48 results on '"Hanson, Robert L."'
Search Results
2. DNA methylation markers for kidney function and progression of diabetic kidney disease
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Li, Kelly Yichen, Tam, Claudia Ha Ting, Liu, Hongbo, Day, Samantha, Lim, Cadmon King Poo, So, Wing Yee, Huang, Chuiguo, Jiang, Guozhi, Shi, Mai, Lee, Heung Man, Lan, Hui-yao, Szeto, Cheuk-Chun, Hanson, Robert L., Nelson, Robert G., Susztak, Katalin, Chan, Juliana C. N., Yip, Kevin Y., and Ma, Ronald C. W.
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- 2023
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3. Identification and characterization of the long non-coding RNA NFIA-AS2 as a novel locus for body mass index in American Indians
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Bandesh, Khushdeep, Traurig, Michael, Chen, Peng, Hsueh, Wen-Chi, Hanson, Robert L., Piaggi, Paolo, and Baier, Leslie J.
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- 2023
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4. The utility of a type 2 diabetes polygenic score in addition to clinical variables for prediction of type 2 diabetes incidence in birth, youth and adult cohorts in an Indigenous study population
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Wedekind, Lauren E., Mahajan, Anubha, Hsueh, Wen-Chi, Chen, Peng, Olaiya, Muideen T., Kobes, Sayuko, Sinha, Madhumita, Baier, Leslie J., Knowler, William C., McCarthy, Mark I., and Hanson, Robert L.
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- 2023
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5. Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS)
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Sandforth, Arvid, von Schwartzenberg, Reiner Jumpertz, Arreola, Elsa Vazquez, Hanson, Robert L, Sancar, Gencer, Katzenstein, Sarah, Lange, Karl, Preißl, Hubert, Dreher, Simon I, Weigert, Cora, Wagner, Robert, Kantartzis, Kostantinos, Machann, Jürgen, Schick, Fritz, Lehmann, Rainer, Peter, Andreas, Katsouli, Nikoletta, Ntziachristos, Vasilis, Dannecker, Corinna, Fritsche, Louise, Perakakis, Nikolaos, Heni, Martin, Nawroth, Peter Paul, Kopf, Stefan, Pfeiffer, Andreas F H, Kabisch, Stefan, Stumvoll, Michael, Schwarz, Peter E H, Hauner, Hans, Lechner, Andreas, Seissler, Jochen, Yurchenko, Iryna, Icks, Andrea, Solimena, Michele, Häring, Hans-Ulrich, Szendroedi, Julia, Schürmann, Annette, de Angelis, Martin Hrabé, Blüher, Matthias, Roden, Michael, Bornstein, Stefan R, Stefan, Norbert, Fritsche, Andreas, and Birkenfeld, Andreas L
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- 2023
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6. Diagnostic criteria and etiopathogenesis of type 2 diabetes and its complications: Lessons from the Pima Indians
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Looker, Helen C, Chang, Douglas C, Baier, Leslie J, Hanson, Robert L, and Nelson, Robert G
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- 2023
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7. Functional characterization of a novel p.Ser76Thr variant in IGFBP4 that associates with body mass index in American Indians
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Muller, Yunhua L., Saporito, Michael, Day, Samantha, Bandesh, Khushdeep, Koroglu, Cigdem, Kobes, Sayuko, Knowler, William C., Hanson, Robert L., Van Hout, Cristopher V., Shuldiner, Alan R., Bogardus, Clifton, and Baier, Leslie J.
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- 2022
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8. An E115A missense variant in CERS2 is associated with increased sleeping energy expenditure and hepatic insulin resistance in American Indians
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Heinitz, Sascha, primary, Traurig, Michael, additional, Krakoff, Jonathan, additional, Rabe, Philipp, additional, Stäubert, Claudia, additional, Kobes, Sayuko, additional, Hanson, Robert L., additional, Stumvoll, Michael, additional, Blüher, Matthias, additional, Bogardus, Clifton, additional, Baier, Leslie, additional, and Piaggi, Paolo, additional
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- 2024
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9. Association of protein function-altering variants with cardiometabolic traits: the strong heart study
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Shan, Yue, Cole, Shelley A., Haack, Karin, Melton, Phillip E., Best, Lyle G., Bizon, Christopher, Kobes, Sayuko, Köroğlu, Çiğdem, Baier, Leslie J., Hanson, Robert L., Sanna, Serena, Li, Yun, and Franceschini, Nora
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- 2022
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10. Study protocol for Early Tracking of Childhood Health determinants (ETCHED): A longitudinal observational life course study.
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Arreola, Elsa Vazquez, Coonrod, Dean V., Roy Choudhury, Sourav, Knowler, William C., Hoskin, Mary, Wasak, Dorota, Williams, Rachel, Hanson, Robert L., Pack, Elena, Caballero, Rachel, Gonzalez, Amanda, and Sinha, Madhumita
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PREGNANT women ,FAMILY structure ,MINORITY youth ,HEALTH of minorities ,CHILDHOOD obesity - Abstract
Background: The prevalence of childhood obesity and diabetes continues to rise in the United States (US), especially among minority populations. The objective of the Early Tracking of Childhood Health Determinants (ETCHED) study is to investigate the role of adverse fetal and early-life risk exposures that contribute to the development of childhood obesity and metabolic risk. Methods: ETCHED is a longitudinal observational study of American Indian/Alaska Native (AI/AN) and Hispanic pregnant woman and their offspring. Pregnant mothers ≥ 18 years old are enrolled at a large public hospital system in the southwestern US. Enrolled mothers are followed through pregnancy, delivery, and the maternal/offspring dyad will be followed until the child's 18th birthday. At each maternal visit, questionnaires assessing medical history, diet, physical activity, sleep, perceived stress, and socioeconomic and sociocultural information are obtained. Standard laboratory tests during maternal visits include glycemic measures, lipids, and renal function. Additional bio samples obtained include venous blood samples and cord blood for obesity/metabolic biomarkers and genetic/epigenetic testing, urinalysis, placental tissue for examining functional pathways, breast milk for metabolomics, and stool for metabolites and microbiome analysis. The offspring will have 6 infant/toddler visits at 6–12 weeks, 4 months, 6 months, 18 months, 2 and 3 years respectively. Thereafter, they will undergo comprehensive research visits (major visits) at 4–5 years, 6–9 years, 10–13 years, and 14–17 years. The major visits in children include detailed medical history, anthropometry, developmental assessment, socioeconomic and environmental assessments (food insecurity, family structure, and childcare), feeding and activity, biochemical tests, genetics/epigenetic testing, and ultrasound elastography. Electronic health records will be reviewed for additional clinical information. The primary analysis will constitute estimation of correlation coefficients between continuous variables. The planned study duration in this ongoing study is 23-years. Discussion: This is a life course study that that will examine biological and environmental risk factors for obesity and cardiometabolic risk from the intrauterine period to early childhood and adolescence in a population with high-risk of obesity and type 2 diabetes in the United States. The ETCHED study would also provide a unique opportunity to combine multi-omics and clinical data to create novel integrative models to predict the cardiometabolic risk associated with childhood obesity and possibly identify etiopathogenetic mechanisms and future targets of intervention. Trial registration number: ClinicalTrials.gov identifier: NCT03481829. Updated July 19, 2024, https://clinicaltrials.gov/study/NCT03481829?cond=ETCHED&rank=1. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Identification and functional validation of rare coding variants in genes linked to monogenic obesity.
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Köroğlu, Çiğdem, Traurig, Michael, Muller, Yunhua L., Day, Samantha E., Piaggi, Paolo, Wiedrich, Kim, Vazquez, Laura, Hanson, Robert L., Van Hout, Cristopher V., Alkelai, Anna, Shuldiner, Alan R., Bogardus, Clifton, and Baier, Leslie J.
