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398 results on '"Hanson, Robert L."'

1. An E115A missense variant in CERS2 is associated with increased sleeping energy expenditure and hepatic insulin resistance in American Indians

Author

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

Published
2024
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3. Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP).

Author

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.

Subjects
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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13. 28-OR: Identification of Ancestry-Specific Alleles in a Genome-Wide Association Study (GWAS) for Metformin (MET) Response in the Diabetes Prevention Program (DPP)

Author

LI, JOSEPHINE H., primary, PERRY, JAMES A., additional, JABLONSKI, KATHLEEN A., additional, CHEN, LING, additional, SRINIVASAN, SHYLAJA, additional, TODD, JENNIFER N., additional, HARDEN, MAEGAN, additional, MERCADER, JOSEP M., additional, FRANKS, PAUL W., additional, HANSON, ROBERT L., additional, KAHN, STEVEN E., additional, KNOWLER, WILLIAM C., additional, POLLIN, TONI I., additional, FLOREZ, JOSE C., additional, and GROUP, DPP RESEARCH, additional

Published
2021
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15. A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes

Author

Hanson, Robert L., Muller, Yunhua L., Kobes, Sayuko, Guo, Tingwei, Bian, Li, Ossowski, Victoria, Wiedrich, Kim, Sutherland, Jeffrey, Wiedrich, Christopher, Mahkee, Darin, Huang, Ke, Abdussamad, Maryam, Traurig, Michael, Weil, E. Jennifer, Nelson, Robert G., Bennett, Peter H., Knowler, William C., Bogardus, Clifton, and Baier, Leslie J.

Subjects
Genetic variation -- Identification and classification, Genetic susceptibility -- Research, Type 2 diabetes -- Research -- Analysis -- Genetic aspects, Health
Abstract

Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWASs) in Europeans. The current study reports a GWAS for young-onset T2DM in American Indians. Participants were selected from a longitudinal study conducted in Pima Indians and included 278 cases with diabetes with onset before 25 years of age, 295 nondiabetic controls ≥ 45 years of age, and 267 siblings of cases or controls. Individuals were genotyped on a ~1M single nucleotide polymorphism (SNP) array, resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed for association in cases and controls, and a family-based association test was conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and these SNPs were genotyped in up to 6,834 additional Pima Indians to assess replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per copy of the T allele; P = 6.6 x [10.sup.-6], which represents genome-wide significance accounting for the number of effectively independent SNPs analyzed). Transfection studies in murine pancreatic β-cells suggested that DNER regulates expression of notch signaling pathway genes. These studies implicate DNER as a susceptibility gene for T2DM in American Indians. Diabetes 2014;63:369-376 | DOI: 10.2337/db13-0416, A number of genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified (1-6). Since most established susceptibility variants were detected by genome-wide association studies (GWASs) in Europeans, [...]

Published
2014
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23. 1977-P: Whole-Exome Sequencing Followed by Functional Analysis to Identify Variants That May Influence Body Mass Index (BMI) via a Role in Adipogenesis

Author

MULLER, YUNHUA L., primary, DAY, SAMANTHA E., additional, KOROGLU, CIGDEM, additional, KOBES, SAYUKO, additional, HANSON, ROBERT L., additional, KNOWLER, WILLIAM C., additional, KIM, HYE IN, additional, HOUT, CRISTOPHER VAN, additional, GOSALIA, NEHAL, additional, SHULDINER, ALAN R., additional, BOGARDUS, CLIFTON, additional, and BAIER, LESLIE, additional

Published
2020
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24. Evaluation of A2BP1 as an Obesity Gene

Author

Ma, Lijun, Hanson, Robert L., Traurig, Michael T., Muller, Yunhua L., Kaur, Bakhshish P., Perez, Jessica M., Meyre, David, Fu, Mao, Körner, Antje, Franks, Paul W., Kiess, Wieland, Kobes, Sayuko, Knowler, William C., Kovacs, Peter, Froguel, Philippe, Shuldiner, Alan R., Bogardus, Clifton, and Baier, Leslie J.

