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  • Ovid Technologies (Wolters Kluwer Health)  (4)
  • 1
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    Online Resource
    Abstract 18931: Integrative Genomics Analyses Identifies Shared Regulatory Networks for Cardiovascular Disease and Type 2 Diabetes Mellitus in American Women of Caucasian, African and Hispanic Ethnicities
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Circulation Vol. 132, No. suppl_3 ( 2015-11-10)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 132, No. suppl_3 ( 2015-11-10)
    Abstract: Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) have many shared risk factors, suggesting that they have common pathophysiological mechanisms. Our recent analysis of genome wide association studies (GWAS) of both CVD and T2D in three ethnic populations revealed a number of biological pathways, such as extracellular matrix and focal adhesion, to be genetically associated with both diseases. Building on our prior work employing knowledge-driven pathways, we performed data-driven integrative genomics analyses using gene co-expression networks constructed from a multitude of tissue-specific transcriptome datasets in conjunction with GWAS for CVD, T2D, and a vascular disease phenotype (VD, representing combined CVD+T2D) in three different ethnic groups of 8155 African Americans, 3494 Hispanic Americans and 3697 Caucasian Americans participated in the national Women’s Health Initiative (WHI) study. We examined a total of 2674 coexpression networks and found that 24 modules were significantly enriched for GWAS signatures for all three disease end points (15 modules) or VD only (9 modules) across multiple cohorts at false discovery rate 〈 5%. These modules were enriched for the previously identified pathways like focal adhesion. Further, top modules for all three diseases were enriched for genes involved in citrate cycle and G-protein coupled receptor signaling, whereas top modules for VD were related to amino acid metabolism and BMP signaling, indicating novel processes that are shared between CVD and T2D. To pinpoint key driver (KD) for these modules, we integrated Bayesian networks of adipose, brain, kidney, liver and muscle tissue, and identified highly significant KDs such as BCL6B in adipose, MALAT1 in brain, ZNF565 in kidney, GLS2 in liver and MYL2 in muscle. Among the top KDs, MALAT1, GLS2 and MYL2 have been previously implicated in CVD and T2D, whereas the others represented novel findings. In summary, by leveraging multi-ethnic GWAS data on CVD and T2D and data-driven transcriptional networks, we uncovered both known and novel regulatory mechanisms that appeared to be shared by the two vascular diseases. These network regulators revealed may serve as important targets for future experimental validation.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.132.suppl_3.18931
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1466401-X
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  • 2
    Online Resource
    Online Resource
    Abstract EP02: Identification Of Genetic Signals For “Diabesity” --- Type 2 Diabetes And Obesity -- Among African American And European American Participants In Four Cohorts Of The TOPMed Consortium
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 145, No. Suppl_1 ( 2022-03)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 145, No. Suppl_1 ( 2022-03)
    Abstract: Background: Diabesity defines the concurrent manifestation of type 2 diabetes (T2D) and obesity (BMI≥30 kg/m 2 ) in the development of cardiovascular diseases, although the genetic basis for this joint phenotype remain poorly understood. Objective: This study aimed to identify the overlapping genetic patterns for diabesity incidence in 3,231 self-reported African American (AA) and 8,252 European Americans (EA) participated in four cohorts of the Trans-Omics for Precision Medicine (TOPMed) consortium. Methods: Using marker set enrichment analysis (MSEA) of whole genome sequencing data, specific gene sets (pathways) and key driver (KD) genes (important hub genes overrepresented in a network of pathways) were identified for diabesity incidence. Using multi-tissue and multi-species gene expression signatures as molecular indicators of drug functions, their potential drug signatures were also examined. Results: Testing genome-wide significance (P-value 〈 10 -8 ) identified seven independent loci, six of which were replicated in the T2D Knowledge Portal (https://t2d.hugeamp.org/ )( NPFFR1, TRIO, G6PD, BCL11A, IGF1, and TCF7L2, P 〈 0.05) for diabetes and/or such obesity-related traits as blood pressure, lipids, glucose and insulin levels. One novel variant for diabesity, rs144540309, is an intronic region of GPAT3 (G 〉 A, AA MAF = 0.004, beta=3.66 and P=1.00e-8) whose enzyme plays important roles in dietary lipid absorption, enteric and hepatic lipid homeostasis, and entero-endocrine hormone production, along with 12 KEGG/Reactome/Biocarta pathways enriched for diabesity in AAs and 11 for EAs. In AAs, the top three pathways (ranked by P-value and false discovery rate [FDR]) were mitotic spindle checkpoint, resolution of sister chromatid cohesion, and rho GTPases activate formins, along with six KD genes ( NCKAP1L, CDCA8 , BUB1 , IRF5 , FYB , and C15orf23 ); in EAs, colorectal cancer, prostate cancer, and beta Catenin independent WNT signaling were the top 3 pathways (FDR≤0.25) including LEF1 . Top repositioned drugs derived from diabesity-related gene sets (FDR≤0.25) included Benzbromarone, Fenofibrate, Interleukin-1β, and antihypertensive. Conclusion: Our study supports the notion that both pathway and network-based analytical approaches may identify novel signals from gene sets for highly clustering clinical phenotypes such as diabetes and obesity and improve their target validation for intervention.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.145.suppl_1.EP02
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 3
    Online Resource
    Online Resource
    Famine and Trajectories of Body Mass Index, Waist Circumference, and Blood Pressure in Two Generations: Results From the CHNS From 1993–2015
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Hypertension Vol. 79, No. 3 ( 2022-03), p. 518-531
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. 3 ( 2022-03), p. 518-531
    Abstract: Early-life exposures play key roles in the development of metabolic diseases. Whether such effects exist beyond one generation remains unclear. This study aimed to determine the transgenerational association of early-life exposure to the Chinese famine of 1959 to 1962 with the trajectories of body mass index (BMI), waist circumference (WC), and blood pressure (BP) in 2 consecutive generations. Methods: We included 21 106 F1 observations born between 1954 and 1967 (median age: 45 years) and 1926 F2 observations (median age: 23 years) from the longitudinal household-based China Health and Nutrition Survey from 1993 to 2015. Trajectories of BMI, WC, systolic BP, and diastolic BP were fitted and compared between groups using linear mixed effect models. Results: Early-life exposure to famine was associated with increased BMI, WC, and BP in 2 consecutive generations with sex and age disparities. In F1, famine was associated with increased BMI, WC, systolic BP, and diastolic BP, especially in men or those aged older than 50 years ( P ranged from 〈 0.001 to 0.02). In F2 men but not women, the parental exposure to famine was associated with 0.59 kg/m 2 ([95% CI, 0.10–1.08], P =0.02) increase in BMI. In F2 aged ≥25 years but not those younger ones, the parental exposure to famine was associated with increased BMI (0.83 kg/m 2 [0.14–1.51], P =0.03), systolic BP (2.04 mm Hg [0.20–3.88], P =0.03), and diastolic BP (1.73 mm Hg [0.28–3.18], P =0.02). Conclusions: The effects of an adverse developmental environment through famine in early life on BMI and BP later in life may persist beyond one generation.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.121.18022
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2094210-2
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  • 4
    Online Resource
    Online Resource
    Genetic Determinants for Leisure-Time Physical Activity
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Medicine & Science in Sports & Exercise Vol. 50, No. 8 ( 2018-8), p. 1620-1628
    Details
    In: Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 8 ( 2018-8), p. 1620-1628
    Type of Medium: Online Resource
    ISSN: 1530-0315 , 0195-9131
    URL: Article
    DOI: 10.1249/MSS.0000000000001607
    RVK:
    ZX 1000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2031167-9
    SSG: 31
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