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MISSENSE mutation ,GENETIC variation ,FUNCTIONAL analysis ,OBESITY ,ADULTS - Abstract
Objective: Rare cases of monogenic obesity, which may respond to specific therapeutics, can remain undetected in populations in which polygenic obesity is prevalent. This study examined rare DNA variation in established monogenic obesity genes within a community using whole‐exome sequence data from 6803 longitudinally studied individuals. Methods: Exome data across 15 monogenic obesity genes were analyzed for nonsynonymous variants observed in any child with a maximum BMI z score > 2 (N = 279) but not observed in a child with a maximum BMI z score ≤ 0 (n = 1542) or that occurred in adults in the top 5th percentile of BMI (n = 263) but not in adults below the median BMI (n = 2629). Variants were then functionally analyzed using luciferase assays. Results: The comparisons between cases of obesity and controls identified eight missense variants in six genes: DYRK1B, KSR2, MC4R, NTRK2, PCSK1, and SIM1. Among these, MC4R p.A303P and p.R165G were previously shown to impair MC4R function. Functional analyses of the remaining six variants suggest that KSR2 p.I402F and p.T193I and NTRK2 p.S249Y alter protein function. Conclusions: In addition to MC4R, rare missense variants in KSR2 and NTRK2 may potentially explain the severe obesity observed for the carriers. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Epistasis Between HLA-DRB1*16:02:01 and SLC16A11 T-C-G-T-T Reduces Odds for Type 2 Diabetes in Southwest American Indians
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Williams, Robert C., primary, Hanson, Robert L., additional, Peters, Bjoern, additional, Kearns, Kendall, additional, Knowler, William C., additional, Bogardus, Clifton, additional, and Baier, Leslie J., additional
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- 2024
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13. Role of Weight Loss Induced Prediabetes Remission in the Prevention of Type 2 Diabetes - Time to Improve Diabetes Prevention
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von Schwartzenberg, Reiner Jumpertz, primary, Arreola, Elsa Vazquez, additional, Sandforth, Arvid, additional, Hanson, Robert L., additional, and Birkenfeld, Andreas L., additional
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- 2024
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14. Novel signals and polygenic score for height are associated with pubertal growth traits in Southwestern American Indians
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Ramírez-Luzuriaga, Maria J, primary, Kobes, Sayuko, additional, Hsueh, Wen-Chi, additional, Baier, Leslie J, additional, and Hanson, Robert L, additional
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- 2024
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15. Insulin resistance before type 2 diabetes onset is associated with increased risk of albuminuria after diabetes onset: A prospective cohort study
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Willig, Meeah R., primary, Stinson, Emma J., additional, Looker, Helen C., additional, Piaggi, Paolo, additional, Mitchell, Cassie M., additional, Hanson, Robert L., additional, Nelson, Robert G., additional, Krakoff, Jonathan, additional, and Chang, Douglas C., additional
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- 2024
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16. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
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Bradfield, Jonathan P., Kember, Rachel L., Ulrich, Anna, Balkiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M., Bell, Joshua A., Broadaway, K. Alaine, Chen, Zhanghua, Chai, Jin Fang, Davies, Neil M., Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M., Have, Christian Theil, Strachan, David P., Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H., Wang, Carol A., Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W. James, Glessner, Joseph T., Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L., Guxens, Mònica, Felix, Janine F., Hansen, Torben, Jaddoe, Vincent W.V., Perry, John R.B., Rivadeneira, Fernando, Bradfield, Jonathan P., Kember, Rachel L., Ulrich, Anna, Balkiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M., Bell, Joshua A., Broadaway, K. Alaine, Chen, Zhanghua, Chai, Jin Fang, Davies, Neil M., Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M., Have, Christian Theil, Strachan, David P., Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H., Wang, Carol A., Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W. James, Glessner, Joseph T., Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L., Guxens, Mònica, Felix, Janine F., Hansen, Torben, Jaddoe, Vincent W.V., Perry, John R.B., and Rivadeneira, Fernando
- Abstract
BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.
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- 2024
17. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes
- Author
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Bradfield, Jonathan P, Kember, Rachel L, Ulrich, Anna, Balkiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M, Bell, Joshua A, Broadaway, K Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M, Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M, Have, Christian Theil, Strachan, David P, Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H, Wang, Carol A, Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W James, Glessner, Joseph T, Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L, Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Hansen, Torben, Holm, Jens-Christian, Sørensen, Thorkild I A, Grant, Struan F A, Cousminer, Diana L, Bradfield, Jonathan P, Kember, Rachel L, Ulrich, Anna, Balkiyarova, Zhanna, Alyass, Akram, Aris, Izzuddin M, Bell, Joshua A, Broadaway, K Alaine, Chen, Zhanghua, Chai, Jin-Fang, Davies, Neil M, Fernandez-Orth, Dietmar, Bustamante, Mariona, Fore, Ruby, Ganguli, Amitavo, Heiskala, Anni, Hottenga, Jouke-Jan, Íñiguez, Carmen, Kobes, Sayuko, Leinonen, Jaakko, Lowry, Estelle, Lyytikainen, Leo-Pekka, Mahajan, Anubha, Pitkänen, Niina, Schnurr, Theresia M, Have, Christian Theil, Strachan, David P, Thiering, Elisabeth, Vogelezang, Suzanne, Wade, Kaitlin H, Wang, Carol A, Wong, Andrew, Holm, Louise Aas, Chesi, Alessandra, Choong, Catherine, Cruz, Miguel, Elliott, Paul, Franks, Steve, Frithioff-Bøjsøe, Christine, Gauderman, W James, Glessner, Joseph T, Gilsanz, Vicente, Griesman, Kendra, Hanson, Robert L, Kaakinen, Marika, Kalkwarf, Heidi, Kelly, Andrea, Hansen, Torben, Holm, Jens-Christian, Sørensen, Thorkild I A, Grant, Struan F A, and Cousminer, Diana L
- Abstract
Background: Pubertal growth patterns correlate with future health outcomes. How‑ever, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Transla‑tion And Rotation (SITAR) growth curve analysis on~56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analy‑ses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Results: Large-scale growth modeling enables an unprecedented view of adoles‑ cent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide signifcant loci and leverage trans-ancestry data to perform fnemapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with diferent growth trajectories correlated with dif‑ferent outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fbrillation. Conclusion: We report novel genetic associations with the tempo of pubertal growth and fnd that genetic determinants of growth are correlated with reproductive, glyce‑mic, respiratory, and cardiac traits in adulthood. These results aid in identifying specifc growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern., BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank.RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation.CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.
- Published
- 2024
18. Effects of theABCC8R1420H loss-of-function variant on beta-cell function, diabetes incidence, and retinopathy
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Vazquez Arreola, Elsa, primary, Knowler, William C, additional, Baier, Leslie J, additional, and Hanson, Robert L, additional
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- 2023
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19. Further evidence supporting a potential role for ADH1B in obesity
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Morales, Liza D., Cromack, Douglas T., Tripathy, Devjit, Fourcaudot, Marcel, Kumar, Satish, Curran, Joanne E., Carless, Melanie, Göring, Harald H. H., Hu, Shirley L., Lopez-Alvarenga, Juan Carlos, Garske, Kristina M., Pajukanta, Päivi, Small, Kerrin S., Glastonbury, Craig A., Das, Swapan K., Langefeld, Carl, Hanson, Robert L., Hsueh, Wen-Chi, Norton, Luke, Arya, Rector, Mummidi, Srinivas, Blangero, John, DeFronzo, Ralph A., Duggirala, Ravindranath, and Jenkinson, Christopher P.