Published
2010
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28. Linkage Disequilibrium Mapping of the Replicated Type 2 Diabetes Linkage Signal on Chromosome 1q

Author

Prokopenko, Inga, Zeggini, Eleftheria, Hanson, Robert L., Mitchell, Braxton D., Rayner, N. William, Akan, Pelin, Baier, Leslie, Das, Swapan K., Elliott, Katherine S., Fu, Mao, Frayling, Timothy M., Groves, Christopher J., Gwilliam, Rhian, Scott, Laura J., Voight, Benjamin F., Hattersley, Andrew T., Hu, Cheng, Morris, Andrew D., Ng, Maggie, Palmer, Colin N.A., Tello-Ruiz, Marcela, Vaxillaire, Martine, Wang, Cong-rong, Stein, Lincoln, Chan, Juliana, Jia, Weiping, Froguel, Philippe, Elbein, Steven C., Deloukas, Panos, Bogardus, Clifton, Shuldiner, Alan R., and McCarthy, Mark I.

Published
2009

31. Relationship Between Insulin Secretion and Insulin Sensitivity and Its Role in Development of Type 2 Diabetes: Beyond the Disposition Index.

Author

Vazquez Arreola, Elsa, Hanson, Robert L., Bogardus, Clifton, and Knowler, William C.

Subjects
*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]

Published
2022
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35. Common variation in SIM1 is reproducibly associated with BMI in Pima Indians

Author

Traurig, Michael, Mack, Janel, Hanson, Robert L., Ghoussaini, Maya, Meyre, David, Knowler, William C., Kobes, Sayuko, Froguel, Philippe, Bogardus, Clifton, and Baier, Leslie J.

Subjects
Obesity -- Risk factors -- Genetic aspects -- Demographic aspects -- Research, Pimas -- Health aspects -- Research, Genetic variation -- Research -- Health aspects -- Genetic aspects, Health, Genetic aspects, Research, Risk factors, Demographic aspects, Health aspects
Abstract

OBJECTIVE--Haploinsufficiency of SIM1 is a cause of rare monogenic obesity. To assess the role of SIM1 in polygenic obesity, this gene was analyzed in the Pima Indian population, which has a high prevalence of obesity. RESEARCH DESIGN AND METHODS--SIM1 was sequenced in 96 individuals. Variants (n = 46) were genotyped in a population-based sample of 3,250 full-heritage Pima Indians and in a separate replication sample of 2,944 predominately non-full-heritage subjects from the same community. RESULTS--Variants spanning the upstream region of SIM1 through intron 8 were associated with BMI in the full-heritage Pima Indians, where the strongest associations (P ~ [10.sup.-4] to [10.sup.-6]) were with common variants (risk allele frequency 0.61-0.67). The difference in mean BMI between individuals homozygous for the major allele compared with homozygotes for the minor allele was ~2.2 kg/[m.sup.2] (P = 2 x [10.sup.-5] for rs3213541). These associations replicated in the separate sample of subjects from the same community (P = 5 x [10.sup.-3] for rs3213541). The strongest associations (P = 4 x [10.sup.-7], controlled for age, sex, birth year, and heritage) were seen in the combined sample (n = 6,194). The risk allele for obesity was more common in full-heritage Pimas than in the mixed-heritage subjects. Two variants (rs3734353 and rs3213541) were also genotyped in 1,275 severely obese and 1,395 lean control subjects of French European ancestry. The Pima risk alleles were the minor alleles in the European samples, and these variants did not display any significant association (P > 0.05). CONCLUSIONS--Common variation in SIM1 is associated with BMI on a population level in Pima Indians where the risk allele is the major allele., Obesity is a major cause of health disparities among minority populations. The few major reports of genes contributing to polygenic obesity have predominately focused on populations of European descent. The [...]

Published
2009

36. Genome-Wide Scan for Estimated Glomerular Filtration Rate in Multi-Ethnic Diabetic Populations: The Family Investigation of Nephropathy and Diabetes (FIND)

Author

Schelling, Jeffrey R., Abboud, Hanna E., Nicholas, Susanne B., Pahl, Madeleine V., Sedor, John R., Adler, Sharon G., Arar, Nedal H., Bowden, Donald W., Elston, Robert C., Freedman, Barry I., Goddard, Katrina A.B., Guo, Xiuqing, Hanson, Robert L., Ipp, Eli, Iyengar, Sudha K., Jun, Gyungah, Kao, W. H. Linda, Kasinath, Balakuntalam S., Kimmel, Paul L., Klag, Michael J., Knowler, William C., Nelson, Robert G., Parekh, Rulan S., Quade, Shannon R., Rich, Stephen S., Saad, Mohammed F., Scavini, Marina, Smith, Michael W., Taylor, Kent, Winkler, Cheryl A., Zager, Philip G., and Shah, Vallabh O.

