hasstedt

Common diseases such as type 2 diabetes reflect both genetic and environmental factors, complicating the identification of the underlying susceptibility genes. Applying statistical methods such as linkage and association analysis to phenotype and genotype data can help to reveal genetic risk variants. Dr. Hasstedt’s research involves both the development of methodology and software for genetic analysis and its application to family data. In addition to type 2 diabetes, her current research projects focus on venous thrombosis and obesity.

Common diseases such as type 2 diabetes reflect both genetic and environmental factors, complicating the identification of the underlying susceptibility genes. Applying statistical methods such as linkage and association analysis to phenotype and genotype data can help to reveal genetic risk variants. Dr. Hasstedt’s research involves both the development of methodology and software for genetic analysis and its application to family data. In addition to type 2 diabetes, her current research projects focus on venous thrombosis and obesity.

Dr. Hasstedt develops and distributes a software package called jPAP (Pedigree Analysis Package for Java). It applies likelihood analysis to family data to perform diverse types of analyses including linkage and association analysis. jPAP has a modular design to facilitate extension to other applications and a user-friendly interface for ease of use.

In one of two type 2 diabetes projects, linkage analysis of extended Utah families ascertained through diabetic sib pairs localized a susceptibility gene to chromosome 1. The localization has been confirmed by studies of other populations, but the causative gene remains undiscovered.

In the other type 2 diabetes project, linkage analysis of African American sibships and small pedigrees ascertained through diabetic sib pairs at ten US sites has revealed an number of potential locations of susceptibility genes. Follow up studies of the most promising have just begun.

The venous thrombosis project involves a large pedigree from Vermont. Increased risk of venous thrombosis had been partially attributed to a mutation in the protein C gene. A search for a gene that interacts with protein C to increase risk identified CADM1; the causative variant awaits discovery.

The obesity project involves a set of large Utah pedigrees identified through severely obese sib pairs. As with the other projects, the goal is to identify causative genes.

Links:

Publications in PubMed

References to Publications:

De Haan HG, Bezemer ID, Vossen CY, van Hylckama Vlieg A, Boehringer S, Hasstedt SJ, Levy S, Rosendaal FR, Bovill EG (2014) Genetic variants in cell adhesion molecule 1 (CADM1): a validation study of a novel endothelial cell venous thrombosis risk factor. Thromb Res 134:1186-1192.

Hasstedt SJ, Highland HM, Elbein SC, Hanis CL, Das SK (2013) Five Linkage Regions Each Harbor Multiple Type 2 Diabetes Genes in the African American Subset of the GENNID Study. J Hum Genet 58:378-383.

Vossen CY, Koeleman BPC, Hasstedt SJ, Nijman IJ, Renkens IJ, Callas PW, Rosendaal FR, Bovill EG (2013) Genetic variants associated with protein C levels. J Thromb Haemost 11:715-723.

Shirts BH, Howard MT, Hasstedt SJ, Nanjee MN, Knight S, Carlquist JF, Anderson JL, Hopkins PN, Hunt SC (2012) Vitamin D dependent effects of APOA5 polymorphisms on HDL cholesterol. Atherosclerosis 222:167-174.

Langberg KA, Ma L, Sharma NK, Hanis CL, Elbein SC, Hasstedt SJ, Das SK (2012) Single nucleotide polymorphisms in JAZF1 and BCL11A gene are nominally associated with type 2 diabetes in African-American families from the GENNID study. J Hum Genet 57:57-61.

Hasstedt SJ, Thomas A (2011) Detecting Pleiotropy and Epistasis using Variance Components Linkage Analysis in jPAP. Hum Hered 72:258-263.

Hunt SC, Hasstedt SJ, Xin Y, Dalley BK, Milash BA, Yakobson E, Gress RE, Davidson LE, Adams TD (2011) Polymorphisms in the NPY2R Gene Show Significant Associations With BMI That Are Additive to FTO, MC4R, and NPFFR2 Gene Effects. Obesity 19:2241-2247.

Das SK, Sharma NK, Hasstedt SJ, Mondal AK, Ma L, Langberg KA, Elbein SC (2011) An integrative genomics approach identifies activation of thioredoxin/thioredoxin reductase-1-mediated oxidative stress defense pathway and inhibition of angiogenesis in obese nondiabetic human subjects. J Clin Endocrinol Metab 96:E1308-1313.

Meltzer ME, Hasstedt SJ, Vossen CY, Callas PW, DE Groot PG, Rosendaal FR, Lisman T, Bovill EG (2011) Genome scan of clot lysis time and its association with thrombosis in a protein C-deficient kindred. J Thromb Haemost 9:1383-1390.

Hasstedt SJ, Hanis CL, Elbein SC (2010) Univariate and bivariate linkage analysis identifies pleiotropic loci underlying lipid levels and type 2 diabetes risk. Ann Hum Genet 74:308-315.