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- 2021
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20. Epidemiology of Type 2 Diabetes in Indigenous Communities in the United States
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Wedekind, Lauren E., Mitchell, Cassie M., Andersen, Coley C., Knowler, William C., and Hanson, Robert L.
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- 2021
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21. Glycemic Measures in Childhood as Predictors of Future Diabetes-Related Microvascular Complications in an Indigenous American Population
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Vazquez, Laura, primary, Vazquez Arreola, Elsa, additional, Hanson, Robert L., additional, and Sinha, Madhumita, additional
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- 2023
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22. The Effect of Interventions to Prevent Type 2 Diabetes on the Development of Diabetic Retinopathy: The DPP/DPPOS Experience
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White, Neil H., Pan, Qing, Knowler, William C., Schroeder, Emily B., Dabelea, Dana, Chew, Emily Y., Blodi, Barbara, Goldberg, Ronald B., Pi-Sunyer, Xavier, Darwin, Christine, Schlögl, Mathias, Nathan, David M., Goldstein, Barry J., Furlong, Kevin, Smith, Kellie A., Mendoza, Jewel, Wildman, Wendi, Simmons, Marsha, Jensen, Genine, Liberoni, Renee, Spandorfer, John, Pepe, Constance, Donahue, Richard P., Prineas, Ronald, Rowe, Patricia, Giannella, Anna, Calles, Jeanette, Sanguily, Juliet, Cassanova-Romero, Paul, Castillo-Florez, Sumaya, Florez, Hermes J., Garg, Rajesh, Kirby, Lascelles, Lara, Olga, Larreal, Carmen, McLymont, Valerie, Mendez, Jadell, Perry, Arlette, Saab, Patrice, Veciana, Bertha, Haffner, Steven M., Hazuda, Helen P., Montez, Maria G., Isaac, Juan, Hattaway, Kathy, Lorenzo, Carlos, Martinez, Arlene, Salazar, Monica, Walker, Tatiana, Hamman, Richard F., Nash, Patricia V., Steinke, Sheila C., Testaverde, Lisa, Truong, Jennifer, Anderson, Denise R., Ballonoff, Larry B., Bouffard, Alexis, Boxer, Rebecca S., Bucca, Brian, Calonge, B. Ned, Delve, Lynne, Farago, Martha, Hill, James O., Hoyer, Shelley R., Jenkins, Tonya, Jortberg, Bonnie T., Lenz, Dione, Miller, Marsha, Nilan, Thomas, Perreault, Leigh, Price, David W., Regensteiner, Judith G., Seagle, Helen, Smith, Carissa M., VanDorsten, Brent, Horton, Edward S., Munshi, Medha, Lawton, Kathleen E., Poirier, Catherine S., Swift, Kati, Jackson, Sharon D., Arky, Ronald A., Bryant, Marybeth, Burke, Jacqueline P., Caballero, Enrique, Callaphan, Karen M., Fargnoli, Barbara, Franklin, Therese, Ganda, Om P., Guidi, Ashley, Guido, Mathew, Jacobsen, Alan M., Kula, Lyn M., Kocal, Margaret, Lambert, Lori, Ledbury, Sarah, Malloy, Maureen A., Middelbeek, Roeland J.W., Nicosia, Maryanne, Oldmixon, Cathryn F., Pan, Jocelyn, Quitingon, Marizel, Rainville, Riley, Rubtchinsky, Stacy, Seely, Ellen W., Sansoucy, Jessica, Schweizer, Dana, Simonson, Donald, Smith, Fannie, Solomon, Caren G., Spellman, Jeanne, Warram, James, Kahn, Steven E., Montgomery, Brenda K., Fattaleh, Basma, Colegrove, Celeste, Fujimoto, Wilfred, Knopp, Robert H., Lipkin, Edward W., Marr, Michelle, Morgan-Taggart, Ivy, Murillo, Anne, O’Neal, Kayla, Trence, Dace, Taylor, Lonnese, Thomas, April, Tsai, Elaine C., Kitabchi, Abbas E., Dagogo-Jack, Samuel, Murphy, Mary E., Taylor, Laura, Dolgoff, Jennifer, Hampton, Ethel Faye, Applegate, William B., Bryer-Ash, Michael, Clark, Debra, Frieson, Sandra L., Ibebuogu, Uzoma, Imseis, Raed, Lambeth, Helen, Lichtermann, Lynne C., Oktaei, Hooman, Ricks, Harriet, Rutledge, Lily M.K., Sherman, Amy R., Smith, Clara M., Soberman, Judith E., Williamsleaves, Beverly, Patel, Avnisha, Nyenwe, Ebenezer A., Metzger, Boyd E., Molitch, Mark E., Wallia, Amisha, Johnson, Mariana K., VanderMolen, Sarah, Adelman, Daphne T., Behrends, Catherine, Cook, Michelle, Fitzgibbon, Marian, Giles, Mimi M., Hartmuller, Monica, Johnson, Cheryl K.H., Larsen, Diane, Lowe, Anne, Lyman, Megan, McPherson, David, Penn, Samsam C., Pitts, Thomas, Reinhart, Renee, Roston, Susan, Schinleber, Pamela A., McKitrick, Charles, Turgeon, Heather, Larkin, Mary, Mugford, Marielle, Thangthaeng, Nopporn, Leander, Fernelle, Abbott, Kathy, Anderson, Ellen, Bissett, Laurie, Bondi, Kristy, Cagliero, Enrico, Florez, Jose C., Delahanty, Linda, Goldman, Valerie, Grassa, Elaine, Gurry, Lindsey, D’Anna, Kali, Leandre, Fernelle, Lou, Peter, Poulos, Alexandra, Raymond, Elyse, Ripley, Valerie, Stevens, Christine, Tseng, Beverly, Olefsky, Jerrold M., Barrettonnor, Elizabeth, Mudaliar, Sunder, Rosario Araneta, Maria, Carrion-Petersen, Mary Lou, Vejvoda, Karen, Bassiouni, Sarah, Beltran, Madeline, Claravall, Lauren N., Dowden, Jonalle M., Edelman, Steven V., Garimella, Pranav, Henry, Robert R., Horne, Javiva, Lamkin, Marycie, Szerdi Janesch, Simona, Leos, Diana, Polonsky, William, Ruiz, Rosa, Smith, Jean, Torio-Hurley, Jennifer, Pi-Sunyer, F. Xavier, Laferrere, Blandine, Lee, Jane E., Hagamen, Susan, Kelly-Dinham, Kim, Allison, David B., Agharanya, Nnenna, Aronoff, Nancy J., Baldo, Maria, Crandall, Jill P., Foo, Sandra T., Luchsinger, Jose A., Pal, Carmen, Parkes, Kathy, Pena, Mary Beth, Roman, Julie, Rooney, Ellen S., VanWye, Gretchen E.H., Viscovich, Kristine A., Prince, Melvin J., Marrero, David G., Mather, Kieren J., De Groot, Mary, Kelly, Susie M., Jackson, Marcia A., McAtee, Gina, Putenney, Paula, Ackermann, Ronald T., Cantrell, Carolyn M., Dotson, Yolanda F., Fineberg, Edwin S., Fultz, Megan, Guare, John C., Hadden, Angela, Ignaut, James M., Kirkman, Marion S., O’Kelly Phillips, Erin, Pinner, Kisha L., Porter, Beverly D., Roach, Paris J., Rowland, Nancy D., Wheeler, Madelyn L., Ratner, Robert E., Aroda, Vanita, Magee, Michelle, Youssef, Gretchen, Shapiro, Sue, Andon, Natalie, Bavido-Arrage, Catherine, Boggs, Geraldine, Bronsord, Marjorie, Brown, Ernestine, Love Burkott, Holly, Cheatham, Wayman W., Cola, Susan, Evans, Cindy, Gibbs, Peggy, Kellum, Tracy, Leon, Lilia, Lagarda, Milvia, Levatan, Claresa, Lindsay, Milajurine, Nair, Asha K., Park, Jean, Passaro, Maureen, Silverman, Angela, Uwaifo, Gabriel, Wells-Thayer, Debra, Wiggins, Renee, Saad, Mohammed F., Watson, Karol, Budget, Maria, Jinagouda, Sujata, Botrous, Medhat, Sosa, Anthony, Tadros, Sameh, Akbar, Khan, Conzues, Claudia, Magpuri, Perpetua, Ngo, Kathy, Rassam, Amer, Waters, Debra, Xapthalamous, Kathy, Santiago, Julio V., Brown, Angela L., Santiago, Ana, Das, Samia, Khare-Ranade, Prajakta, Stich, Tamara, Fisher, Edwin, Hurt, Emma, Jones, Jackie, Jones, Tracy, Kerr, Michelle, McCowan, Sherri, Ryder, Lucy, Wernimont, Cormarie, Saudek, Christopher D., Hill Golden, Sherita, Bradley, Vanessa, Sullivan, Emily, Whittington, Tracy, Abbas, Caroline, Allen, Adrienne, Brancati, Frederick L., Cappelli, Sharon, Clark, Jeanne M., Charleston, Jeanne B., Freel, Janice, Horak, Katherine, Greene, Alicia, Jiggetts, Dawn, Johnson, Delois, Joseph, Hope, Kalyani, Rita, Loman, Kimberly, Mathioudakis, Nestoras, Maruthur, Nisa, Mosley, Henry, Reusing, John, Rubin, Richard