Molecular basis of a linkage peak: exome sequencing and family-based analysis identify a rare genetic variant in the ADIPOQ gene in the IRAS Family Study.

Family-based linkage analysis has been a powerful tool for identification of genes contributing to traits with monogenic patterns of inheritance. These approaches have been of limited utility in identification of genes underlying complex traits. In contrast, searches for common genetic variants associated with complex traits have been highly successful.

Genetic mapping of disposition index and acute insulin response loci on chromosome 11q. The Insulin Resistance Atherosclerosis Study (IRAS) Family Study.

Glucose homeostasis, a defining characteristic of physiological glucose metabolism, is the result of complex feedback relationships with both genetic and environmental determinants that influence insulin sensitivity and beta-cell function. Relatively little is known about the genetic basis of glucose homeostasis phenotypes or their relationship to risk of diabetes. Our group previously published a genome scan for glucose homeostasis traits in 284 African-American subjects from 21 pedigrees in the Insulin Resistance Atherosclerosis Study Family Study (IRASFS) and presented evidence for linkage to disposition index (DI) on chromosome 11q with a logarithm of odds (LOD) of 3.

Association of protein tyrosine phosphatase 1B gene polymorphisms with measures of glucose homeostasis in Hispanic Americans: the insulin resistance atherosclerosis study (IRAS) family study.

Protein tyrosine phosphatase (PTP)-1B, encoded by the PTPN1 gene, catalyzes the dephosphorylation of proteins at tyrosyl residues. PTP-1B has been implicated in negatively regulating insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor. The genetic contribution of PTPN1 to measures of glucose homeostasis has been assessed in 811 Hispanic subjects from the Insulin Resistance Atherosclerosis Study Family Study (IRASFS).

Predictors of the incident metabolic syndrome in adults: the Insulin Resistance Atherosclerosis Study.

Objective: To prospectively investigate predictors of the incident metabolic syndrome in nondiabetic adults.

Research Design And Methods: This analysis included 714 white, black, and Hispanic participants in the Insulin Resistance Atherosclerosis Study (IRAS) who were free of the metabolic syndrome at baseline; 139 of these developed the metabolic syndrome in the subsequent 5 years. We examined measures of glucose (fasting and 2 h), insulin (fasting and 2 h, acute insulin response, insulin sensitivity [Si], and proinsulin), lipids (HDL and triglycerides), blood pressure (systolic and diastolic), waist circumference, and baseline physical activity (total energy expenditure) as predictors of the metabolic syndrome.