Published
2008

42. Genome-Wide Scans for Diabetic Nephropathy and Albuminuria in Multiethnic Populations: The Family Investigation of Nephropathy and Diabetes (FIND)

Author

Iyengar, Sudha K., Abboud, Hanna E., Goddard, Katrina A.B., Saad, Mohammed F., Adler, Sharon G., Arar, Nedal H., Bowden, Donald W., Duggirala, Ravi, Elston, Robert C., Hanson, Robert L., Ipp, Eli, Kao, W. H. Linda, Kimmel, Paul L., Klag, Michael J., Knowler, William C., Meoni, Lucy A., Nelson, Robert G., Nicholas, Susanne B., Pahl, Madeleine V., Parekh, Rulan S., Quade, Shannon R.E., Rich, Stephen S., Rotter, Jerome I., Scavini, Marina, Schelling, Jeffrey R., Sedor, John R., Sehgal, Ashwini R., Shah, Vallabh O., Smith, Michael W., Taylor, Kent D., Winkler, Cheryl A., Zager, Philip G., and Freedman, Barry I.

Published
2007

48. Variants in the [Ca.sub.v]2.3 (α1E) subunit of voltage-activated [Ca.sup.2+] channels are associated with insulin resistance and type 2 diabetes in Pima Indians

Author

Muller, Yunhua Li, Hanson, Robert L., Zimmerman, Collin, Harper, Inge, Sutherland, Jeff, Kobes, Sayuko, Knowler, William C., Bogardus, Clifton, and Baier, Leslie J.

Subjects
Genetic variation -- Research -- Health aspects -- Genetic aspects, Single nucleotide polymorphisms -- Health aspects -- Research -- Genetic aspects, Type 2 diabetes -- Risk factors -- Genetic aspects -- Research, Health, Research, Genetic aspects, Risk factors, Health aspects
Abstract

OBJECTIVE--Linkage to type 2 diabetes has been reported on chromosome 1q21-25 in Pima Indians. Fine mapping identified single nucleotide polymorphisms (SNPs) near the CACNA1E gene associated with this disease. CACNA1E [...]

Published
2007

49. IL6 Gene Promoter Polymorphisms and Type 2 Diabetes: Joint Analysis of Individual Participantsʼ Data From 21 Studies

Author

Huth, Cornelia, Heid, Iris M., Vollmert, Caren, Gieger, Christian, Grallert, Harald, Wolford, Johanna K., Langer, Birgit, Thorand, Barbara, Klopp, Norman, Hamid, Yasmin H., Pedersen, Oluf, Hansen, Torben, Lyssenko, Valeriya, Groop, Leif, Meisinger, Christa, Döring, Angela, Löwel, Hannelore, Lieb, Wolfgang, Hengstenberg, Christian, Rathmann, Wolfgang, Martin, Stephan, Stephens, Jeffrey W., Ireland, Helen, Mather, Hugh, Miller, George J., Stringham, Heather M., Boehnke, Michael, Tuomilehto, Jaakko, Boeing, Heiner, Möhlig, Matthias, Spranger, Joachim, Pfeiffer, Andreas, Wernstedt, Ingrid, Niklason, Anders, López-Bermejo, Abel, Fernández-Real, José-Manuel, Hanson, Robert L., Gallart, Luis, Vendrell, Joan, Tsiavou, Anastasia, Hatziagelaki, Erifili, Humphries, Steve E., Wichmann, H.-Erich, Herder, Christian, and Illig, Thomas

Published
2006

50. Variation Within the Gene Encoding the Upstream Stimulatory Factor 1 Does Not Influence Susceptibility to Type 2 Diabetes in Samples From Populations With Replicated Evidence of Linkage to Chromosome 1q

Author

Zeggini, Eleftheria, Damcott, Coleen M., Hanson, Robert L., Karim, Mohammad A., Rayner, N. William, Groves, Christopher J., Baier, Leslie J., Hale, Terri C., Hattersley, Andrew T., Hitman, Graham A., Hunt, Sarah E., Knowler, William C., Mitchell, Braxton D., Ng, Maggie C.Y., OʼConnell, Jeffrey R., Pollin, Toni I., Vaxillaire, Martine, Walker, Mark, Wang, Xiaoqin, Whittaker, Pamela, Kunsun, Xiang, Jia, Weiping, Chan, Juliana C. N., Froguel, Philippe, Deloukas, Panos, Shuldiner, Alan R., Elbein, Steven C., and McCarthy, Mark I.

Published
2006

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