R., Samuels, Alafia, Shields, Thomas, Stephens, Shawne, Stewart, Kerry J., Thomas, LeeLana, Utsey, Evonne, Williamson, Paula, Schade, David S., Adams, Karwyn S., Johannes, Carolyn, Hemphill, Claire, Hyde, Penny, Canady, Janene L., Atler, Leslie F., Boyle, Patrick J., Burge, Mark R., Chai, Lisa, Colleran, Kathleen, Fondino, Ateka, Gonzales, Ysela, Hernandez-McGinnis, Doris A., Katz, Patricia, King, Carolyn, Middendorf, Julia, Rubinchik, Sofya, Senter, Willette, Shamoon, Harry, Crandall, Jill, Brown, Janet O., Trandafirescu, Gilda, Powell, Danielle, Adorno, Elsie, Cox, Liane, Duffy, Helena, Engel, Samuel, Friedler, Allison, Goldstein, Angela, Howardentury, Crystal J., Lukin, Jennifer, Kloiber, Stacey, Longchamp, Nadege, Martinez, Helen, Pompi, Dorothy, Scheindlin, Jonathan, Tomuta, Norica, Violino, Elissa, Walker, Elizabeth A., Wylie-Rosett, Judith, Zimmerman, Elise, Zonszein, Joel, Wing, Rena R., Orchard, Trevor, Venditti, Elizabeth, Koenning, Gaye, Kramer, M. Kaye, Smith, Marie, Jeffries, Susan, Weinzierl, Valarie, Barr, Susan, Benchoff, Catherine, Boraz, Miriam, Clifford, Lisa, Culyba, Rebecca, Frazier, Marlene, Gilligan, Ryan, Guimond, Stephanie, Harrier, Susan, Harris, Louann, Kriska, Andrea, Manjoo, Qurashia, Mullen, Monica, Noel, Alicia, Otto, Amy, Pettigrew, Jessica, Rockette-Wagner, Bonny, Rubinstein, Debra, Semler, Linda, Smith, Cheryl F., Williams, Katherine V., Wilson, Tara, Arakaki, Richard F., Mau, Marjorie K., Latimer, Renee W., Isonaga, Mae K., Baker-Ladao, Narleen K., Bow, Ralph, Bermudez, Nina E., Dias, Lorna, Inouye, Jillian, Melish, John S., Mikami, Kathy, Mohideen, Pharis, Odom, Sharon K., Perry, Raynette U., Yamamoto, Robin E., Hanson, Robert L., Shah, Vallabh, Hoskin, Mary A., Percy, Carol A., Cooeyate, Norman, Natewa, Camille, Dodge, Charlotte, Enote, Alvera, Anderson, Harelda, Acton, Kelly J., Andre, Vickie L., Barber, Rosalyn, Begay, Shandiin, Bennett, Peter H., Benson, Mary Beth, Bird, Evelyn C., Broussard, Brenda A., Bucca, Brian C., Chavez, Marcella, Cook, Sherron, Curtis, Jeff, Dacawyma, Tara, Doughty, Matthew S., Duncan, Roberta, Edgerton, Cyndy, Ghahate, Jacqueline M., Glass, Justin, Glass, Martia, Gohdes, Dorothy, Grant, Wendy, Horse, Ellie, Ingraham, Louise E., Jackson, Merry, Jay, Priscilla, Kaskalla, Roylen S., Kavena, Karen, Kessler, David, Kobus, Kathleen M., Krakoff, Jonathan, Kurland, Jason, Manus, Catherine, McCabe, Cherie, Michaels, Sara, Morgan, Tina, Nashboo, Yolanda, Nelson, Julie A., Poirier, Steven, Polczynski, Evette, Piromalli, Christopher, Reidy, Mike, Roumain, Jeanine, Rowse, Debra, Roy, Robert J., Sangster, Sandra, Sewenemewa, Janet, Smart, Miranda, Spencer, Chelsea, Tonemah, Darryl, Williams, Rachel, Wilson, Charlton, Yazzie, Michelle, Bain, Raymond, Fowler, Sarah, Larsen, Michael D., Jablonski, Kathleen, Temprosa, Marinella, Brenneman, Tina, Edelstein, Sharon L., Abebe, Solome, Bamdad, Julie, Barkalow, Melanie, Bethepu, Joel, Bezabeh, Tsedenia, Bowers, Anna, Butler, Nicole, Callaghan, Jackie, Carter, Caitlin E., Christophi, Costas, Dwyer, Gregory M., Foulkes, Mary, Gao, Yuping, Gooding, Robert, Gottlieb, Adrienne, Grimes, Kristina L., Grover-Fairchild, Nisha, Haffner, Lori, Hoffman, Heather, Jones, Steve, Jones, Tara L., Katz, Richard, Kolinjivadi, Preethy, Lachin, John M., Ma, Yong, Mucik, Pamela, Orlosky, Robert, Reamer, Susan, Rochon, James, Sapozhnikova, Alla, Sherif, Hanna, Stimpson, Charlotte, Hogan Tjaden, Ashley, Walker-Murray, Fredricka, Venditti, Elizabeth M., Kriska, Andrea M., Weinzierl, Valerie, Marcovina, Santica, Aldrich, F. Alan, Harting, Jessica, Albers, John, Strylewicz, Greg, Killeen, Anthony, Gabrielson, Deanna, Eastman, R., Fradkin, Judith, Garfield, Sanford, Lee, Christine, Gregg, Edward, Zhang, Ping, O’Leary, Dan, Evans, Gregory, Budoff, Matthew, Dailing, Chris, Stamm, Elizabeth, Schwartz, Ann, Navy, Caroline, Palermo, Lisa, Rautaharju, Pentti, Prineas, Ronald J., Soliman, Elsayed Z., Alexander, Teresa, Campbell, Charles, Hall, Sharon, Li, Yabing, Mills, Margaret, Pemberton, Nancy, Rautaharju, Farida, Zhang, Zhuming, Hu, Julie, Hensley, Susan, Keasler, Lisa, Taylor, Tonya, Danis, Ronald, Davis, Matthew, Hubbard, Larry, Endres, Ryan, Elsas, Deborah, Johnson, Samantha, Myers, Dawn, Barrett, Nancy, Baumhauer, Heather, Benz, Wendy, Cohn, Holly, Corkery, Ellie, Dohm, Kristi, Domalpally, Amitha, Gama, Vonnie, Goulding, Anne, Ewen, Andy, Hurtenbach, Cynthia, Lawrence, Daniel, McDaniel, Kyle, Pak, Jeong, Reimers, James, Shaw, Ruth, Swift, Maria, Vargo, Pamela, Watson, Sheila, Manly, Jennifer, Mayer-Davis, Elizabeth, Moran, Robert R., Ganiats, Ted, David, Kristin, Sarkin, Andrew J., Groessl, Erik, Katzir, Naomi, Chong, Helen, Herman, William H., Brändle, Michael, Brown, Morton B., Altshuler, David, Billings, Liana K., Chen, Ling, Harden, Maegan, Pollin, Toni I., Shuldiner, Alan R., Franks, Paul W., and Hivert, Marie-France
- Subjects
Advanced and Specialized Nursing ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Pathophysiology/Complications - Abstract
OBJECTIVE To determine whether interventions that slow or prevent the development of type 2 diabetes in those at risk reduce the subsequent prevalence of diabetic retinopathy. RESEARCH DESIGN AND METHODS The Diabetes Prevention Program (DPP) randomized subjects at risk for developing type 2 diabetes because of overweight/obesity and dysglycemia to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB) to assess the prevention of diabetes. During the DPP and DPP Outcome Study (DPPOS), we performed fundus photography over time on study participants, regardless of their diabetes status. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study grading system, with diabetic retinopathy defined as typical lesions of diabetic retinopathy (microaneurysms, exudates, or hemorrhage, or worse) in either eye. RESULTS Despite reduced progression to diabetes in the ILS and MET groups compared with PLB, there was no difference in the prevalence of diabetic retinopathy between treatment groups after 1, 5, 11, or 16 years of follow-up. No treatment group differences in retinopathy were found within prespecified subgroups (baseline age, sex, race/ethnicity, baseline BMI). In addition, there was no difference in the prevalence of diabetic retinopathy between those exposed to metformin and those not exposed to metformin, regardless of treatment group assignment. CONCLUSIONS Interventions that delay or prevent the onset of type 2 diabetes in overweight/obese subjects with dysglycemia who are at risk for diabetes do not reduce the development of diabetic retinopathy for up to 20 years.
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- 2022
23. Adolescent Growth Spurt and Type 2 Diabetes Risk in Southwestern American Indians
- Author
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Ramirez-Luzuriaga, Maria J, primary, Kobes, Sayuko, additional, Sinha, Madhumita, additional, Knowler, William C, additional, and Hanson, Robert L, additional
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- 2023
