alexa, Bis Joshua C, Blangero John, Boerwinkle Eric, Bressler Jan, Curran Joanne E, DeCarli Charles S, Doddapaneni Harsha, Dupuis Josée, Fardo David W, Florez Jose C, Gabriel Stacey, Gibbs Richard A, Glahn David C, Gupta Namrata, González Hector M, González Kevin A, Hatzikotoulas Konstantinos, Hayden Kathleen M, Heckbert Susan R, Hidalgo Bertha, Huerta-Chagoya Alicia, Hughes Timothy M, Kardia Sharon L R, Kooperberg Charles L, Launer Lenore J, Longstreth W T, T2DGGI consortium, MAGIC consortium, Mandla Ravi, Mathias Rasika A, Morris Andrew P, Mosley Thomas H, Nasrallah Ilya M, Nyquist Paul, Psaty Bruce M, Qi Qibin, Raffield Laura M, Rayner Nigel W, Reiner Alexander P, Satizabal Claudia L, Selvin Elizabeth, Sevilla-Gonzalez Magdalena D R, Smith Albert V, Smith Jennifer A, Smith Kirk, Snively Beverly M, Southam Lorraine, Sofer Tamar, Suzuki Ken, Taylor Henry J, Udler Miriam S, Viaud-Martinez Karine A, Wassertheil-Smoller Sylvia, Wood Alexis C, Yanek Lisa R, Yin Xianyong, Manning Alisa K, Rotter Jerome I, Rich Stephen S, Meigs James B, Fornage Myriam, Seshadri Sudha, Morrison Alanna C, TOPMed Diabetes working group, and the TOPMed Neurocognitive working group

СтатьяПеревод в очереди

Аннотация

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 (PEA = 3.0 × 10-8) fasting insulin PSs with total cranial volume, and of a metabolic syndrome European PS with general cognitive function (BEA = -0.13, PEA = 0.0002) and lateral ventricular volume (BEA = 0.09, PEA = 0.002). We identify suggestive negative associations (P < 0.007) of metabolic syndrome and obesity pPSs with general cognitive function, and of lipodystrophy pPSs with total cranial volume. A higher genetic predisposition to IR is associated with lower brain size, and a genetic predisposition to specific IR-related type 2 diabetes subtypes, such as metabolic syndrome and mechanisms of IR mediated through obesity and lipodystrophy, is potentially involved in cognitive decline.

Для цитирования: Sarnowski Chloé, Zhang Yixin, Ammous Farah, Shade Lincoln M P, DiCorpo Daniel, Jian Xueqiu, Arnett Donna K, Austin Thomas R, Beiser Alexa, Bis Joshua C, Blangero John, Boerwinkle Eric, Bressler Jan, Curran Joanne E, DeCarli Charles S, Doddapaneni Harsha, Dupuis Josée, Fardo David W, Florez Jose C, Gabriel Stacey, Gibbs Richard A, Glahn David C, Gupta Namrata, González Hector M, González Kevin A, Hatzikotoulas Konstantinos, Hayden Kathleen M, Heckbert Susan R, Hidalgo Bertha, Huerta-Chagoya Alicia, Hughes Timothy M, Kardia Sharon L R, Kooperberg Charles L, Launer Lenore J, Longstreth W T, T2DGGI consortium, MAGIC consortium, Mandla Ravi, Mathias Rasika A, Morris Andrew P, Mosley Thomas H, Nasrallah Ilya M, Nyquist Paul, Psaty Bruce M, Qi Qibin, Raffield Laura M, Rayner Nigel W, Reiner Alexander P, Satizabal Claudia L, Selvin Elizabeth, Sevilla-Gonzalez Magdalena D R, Smith Albert V, Smith Jennifer A, Smith Kirk, Snively Beverly M, Southam Lorraine, Sofer Tamar, Suzuki Ken, Taylor Henry J, Udler Miriam S, Viaud-Martinez Karine A, Wassertheil-Smoller Sylvia, Wood Alexis C, Yanek Lisa R, Yin Xianyong, Manning Alisa K, Rotter Jerome I, Rich Stephen S, Meigs James B, Fornage Myriam, Seshadri Sudha, Morrison Alanna C, TOPMed Diabetes working group, and the TOPMed Neurocognitive working group. Association of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program.. Communications biology. 2025. DOI: 10.1038/s42003-025-08674-9.

Предметные рубрики MeSH

HumansMaleInsulin ResistanceMiddle AgedFemalePrecision MedicineCross-Sectional StudiesAgedMetabolic SyndromeAdult
Подготовка и перевод публикации
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

Тип публикации указан по данным источника. Уровень доказательности автоматически не присваивается.