Browsing by Author "Graff, Mariaelisa"

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    Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents
    (2022) Kim, Daeeun; Justice, Anne E.; Chittoor, Geetha; Blanco, Estela; Burrows, Raquel; Graff, Mariaelisa; Green Howard, Annie; Wang, Yujie; Rohde, Rebecca; Buchanan, Victoria L.; Voruganti, V. Saroja; Almeida, Marcio; Peralta, Juan; Lehman, Donna M.; Curran, Joanne E.; Comuzzie, Anthony G.; Duggirala, Ravindranath; Blangero, John; Albala, Cecilia; Santos Martín, José Luis; Angel, Bárbara; Lozoff, Betsy; Gahagan, Sheila; North, Kari E.
    Background: Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers—adiponectin, leptin, ghrelin, and orexin—and their associations with CMD risk factors. Methods: We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling. Results: We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels. Conclusions: The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers.
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    Genome-wide association study identifying novel variant for fasting insulin and allelic heterogeneity in known glycemic loci in Chilean adolescents: The Santiago Longitudinal Study
    (2020) Buchanan, Victoria L.; Wang, Yujie; Blanco, Estela; Graff, Mariaelisa; Albala, Cecilia; Burrows, Raquel; Santos Martín, José Luis; Angel, Bárbara; Lozoff, Betsy; Saroja Voruganti, Venkata; Guo, Xiuqing; taylor, Kent D.; Chen, Yii-Der Ida; Yao, Jie; Tan, Jingyi; Downie, Carolina; Highland, Heather M.; Justice, Anne E.; Gahagan, Sheila; North, Kari E.
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    Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits
    (Springer Science and Business Media B.V., 2025) Petty, Lauren E.; Chen, Hung-Hsin; Frankel, Elizabeth G.; Zhu, Wanying; Downie, Carolina G.; Graff, Mariaelisa; Lin, Phillip; Sharma, Priya; Zhang, Xinruo; Scartozzi, Alyssa C.; Roshani, Rashedeh; Landman, Joshua M.; Boehnke, Michael; Bowden, Donald W.; Chambers, John C.; Mahajan, Anubha; McCarthy, Mark I.; Ng, Maggie C. Y.; Sim, Xueling; Spracklen, Cassandra N.; Zhang, Weihua; Preuss, Michael; Bottinger, Erwin P.; Nadkarni, Girish N.; Loos, Ruth J. F.; Chen, Yii-Der Ida; Tan, Jingyi; Ipp, Eli; Genter, Pauline; Emery, Leslie S.; Louie, Tin; Sofer, Tamar; Stilp, Adrienne M.; Taylor, Kent D.; Xiang, Anny H.; Buchanan, Thomas A.; Roll, Kathryn; Gao, Chuan; Palmer, Nicholette D.; Norris, Jill M.; Wagenknecht, Lynne E.; Nousome, Darryl; Varma, Rohit; McKean-Cowdin, Roberta; Guo, Xiuqing; Hai, Yang; Hsueh, Willa; Sandow, Kevin; Parra, Esteban J.; Cruz, Miguel; Valladares-Salgado, Adan; Wacher-Rodarte, Niels; Rotter, Jerome I.; Goodarzi, Mark O.; Rich, Stephen S.; Bertoni, Alain; Raffel, Leslie J.; Nadler, Jerry L.; Kandeel, Fouad R.; Duggirala, Ravindranath; Blangero, John; Lehman, Donna M.; DeFronzo, Ralph A.; Thameem, Farook; Wang, Yujie; Gahagan, Sheila; Blanco, Estela; Burrows, Raquel; Huerta-Chagoya, Alicia; Florez, Jose C.; Tusie-Luna, Teresa; Gonzalez-Villalpando, Clicerio; Orozco, Lorena; Haiman, Christopher A.; Hanis, Craig L.; Rohde, Rebecca; Whitsel, Eric A.; Reiner, Alexander P.; Kooperberg, Charles; Li, Yun; Duan, Qing; Lee, Miryoung; Correa-Burrows, Paulina; Fried, Susan K.; North, Kari E.; McCormick, Joseph B.; Fisher-Hoch, Susan P.; Gamazon, Eric R.; Morris, Andrew P.; Mercader, Josep M.; Highland, Heather M.; Below, Jennifer E.
    Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with transcriptomic and proteomic measure using multi-omics data from a Hispanic/Latino population. Using this approach, we identify genes linked to type 2 diabetes and lipid/lipoprotein traits, including TMEM205 and NEDD9 for HDL cholesterol, TREH for triglycerides, and ANXA4 for type 2 diabetes.