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24. Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP).
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Li, Josephine H., Perry, James A., Jablonski, Kathleen A., Srinivasan, Shylaja, Chen, Ling, Todd, Jennifer N., Harden, Maegan, Mercader, Josep M., Pan, Qing, Dawed, Adem Y., Yee, Sook Wah, Pearson, Ewan R., Giacomini, Kathleen M., Giri, Ayush, Hung, Adriana M., Xiao, Shujie, Williams, L. Keoki, Franks, Paul W., Hanson, Robert L., and Kahn, Steven E.
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GENOME-wide association studies ,GENETIC variation ,GLYCOSYLATED hemoglobin ,TYPE 2 diabetes ,PROPORTIONAL hazards models - Abstract
Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 10
−9 ). In the MET arm, rs144322333 near ENOSF1 (minor allele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, β = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10−12 ). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, β = −7.55 [95% CI −9.88, −5.22]; P = 3.2 × 10−10 ) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 10−4 ]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy. [ABSTRACT FROM AUTHOR]- Published
- 2023
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25. Identification of genetic variation influencing metformin response in a multi-ancestry genome-wide association study in the Diabetes Prevention Program (DPP)
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Li, Josephine, primary, Perry, James A., primary, Jablonski, Kathleen A., primary, Srinivasan, Shylaja, primary, Chen, Ling, primary, Todd, Jennifer N., primary, Harden, Maegan, primary, Mercader, Josep M., primary, Pan, Qing, primary, Dawed, Adem Y., primary, Yee, Sook Wah, primary, Pearson, Ewan R., primary, Giacomini, Kathleen M., primary, Giri, Ayush, primary, Hung, Adriana M., primary, Xiao, Shujie, primary, Williams, L. Keoki, primary, Franks, Paul W., primary, Hanson, Robert L., primary, Kahn, Steven E., primary, Knowler, William C., primary, Pollin, Toni I., primary, Florez, Jose C., primary, and Group, Diabetes Prevention Program Research, primary
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- 2023
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26. Identification of genetic variation influencing metformin response in a multi-ancestry genome-wide association study in the Diabetes Prevention Program (DPP)
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Li, Josephine, primary, Perry, James A., primary, Jablonski, Kathleen A., primary, Srinivasan, Shylaja, primary, Chen, Ling, primary, Todd, Jennifer N., primary, Harden, Maegan, primary, Mercader, Josep M., primary, Pan, Qing, primary, Dawed, Adem Y., primary, Yee, Sook Wah, primary, Pearson, Ewan R., primary, Giacomini, Kathleen M., primary, Giri, Ayush, primary, Hung, Adriana M., primary, Xiao, Shujie, primary, Williams, L. Keoki, primary, Franks, Paul W., primary, Hanson, Robert L., primary, Kahn, Steven E., primary, Knowler, William C., primary, Pollin, Toni I., primary, Florez, Jose C., primary, and Group, Diabetes Prevention Program Research, primary
- Published
- 2022
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27. Weight Loss, Lifestyle Intervention, and Metformin Affect Longitudinal Relationship of Insulin Secretion and Sensitivity
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Vazquez Arreola, Elsa, primary, Knowler, William C, additional, and Hanson, Robert L, additional
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- 2022
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28. Increased Adiposity and Low Height-for-Age in Early Childhood Are Associated With Later Metabolic Risks in American Indian Children and Adolescents
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Ramírez-Luzuriaga, María J, primary, Kobes, Sayuko, additional, Sinha, Madhumita, additional, Knowler, William C, additional, and Hanson, Robert L, additional
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- 2022
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29. 1184-P: Adolescent Growth Spurt and Type 2 Diabetes Risk in an American Indian Population
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RAMIREZ-LUZURIAGA, MARIA J., primary, KOBES, SAYUKO, additional, SINHA, MADHUMITA, additional, KNOWLER, WILLIAM C., additional, and HANSON, ROBERT L., additional
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- 2022
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30. 141-OR: Associations between Type 2 Diabetes Partitioned/Process-Specific Polygenic Scores and Metabolic Traits
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WEDEKIND, LAUREN E., primary, HSUEH, WEN-CHI, additional, KOBES, SAYUKO, additional, BAIER, LESLIE, additional, BOGARDUS, III, CLIFTON, additional, KNOWLER, WILLIAM C., additional, MAHAJAN, ANUBHA, additional, MCCARTHY, MARK, additional, and HANSON, ROBERT L., additional
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- 2022
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31. 363-OR: Weight Loss, Lifestyle Intervention, and Metformin Effects on the Longitudinal Relationship between Insulin Secretion and Sensitivity in the Diabetes Prevention Program (DPP)
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ARREOLA, ELSA VAZQUEZ, primary, KNOWLER, WILLIAM C., additional, and HANSON, ROBERT L., additional
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- 2022
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32. 981-P: Gut Microbiome Profile of American Indian Children with Obesity and Comparison with Industrialized and Preindustrialized Microbiomes
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KOSTIC, ALEKSANDAR, primary, HANSON, ROBERT L., additional, and SINHA, MADHUMITA, additional
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- 2022
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33. Cardiorespiratory Fitness, BMI, Mortality, and Cardiovascular Disease in Adults with Overweight/Obesity and Type 2 Diabetes
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Wills, Andrew C., primary, Arreola, Elsa Vazquez, additional, Olaiya, Muideen T., additional, Curtis, Jeffrey M., additional, Hellgren, Margareta I., additional, Hanson, Robert L., additional, and Knowler, William C., additional
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- 2022
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34. Functional variants in cytochrome b5 type A (CYB5A) are enriched in Southwest American Indian individuals and associate with obesity
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Day, Samantha E., primary, Traurig, Michael, additional, Kumar, Pankaj, additional, Piaggi, Paolo, additional, Koroglu, Cigdem, additional, Kobes, Sayuko, additional, Hanson, Robert L., additional, Bogardus, Clifton, additional, and Baier, Leslie J., additional
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- 2022
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35. Weight Loss, Lifestyle Intervention, and Metformin Affect Longitudinal Relationship of Insulin Secretion and Sensitivity.
