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. Paper abstract bibtex 4 downloads 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}
}
Downloads: 4
{"_id":"uEsTyamg5R9w7dxT8","bibbaseid":"kim-justice-chittoor-blanco-burrows-graff-howard-wang-etal-geneticdeterminantsofmetabolicbiomarkersandtheirassociationswithcardiometabolictraitsinhispaniclatinoadolescents-2022","author_short":["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"],"bibdata":{"bibtype":"article","type":"article","title":"Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents","author":[{"propositions":[],"lastnames":["Kim"],"firstnames":["Daeeun"],"suffixes":[]},{"propositions":[],"lastnames":["Justice"],"firstnames":["Anne","E"],"suffixes":[]},{"propositions":[],"lastnames":["Chittoor"],"firstnames":["Geetha"],"suffixes":[]},{"propositions":[],"lastnames":["Blanco"],"firstnames":["Estela"],"suffixes":[]},{"propositions":[],"lastnames":["Burrows"],"firstnames":["Raquel"],"suffixes":[]},{"propositions":[],"lastnames":["Graff"],"firstnames":["Mariaelisa"],"suffixes":[]},{"propositions":[],"lastnames":["Howard"],"firstnames":["Annie","Green"],"suffixes":[]},{"propositions":[],"lastnames":["Wang"],"firstnames":["Yujie"],"suffixes":[]},{"propositions":[],"lastnames":["Rohde"],"firstnames":["Rebecca"],"suffixes":[]},{"propositions":[],"lastnames":["Buchanan"],"firstnames":["Victoria","L"],"suffixes":[]},{"propositions":[],"lastnames":["Voruganti"],"firstnames":["V","Saroja"],"suffixes":[]},{"propositions":[],"lastnames":["Almeida"],"firstnames":["Marcio"],"suffixes":[]},{"propositions":[],"lastnames":["Peralta"],"firstnames":["Juan"],"suffixes":[]},{"propositions":[],"lastnames":["Lehman"],"firstnames":["Donna","M"],"suffixes":[]},{"propositions":[],"lastnames":["Curran"],"firstnames":["Joanne","E"],"suffixes":[]},{"propositions":[],"lastnames":["Comuzzie"],"firstnames":["Anthony","G"],"suffixes":[]},{"propositions":[],"lastnames":["Duggirala"],"firstnames":["Ravindranath"],"suffixes":[]},{"propositions":[],"lastnames":["Blangero"],"firstnames":["John"],"suffixes":[]},{"propositions":[],"lastnames":["Albala"],"firstnames":["Cecilia"],"suffixes":[]},{"propositions":[],"lastnames":["Santos"],"firstnames":["José","L"],"suffixes":[]},{"propositions":[],"lastnames":["Angel"],"firstnames":["Bárbara"],"suffixes":[]},{"propositions":[],"lastnames":["Lozoff"],"firstnames":["Betsy"],"suffixes":[]},{"propositions":[],"lastnames":["Gahagan"],"firstnames":["Sheila"],"suffixes":[]},{"propositions":[],"lastnames":["North"],"firstnames":["Kari","E"],"suffixes":[]}],"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":"August","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","bibtex":"@ARTICLE{Kim2022-in,\n title = \"Genetic determinants of metabolic biomarkers and their\n associations with cardiometabolic traits in {Hispanic/Latino}\n adolescents\",\n author = \"Kim, Daeeun and Justice, Anne E and Chittoor, Geetha and Blanco,\n Estela and Burrows, Raquel and Graff, Mariaelisa and Howard,\n Annie Green and Wang, Yujie and Rohde, Rebecca and Buchanan,\n Victoria L and Voruganti, V Saroja and Almeida, Marcio and\n Peralta, Juan and Lehman, Donna M and Curran, Joanne E and\n Comuzzie, Anthony G and Duggirala, Ravindranath and Blangero,\n John and Albala, Cecilia and Santos, Jos{\\'e} L and Angel,\n B{\\'a}rbara and Lozoff, Betsy and Gahagan, Sheila and North,\n Kari E\",\n abstract = \"BACKGROUND: Metabolic regulation plays a significant role in\n energy homeostasis, and adolescence is a crucial life stage for\n the development of cardiometabolic disease (CMD). This study\n aims to investigate the genetic determinants of metabolic\n biomarkers-adiponectin, leptin, ghrelin, and orexin-and their\n associations with CMD risk factors. METHODS: We characterized\n the genetic determinants of the biomarkers among Hispanic/Latino\n adolescents of the Santiago Longitudinal Study (SLS) and\n identified the cumulative effects of genetic variants on\n adiponectin and leptin using biomarker polygenic risk scores\n (PRS). We further investigated the direct and indirect effect of\n the biomarker PRS on downstream body fat percent (BF\\%) and\n glycemic traits using structural equation modeling. RESULTS: We\n identified putatively novel genetic variants associated with the\n metabolic biomarkers. A substantial amount of biomarker variance\n was explained by SLS-specific PRS, and the prediction was\n improved by including the putatively novel loci. Fasting blood\n insulin and insulin resistance were associated with PRS for\n adiponectin, leptin, and ghrelin, and BF\\% was associated with\n PRS for adiponectin and leptin. We found evidence of substantial\n mediation of these associations by the biomarker levels.\n CONCLUSIONS: The genetic underpinnings of metabolic biomarkers\n can affect the early development of CMD, partly mediated by the\n biomarkers. IMPACT: This study characterized the genetic\n underpinnings of four metabolic hormones and investigated their\n potential influence on adiposity and insulin biology among\n Hispanic/Latino adolescents. Fasting blood insulin and insulin\n resistance were associated with polygenic risk score (PRS) for\n adiponectin, leptin, and ghrelin, with evidence of some degree\n of mediation by the biomarker levels. Body fat percent (BF\\%)\n was also associated with PRS for adiponectin and leptin. This\n provides important insight on biological mechanisms underlying\n early metabolic dysfunction and reveals candidates for\n prevention efforts. Our findings also highlight the importance\n of ancestrally diverse populations to facilitate valid studies\n of the genetic architecture of metabolic biomarker levels.\",\n journal = \"Pediatric Research\",\n publisher = \"Springer Science and Business Media LLC\",\n volume = 92,\n number = 2,\n pages = \"563--571\",\n month = aug,\n year = 2022,\n language = \"en\",\n pmid = {34645953},\n\turl = {https://pubmed.ncbi.nlm.nih.gov/34645953/},\n bdsk-url-1 = {https://doi.org/10.1038/s41390-021-01729-7}\n}\n\n\n\n","author_short":["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. 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