Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents. Kim, D., Justice, A. E, Chittoor, G., Blanco, E., Burrows, R., Graff, M., Howard, A. G., Wang, Y., Rohde, R., Buchanan, V. L, Voruganti, V S., Almeida, M., Peralta, J., Lehman, D. M, Curran, J. E, Comuzzie, A. G, Duggirala, R., Blangero, J., Albala, C., Santos, J. L, Angel, B., Lozoff, B., Gahagan, S., & North, K. E Pediatric Research, 92(2):563–571, Springer Science and Business Media LLC, August, 2022.
Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents [link]Paper  doi  abstract   bibtex   
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. IMPACT: This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.
@ARTICLE{Kim2022-in,
  title     = "Genetic determinants of metabolic biomarkers and their
               associations with cardiometabolic traits in {Hispanic/Latino}
               adolescents",
  author    = "Kim, Daeeun and Justice, Anne E and Chittoor, Geetha and Blanco,
               Estela and Burrows, Raquel and Graff, Mariaelisa and Howard,
               Annie Green and Wang, Yujie and Rohde, Rebecca and Buchanan,
               Victoria L and Voruganti, V Saroja and Almeida, Marcio and
               Peralta, Juan and Lehman, Donna M and Curran, Joanne E and
               Comuzzie, Anthony G and Duggirala, Ravindranath and Blangero,
               John and Albala, Cecilia and Santos, Jos{\'e} L and Angel,
               B{\'a}rbara and Lozoff, Betsy and Gahagan, Sheila and North,
               Kari E",
  abstract  = "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. IMPACT: This study characterized the genetic
               underpinnings of four metabolic hormones and investigated their
               potential influence on adiposity and insulin biology among
               Hispanic/Latino adolescents. Fasting blood insulin and insulin
               resistance were associated with polygenic risk score (PRS) for
               adiponectin, leptin, and ghrelin, with evidence of some degree
               of mediation by the biomarker levels. Body fat percent (BF\%)
               was also associated with PRS for adiponectin and leptin. This
               provides important insight on biological mechanisms underlying
               early metabolic dysfunction and reveals candidates for
               prevention efforts. Our findings also highlight the importance
               of ancestrally diverse populations to facilitate valid studies
               of the genetic architecture of metabolic biomarker levels.",
  journal   = "Pediatric Research",
  publisher = "Springer Science and Business Media LLC",
  volume    =  92,
  number    =  2,
  pages     = "563--571",
  month     =  aug,
  year      =  2022,
  language  = "en",
	pmid = {34645953},
	url = {https://pubmed.ncbi.nlm.nih.gov/34645953/},
  bdsk-url-1 = {https://doi.org/10.1038/s41390-021-01729-7},
  doi = {10.1038/s41390-021-01729-7}
}

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