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Arreola, Elsa Vazquez, Knowler, William C., and Hanson, Robert L.
- Abstract
Context: Insulin secretion and sensitivity regulate glycemia, with inadequately compensated deficiencies leading to diabetes. Objective: We investigated effects of weight loss, an intensive lifestyle intervention (ILS), and metformin on the relationship between insulin secretion and sensitivity using repository data from 2931 participants in the Diabetes Prevention Program clinical trial in adults at high risk of developing type 2 diabetes. Methods: Insulin secretion and sensitivity were estimated from insulin and glucose concentrations in fasting and 30-minute postload serum samples at baseline and 1, 2, and 3 years after randomization, during the active intervention phase. The nonlinear relationship of secretion and sensitivity was evaluated by standardized major axis regression to account for variability in both variables. Insulin secretory demand and compensatory insulin secretion were characterized by distances along and away from the regression line, respectively. Results: ILS and metformin decreased secretory demand while increasing compensatory insulin secretion, with greater effects of ILS. Improvements were directly related to weight loss; decreased weight significantly reduced secretory demand (b=-0.144 SD; 95% CI (-0.162, -0.125)/5 kg loss) and increased compensatory insulin secretion (b=0.287 SD, 95% CI (0.261, 0.314)/5 kg loss). In time-dependent hazard models, increasing compensatory insulin secretion (hazard ratio [HR]=0.166 per baseline SD, 95% CI 0.133, 0.206) and weight loss (HR=0.710 per 5 kg loss, 95% CI 0.613, 0.819) predicted lower diabetes risk. Conclusion: Diabetes risk reduction was directly related to the amount of weight loss, an effect mediated by lowered insulin secretory demand (due to increased insulin sensitivity) coupled with improved compensatory insulin secretion. [ABSTRACT FROM AUTHOR]
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- 2022
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36. Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index
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Arreola, Elsa Vazquez, primary, Hanson, Robert L., primary, Bogardus, Clifton, primary, and Knowler, William C., primary
- Published
- 2021
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37. Relationship Between Insulin Secretion and Insulin Sensitivity and Its Role in Development of Type 2 Diabetes: Beyond the Disposition Index
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Vazquez Arreola, Elsa, primary, Hanson, Robert L., additional, Bogardus, Clifton, additional, and Knowler, William C., additional
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- 2021
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38. A missense variant Arg611Cys in LIPE which encodes hormone sensitive lipase decreases lipolysis and increases risk of type 2 diabetes in American Indians.
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Muller, Yunhua L., Sutherland, Jeff, Nair, Anup K., Koroglu, Cigdem, Kobes, Sayuko, Knowler, William C., Van Hout, Cristopher V., Shuldiner, Alan R., Hanson, Robert L., Bogardus, Clifton, and Baier, Leslie J.
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LIPOLYSIS ,TYPE 2 diabetes ,MISSENSE mutation ,LIPASES ,GLUCOSE tolerance tests ,HORMONES - Abstract
Aims: Hormone sensitive lipase (HSL), encoded by the LIPE gene, is involved in lipolysis. Based on prior animal and human studies, LIPE was analysed as a candidate gene for the development of type 2 diabetes (T2D) in a community‐based sample of American Indians. Materials and methods: Whole‐exome sequence data from 6782 participants with longitudinal clinical measures were used to identify variation in LIPE. Results: Amongst the 16 missense variants identified, an Arg611Cys variant (rs34052647; Cys‐allele frequency = 0.087) significantly associated with T2D (OR [95% CI] = 1.38 [1.17–1.64], p = 0.0002, adjusted for age, sex, birth year, and the first five genetic principal components) and an earlier onset age of T2D (HR = 1.22 [1.09–1.36], p = 0.0005). This variant was further analysed for quantitative traits related to T2D. Amongst non‐diabetic American Indians, those with the T2D risk Cys‐allele had increased insulin levels during an oral glucose tolerance test (0.07 SD per Cys‐allele, p = 0.04) and a mixed meal test (0.08 log10µU/ml per Cys‐allele, p = 0.003), and had increased lipid oxidation rates post‐absorptively and during insulin infusion (0.07 mg [kg estimated metabolic body size {EMBS}]−1 min−1 per Cys‐allele for both, p = 0.01 and 0.009, respectively), compared to individuals with the non‐risk Arg‐allele. In vitro functional studies showed that cells expressing the Cys‐allele had a 17.2% decrease in lipolysis under isoproterenol stimulation (p = 0.03) and a 21.3% decrease in lipase enzyme activity measured by using p‐nitrophenyl butyrate as a substrate (p = 0.04) compared to the Arg‐allele. Conclusion: The Arg611Cys variant causes a modest impairment in lipolysis, thereby affecting glucose homoeostasis and risk of T2D. [ABSTRACT FROM AUTHOR]
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- 2022
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39. Relationship Between Insulin Secretion and Insulin Sensitivity and Its Role in Development of Type 2 Diabetes: Beyond the Disposition Index.
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Vazquez Arreola, Elsa, Hanson, Robert L., Bogardus, Clifton, and Knowler, William C.
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TYPE 2 diabetes , *INSULIN sensitivity , *SECRETION , *INSULIN , *ORAL examinations (Education) - Abstract
We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 diabetes in American Indians participating in a longitudinal epidemiologic study. At baseline, when all participants did not have diabetes, 1,566 underwent oral tests and 420 had intravenous measures of glucose regulation, with estimates of insulin secretion and sensitivity. Standardized major axis regression was used to study the relationship between secretion and sensitivity. Distances away from and along the regression line estimated compensatory insulin secretion and secretory demand, respectively. This relationship differed according to glucose tolerance and BMI category. The distance away from the line is similar to the disposition index (DI), defined as the product of estimated secretion and sensitivity, but the regression line may differ from a line with constant DI (i.e., it is not necessarily hyperbolic). Participants with the same DI but different levels of insulin secretion and sensitivity had different incidence rates of diabetes; lower sensitivity with higher secretory demand was associated with greater diabetes risk. Insulin secretion and insulin sensitivity, analyzed together, predict diabetes better than DI alone. Physiologically, this may reflect long-term risk associated with increased allostatic load resulting from the stimulation of insulin hypersecretion by increased glycemia. [ABSTRACT FROM AUTHOR]
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- 2022
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40. Functional characterization of a novel p.Ser76Thr variant in IGFBP4that associates with body mass index in American Indians
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Muller, Yunhua L., Saporito, Michael, Day, Samantha, Bandesh, Khushdeep, Koroglu, Cigdem, Kobes, Sayuko, Knowler, William C., Hanson, Robert L., Van Hout, Cristopher V., Shuldiner, Alan R., Bogardus, Clifton, and Baier, Leslie J.
