Further evidence for a type 2 diabetes susceptibility locus on chromosome 11q

Duggirala, Ravindranath; Almasy, Laura; Blangero, John; Jenkinson, Christopher P.; Arya, Rector; DeFronzo, Ralph A.; Stern, Michael P.; O’Connell, P.; Boerwinkle, Eric; Buse, John B.; Ehrmann, David A.; Elbein, Steven C.; Fujimoto, Wilfred Y.; Kahn, Steven E.; Hanis, Craig L.; Mulivor, R.A.; Beck, Jeanne C.; Norris, Jill M.; Permutt, M. A.; Behn, P; Raffel, Leslie J.; Robbins, David C.

doi:10.1002/gepi.10233

Cited by 30 publications

(15 citation statements)

References 12 publications

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Section: Discussionmentioning

confidence: 99%

“…Several studies have implicated this region to contain susceptibility genes for diabetes and obesity-related phenotypes (61)(62)(63)(64). For example, the diabetes susceptibility locus found in the Pima population occurred between markers D11S4464 (123 cM, 11q24.1) and D11S912 (61), and the marker region D11S912 exhibited some evidence for linkage of diabetes in the Mexican-American population (63). A significant evidence for linkage of autosomaldominant progressive nephropathy, with features of both focal segmental glomerulosclerosis and Alport syndrome, was found near the marker D11S4464 on the chromosome 11q24 region in an Asian Indian family (65).…”

Section: Discussionmentioning

confidence: 99%

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Genotype by Diabetes Interaction Effects on the Detection of Linkage of Glomerular Filtration Rate to a Region on Chromosome 2q in Mexican Americans

Puppala

Arya

Thameem³

et al. 2007

Diabetes

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OBJECTIVE-Glomerular filtration rate (GFR) is used to assess the progression of renal disease. We performed linkage analysis to localize genes that influence GFR using estimated GFR data from the San Antonio Family Diabetes/Gallbladder Study. We also examined the effect of genotype by diabetes interaction (G ϫ DM) on the detection of linkage to address whether genetic effects on GFR differ in diabetic and nondiabetic subjects. RESEARCH DESIGN AND METHODS-GFR(N ϭ 453) was estimated using the recently recalculated Cockcroft-Gault (GFR-CGc) and the simplified Modification of Diet in Renal Disease (GFR-4VMDRD) formulae. Both estimates of GFR exhibited significant heritabilities, but only GFR-CGc showed significant G ϫ DM interaction. We therefore performed multipoint linkage analyses on both GFR measures using models that did not include G ϫ DM interaction effects (Model 1) and that included G ϫ DM interaction effects (Model 2, in the case of GFR-CGc). RESULTS-The strongest evidence for linkage (Model 1) of both GFR-CGc (logarithm of odds [LOD] 2.9) and GFR-4VMDRD (LOD 2.6) occurred between markers D9S922 and D9S1120 on chromosome 9q. However, using Model 2, the strongest evidence for linkage of GFR-CGc on chromosome 2q was found near marker D2S427 (corrected LOD score [LOD C ] 3.3) compared with the LOD score of 2.7 based on Model 1. Potential linkages (LOD or LOD C Ն1.2) were found only for GFR-CGc on chromosomes 3p, 3q, 4p, 8q, 11q, and 14q.CONCLUSIONS-We found a major locus on chromosome 2q that differentially influences GFR in diabetic and nondiabetic environments in the Mexican-American population. Diabetes

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genotype by Diabetes Interaction Effects on the Detection of Linkage of Glomerular Filtration Rate to a Region on Chromosome 2q in Mexican Americans

Puppala

Arya

Thameem³

et al. 2007

Diabetes

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“…Given the VAGES family ascertainment criteria, all of our genetic analyses incorporated correction for ascertainment bias by computing the likelihood of a pedigree conditional on the transformed triglyceride value of the proband, using the program SOLAR. Since the VAGES families had more than one proband per family, we randomly chose one of the probands from each family to correct for ascertainment bias since correcting for ascertainment bias in datasets ascertained on multiple affected probands can result in a loss of power to detect linkage (23,24). We performed simulation analysis to determine the empirical P value to verify our major linkage finding.…”

Section: Vagesmentioning

confidence: 99%

Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study

Coletta

Schneider

et al. 2009

Diabetes

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OBJECTIVE— Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS— We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES). Plasma triglyceride values were transformed, and a variance-components technique was used to conduct multipoint linkage analysis. RESULTS— After adjusting for the significant effects of sex and BMI, heritability for plasma triglycerides was estimated as 46 ± 7% ( P < 0.0001). Multipoint linkage analysis yielded the strongest evidence for linkage of plasma triglycerides near marker D12S391 on chromosome 12p (logarithm of odds [LOD] = 2.4). Our linkage signal on chromosome 12p provides independent replication of a similar finding in another Mexican-American sample from the San Antonio Family Diabetes Study (SAFDS). Combined multipoint linkage analysis of the VAGES and SAFDS data yielded significant evidence for linkage of plasma triglycerides to a genetic location between markers GATA49D12 and D12S391 on 12p (LOD = 3.8, empirical P value = 2.0 × 10 −5 ). This region on 12p harbors the gene-encoding adiponectin receptor 2 ( AdipoR2 ), where we previously have shown that multiple single nucleotide polymorphisms are associated with plasma triglyceride concentrations in the SAFDS. In the present study, we provided suggestive evidence in favor of association for rs929434 with triglyceride concentrations in the VAGES. CONCLUSIONS— Collectively, these results provide strong evidence for a major locus on chromosome 12p that influences plasma triglyceride levels in Mexican Americans.

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“…Linkage to BMI at the identical position on chromosome 11 (D11S4464) has now been replicated in Caucasians from the Framingham Heart Study (32) and obese males from Utah (33), and an adjacent region (11q22) has been linked to BMI in Nigerians (34). Linkage to type 2 diabetes, again at D11S4464, has also been replicated in Mexican Americans (35). Perhaps more importantly, linkage to type 2 diabetes on 1q21-q24 has been replicated in studies of Utah Caucasians, Old Order Amish, French, U.K., Framingham, and Chinese populations, making 1q21-q24 one of the most consistently identified regions emerging from genome-wide linkage studies of type 2 diabetes (rev.…”

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confidence: 91%