Hasstedt SJ, Xin Y, Hopkins PN, Hunt SC (2010) Two-dimensional, sex-specific autosomal linkage scan of the number of sodium pump sites. J Hypertens 28:740-747

Hasstedt SJ, Bezemer ID, Callas PW, Vossen CY, Trotman W, Hebbel RP, Demers C, Rosendaal FR, Bovill EG (2009) Cell adhesion molecule 1: a novel risk factor for venous thrombosis. Blood 114:3084-3091.

Butterfield RJ, Ramachandran D, Hasstedt SJ, Otterud BE, Leppert MF, Swoboda KJ, Flanigan KM (2009) A novel form of juvenile recessive ALS maps to loci on 6p25 and 21q22. Neuromuscul Disord19:279-287.

Elbein SC, Das SK, Hallman DM, Hanis CL, Hasstedt SJ (2009) Genome-wide linkage and admixture mapping of type 2 diabetes in African American families from the American Diabetes Association GENNID (Genetics of NIDDM) study cohort. Diabetes 58:268-274.

Hasstedt SJ, Chu WS, Das SK, Wang H, Elbein SC (2008) Type 2 diabetes susceptibility genes on chromosome 1q21-24. Ann Hum Genet 72:163-169.

Hasstedt SJ, Scott BT, Rosendaal FR, Callas PW, Vossen CY, Long GL, Bovill EG (2007) Exclusion of the alpha(2) subunit of platelet-activating factor acetylhydrolase 1b(PAFAH1B2) as a prothrombotic gene in a protein C-deficient kindred and population-based case-control sample. Thromb Haemost 98:587-592.

Vossen CY, Callas PW, Hasstedt SJ, Long GL, Rosendaal FR, Bovill EG (2007) A genetic basis for the interrelation of coagulation factors. J Thromb Haemost 5:1930-1935.

Elbein SC, Chu WS, Das SK, Yao-Borengasser A, Hasstedt SJ, Wang H, Rasouli N, Kem PA (2007) Transcription factor 7-like 2 polymorphisms and type 2 diabetes, glucose homeostasis traits and gene expression in US participants of European and African descent. Diabetologia 50:1621-1630.

Das SK, Chu WS, Hale TC, Wang X, Craig RL, Wang H, Shuldiner AR, Froguel P, Deloukas P, McCarthy MI, Zeggini E, Hasstedt SJ, Elbein SC (2006) Polymorphisms in the glucokinase-associated, dual-specificity phosphatase 12 (DUSP12) gene under chromosome 1q21 linkage peak are associated with type 2 diabetes. Diabetes 55:2631-2619.

Vossen CY, Hasstedt SJ, Demers C, Rosendaal FR, Bovill EG (2007) Linkage analysis for three coagulation factors clustering on chromosome 13q34: factor VII, factor X and protein Z. J Thromb Haemost 5:1325-1327.

Malhotra A, Elbein SC, Ng MC, Duggirala R, Arya R, Imperatore G, Adeyemo A, Pollin TI, Hsueh WC, Chan JC, Rotimi C, Hanson RL, Hasstedt SJ, Wolford JK (2006) Meta-analysis of genome-wide linkage studies of quantitative lipid traits in families ascertained for type 2 diabetes. Diabetes 56:890-896.

Das SK, Chu WS, Hale TC, Wang X, Craig RL, Wang H, Shuldiner AR, Froguel P, Deloukas P, McCarthy MI, Zeggini E, Hasstedt SJ, Elbein SC (2006) Polymorphisms in the glucokinase-associated, dual-specificity phosphatase 12 (DUSP12) gene under chromosome 1q21 linkage peak are associated with type 2 diabetes. Diabetes 55:2631-2619.

Vossen CY, Hasstedt SJ, Scott BT, Rosendaal FR, Bovill EG (2006) A genome search for genetics determinants of markers of protein C activation. J Thromb Haemost 4:706-708.

Hunt SC, Xin Y, Wu LL, Cawthon RM, Coon H, Hasstedt SJ, Hopkins PN (2005) Sodium bicarbonate cotransporter polymorphisms are associated with baseline and 10-year follow-up blood pressures. Hypertension 47:532-536.

Coon H, Xin Y, Hopkins PN, Cawthon RM, Hasstedt SJ, Hunt SC (2005) Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglycerides. Hum Genet 117:444-451.

Malhotra A, Cromer K, Leppert MF, Hasstedt SJ (2005) The power to detect genetic linkage for quantitative traits in the Utah CEPH pedigrees. J Hum Genet 50:69-75.

Principal Investigator

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Sandra Hasstedt, PH.D.

Associate Professor

Address

Department of Human Genetics
University of Utah
Human Genetics
15 N 2030 E RM 2100
Salt Lake City, Utah 84112-5330

Phone

801-581-4565

Fax

801-581-7796