- Abstract
Insulin-like growth factor binding protein 4 (IGFBP4) is involved in adipogenesis, and IGFBP4 null mice have decreased body fat through decreased PPAR-γ expression. In the current study, we assessed whether variation in the IGFBP4coding region influences body mass index (BMI) in American Indians who are disproportionately affected by obesity. Whole exome sequence data from a population-based sample of 6779 American Indians with longitudinal measures of BMI were used to identify variation in IGFBP4that associated with BMI. A novel variant that predicts a p.Ser76Thr in IGFBP4 (Thr-allele frequency = 0.02) was identified which associated with the maximum BMI measured during adulthood (BMI 39.8 kg/m2for Thr-allele homozygotes combined with heterozygotes vs. 36.2 kg/m2for Ser-allele homozygotes, β= 6.7% per Thr-allele, p= 8.0 × 10−5, adjusted for age, sex, birth-year and the first five genetic principal components) and the maximum age- and sex-adjusted BMI z-score measured during childhood/adolescence (z-score 0.70 SD for Thr-allele heterozygotes vs. 0.32 SD for Ser-allele homozygotes, β= 0.37 SD per Thr-allele, p= 8.8 × 10−6). In vitro functional studies showed that IGFBP4 with the Thr-allele (BMI-increasing) had a 55% decrease (p= 0.0007) in FOXO-induced transcriptional activity, reflecting increased activation of the PI3K/AKT pathway mediated through increased IGF signaling. Over-expression and knock-down of IGFBP4 in OP9 cells during differentiation showed that IGFBP4 upregulates adipogenesis through PPARγ, CEBPα, AGPAT2 and SREBP1 expression. We propose that this American Indian specific variant in IGFBP4affects obesity via an increase of IGF signaling.
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- 2022
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41. Long-Term Complications in Youth-Onset Type 2 Diabetes.
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Wah Yang, Cunchuan Wang, Nelson, Robert G., Hanson, Robert L., Knowler, William C., Bjornstad, Petter, Drews, Kimberly, Zeitler, Philip S., Yang, Wah, and Wang, Cunchuan
- Subjects
- *
TYPE 1 diabetes , *TYPE 2 diabetes , *AGE factors in disease , *DISEASE complications - Published
- 2021
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42. Hepatic Insulin Resistance Increases Risk of Gallstone Disease in Indigenous Americans in the Southwestern United States.
- Author
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Aydin BN, Stinson EJ, Hanson RL, Looker HC, Cabeza De Baca T, Krakoff J, and Chang DC
- Abstract
Introduction: Animal models indicate that hepatic insulin resistance (IR) promotes cholesterol gallstone disease (GSD). We sought to determine whether hepatic and whole-body IR is associated with incident GSD., Methods: At baseline, 450 Southwestern Indigenous American adults without GSD were included. Participants had a 2-step hyperinsulinemic-euglycemic clamp with glucose tracer at submaximal and maximal insulin stimulation (240 and 2,400 pmol/m 2 /min) for whole-body IR (M-low and M-high) and hepatic glucose production (HGP) before and during submaximal insulin infusion (HGP-basal and HGP-insulin). Incident GSD was identified during follow-up visits conducted at ∼2-year intervals. The associations of HGP (basal, insulin, and % suppression), M-low, and M-high with risk of GSD were assessed by Cox regression models adjusted for age, sex, body fat (%), glucose, and insulin., Results: Sixty participants (13%) developed GSD (median follow-up: 11.6 years). Participants who developed GSD were of similar age and whole-body IR as those who did not ( P 's > 0.07) but were more likely to be female; have higher body fat, higher HGP-basal, and HGP-insulin; and lower % suppression of HGP ( P 's < 0.02). In separate adjusted models, higher HGP-insulin and lower % suppression of HGP were associated with increased risk for GSD (hazard ratio [HR] per SD: HR 1.38, 95% CI 1.12-1.69, P = 0.002; HR 1.41, 95% CI 1.16-1.72, P = 0.0007). HGP-basal, M-low, and M-high were not associated with GSD in adjusted models ( P 's > 0.22)., Discussion: Resistance to insulin suppression of HGP increases risk for GSD. Hepatic IR is a link between GSD and other conditions of the metabolic syndrome., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)
- Published
- 2024
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43. Pleiotropic effects of an eQTL in the CELSR2/PSRC1/SORT1 cluster that associates with LDL-C and resting metabolic rate.
- Author
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Bandesh K, Freeland K, Traurig M, Hanson RL, Bogardus C, Piaggi P, and Baier LJ
- Abstract
Context: The locus CELSR2-PSRC1-SORT1, a primary genetic signal for lipids, has recently been implicated in different metabolic processes. Our investigation identified its association with energy metabolism., Objective: To determine biological mechanisms that govern diverse functions of this locus., Methods: Genotypes for 491,265 variants in 7,000 clinically characterized American Indians were previously determined using a custom-designed array specific for this longitudinally studied American Indian population. Among the genotyped individuals, 5,205 had measures of fasting lipid levels and 509 had measures of resting metabolic rate (RMR) and substrate oxidation rate assessed through indirect calorimetry. A genome-wide association study (GWAS) for LDL-C levels identified a variant in CELSR2 and the molecular impact of this variant on gene expression was assessed in skeletal muscle biopsies from 207 participants, followed by functional validation in mouse myoblasts using a luciferase assay., Results: A GWAS in American Indians identified rs12740374 in CELSR2 as the top signal for LDL-C levels (P = 1 × 10-22); further analysis of this variant identified an unexpected correlation with reduced RMR (effect = -44.3 kcal/day/minor-allele) and carbohydrate oxidation rate (effect = -5.21 mg/hour/kg-EMBS). Tagged variants showed a distinct linkage disequilibrium architecture in American Indians, highlighting a potential functional variant, rs6670347 (minor-allele frequency = 0.20). Positioned in the glucocorticoid receptor's core binding motif, rs6670347 is part of a skeletal muscle-specific enhancer. Human skeletal muscle transcriptome analysis showed CELSR2 as the most differentially expressed gene (P = 1.9 × 10-7), with the RMR-lowering minor allele elevating gene expression. Experiments in mouse myoblasts confirmed enhancer-based regulation of CELSR2 expression, dependent on glucocorticoids. Rs6670347 also associated with increased oxidative phosphorylation gene expression; CELSR2 as a regulator of these genes, suggests potential influence on energy metabolism through muscle oxidative capacity., Conclusion: Variants in the CELSR2/PSRC1/SORT1 locus exhibit tissue-specific effects on metabolic traits, with an independent role in muscle metabolism through glucocorticoid signaling., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)
- Published
- 2024
- Full Text
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44. Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.
- Author
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Bradfeld JP, Kember RL, Ulrich A, Balkhiyarova Z, Alyass A, Aris IM, Bell JA, Broadaway KA, Chen Z, Chai JF, Davies NM, Fernandez-Orth D, Bustamante M, Fore R, Ganguli A, Heiskala A, Hottenga JJ, Íñiguez C, Kobes S, Leinonen J, Lowry E, Lyytikainen LP, Mahajan A, Pitkänen N, Schnurr TM, Have CT, Strachan DP, Thiering E, Vogelezang S, Wade KH, Wang CA, Wong A, Holm LA, Chesi A, Choong C, Cruz M, Elliott P, Franks S, Frithiof-Bøjsøe C, Gauderman WJ, Glessner JT, Gilsanz V, Griesman K, Hanson RL, Kaakinen M, Kalkwarf H, Kelly A, Kindler J, Kähönen M, Lanca C, Lappe J, Lee NR, McCormack S, Mentch FD, Mitchell JA, Mononen N, Niinikoski H, Oken E, Pahkala K, Sim X, Teo YY, Baier LJ, van Beijsterveldt T, Adair LS, Boomsma DI, de Geus E, Guxens M, Eriksson JG, Felix JF, Gilliland FD, Hansen T, Hardy R, Hivert MF, Holm JC, Jaddoe VWV, Järvelin MR, Lehtimäki T, Mackey DA, Meyre D, Mohlke KL, Mykkänen J, Oberfeld S, Pennell CE, Perry JRB, Raitakari O, Rivadeneira F, Saw SM, Sebert S, Shepherd JA, Standl M, Sørensen TIA, Timpson NJ, Torrent M, Willemsen G, Hypponen E, Power C, McCarthy MI, Freathy RM, Widén E, Hakonarson H, Prokopenko I, Voight BF, Zemel BS, Grant SFA, and Cousminer DL
- Published
- 2024
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45. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.
- Author
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Bradfield JP, Kember RL, Ulrich A, Balkhiyarova Z, Alyass A, Aris IM, Bell JA, Broadaway KA, Chen Z, Chai JF, Davies NM, Fernandez-Orth D, Bustamante M, Fore R, Ganguli A, Heiskala A, Hottenga JJ, Íñiguez C, Kobes S, Leinonen J, Lowry E, Lyytikainen LP, Mahajan A, Pitkänen N, Schnurr TM, Have CT, Strachan DP, Thiering E, Vogelezang S, Wade KH, Wang CA, Wong A, Holm LA, Chesi A, Choong C, Cruz M, Elliott P, Franks S, Frithioff-Bøjsøe C, Gauderman WJ, Glessner JT, Gilsanz V, Griesman K, Hanson RL, Kaakinen M, Kalkwarf H, Kelly A, Kindler J, Kähönen M, Lanca C, Lappe J, Lee NR, McCormack S, Mentch FD, Mitchell JA, Mononen N, Niinikoski H, Oken E, Pahkala K, Sim X, Teo YY, Baier LJ, van Beijsterveldt T, Adair LS, Boomsma DI, de Geus E, Guxens M, Eriksson JG, Felix JF, Gilliland FD, Biobank PM, Hansen T, Hardy R, Hivert MF, Holm JC, Jaddoe VWV, Järvelin MR, Lehtimäki T, Mackey DA, Meyre D, Mohlke KL, Mykkänen J, Oberfield S, Pennell CE, Perry JRB, Raitakari O, Rivadeneira F, Saw SM, Sebert S, Shepherd JA, Standl M, Sørensen TIA, Timpson NJ, Torrent M, Willemsen G, Hypponen E, Power C, McCarthy MI, Freathy RM, Widén E, Hakonarson H, Prokopenko I, Voight BF, Zemel BS, Grant SFA, and Cousminer DL
- Subjects
- Adult, Adolescent, Humans, Child, Child, Preschool, Puberty genetics, Phenotype, Body Height genetics, Outcome Assessment, Health Care, Longitudinal Studies, Genome-Wide Association Study, Diabetes Mellitus, Type 2
- Abstract
Background: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank., Results: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation., Conclusion: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern., (© 2023. The Author(s).)
- Published
- 2024
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46. Effects of the ABCC8 R1420H loss-of-function variant on beta-cell function, diabetes incidence, and retinopathy.
- Author
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Vazquez Arreola E, Knowler WC, Baier LJ, and Hanson RL
- Subjects
- Adult, Child, Humans, Incidence, Longitudinal Studies, Albuminuria epidemiology, Albuminuria genetics, Albuminuria complications, Cross-Sectional Studies, Sulfonylurea Receptors, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 complications, Insulin Resistance genetics, Retinal Diseases complications, Diabetes Complications complications
- Abstract
Introduction: The ABCC8 gene regulates insulin secretion and plays a critical role in glucose homeostasis. The effects of an ABCC8 R1420H loss-of-function variant on beta-cell function, incidence of type 2 diabetes, and age-at-onset, prevalence, and progression of diabetes complications were assessed in a longitudinal study in American Indians., Research Design and Methods: We analyzed beta-cell function through the relationship between insulin secretion and insulin sensitivity in members of this population without diabetes aged ≥5 years using standard major axis regression. We used hierarchical logistic regression models to study cross-sectional associations with diabetes complications including increased albuminuria (albumin-to-creatinine ratio (ACR) ≥30 mg/g), severe albuminuria (ACR ≥300 mg/g), reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m
2 ), and retinopathy. This study included 7675 individuals (254 variant carriers) previously genotyped for the R1420H with available phenotypic data and with a median follow-up time of 13.5 years (IQR 4.5-26.8)., Results: Variant carriers had worse beta-cell function than non-carriers (p=0.0004; on average estimated secretion was 22% lower, in carriers), in children and adults, with no difference in insulin sensitivity (p=0.50). At any body mass index and age before 35 years, carriers had higher type 2 diabetes incidence. This variant did not associate with prevalence of increased albuminuria (OR 0.87, 95% CI 0.66 to 1.16), severe albuminuria (OR 0.96, 95% CI 0.55 to 1.68), or reduced eGFR (OR 0.44, 95% CI 0.18 to 1.06). By contrast, the variant significantly associated with higher retinopathy prevalence (OR 1.74, 95% CI 1.19 to 2.53) and this association was only partially mediated (<11%) by glycemia, duration of diabetes, risk factors of retinopathy, or insulin use. Retinopathy prevalence in carriers was higher regardless of diabetes presence., Conclusions: The ABCC8 R1420H variant is associated with increased risks of diabetes and of retinopathy, which may be partially explained by higher glycemia levels and worse beta-cell function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2023
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47. Long-Term Complications in Youth-Onset Type 2 Diabetes.
- Author
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Nelson RG, Hanson RL, and Knowler WC
- Subjects
- Adolescent, Age of Onset, Humans, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2 complications
- Published
- 2021
- Full Text
- View/download PDF
48. Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index.
- Author
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Vazquez Arreola E, Hanson RL, Bogardus C, and Knowler WC
- Abstract
We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 diabetes in American Indians participating in a longitudinal epidemiologic study. At baseline, when all subjects did not have diabetes, 1566 participants underwent oral tests and 420 had intravenous measures of glucose regulation with estimates of insulin secretion and sensitivity. Standardized major axis regression was used to study the relationship of secretion and sensitivity. Distances away from and along the regression line estimated compensatory insulin secretion and secretory demand, respectively. This relationship differed according to glucose tolerance and BMI categories. The distance away from the line is similar to the disposition index (DI) defined as the product of estimated secretion and sensitivity, but the regression line may differ from a line with constant DI (i.e., it is not necessarily hyperbolic). Subjects with the same DI but different levels of insulin secretion and sensitivity had different incidence rates of diabetes; lower sensitivity with higher secretory demand was associated with greater diabetes risk. Insulin secretion and insulin sensitivity, analyzed together, predict diabetes better than DI alone. Physiologically, this may reflect long-term risk associated with increased allostatic load resulting from the stimulation of insulin hypersecretion by increased glycemia., (© 2021 by the American Diabetes Association.)
- Published
- 2021
- Full Text
- View/download PDF
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