Biomedical subjects

S K Iyengar

Publications and source records attributed to S K Iyengar.

7 recordsLinked to original sources

PubMed2007

Further evidence of pleiotropy influencing speech and language: analysis of the DYX8 region.

BACKGROUND/AIMS: Genetic studies have raised the possibility of common bases for cognitive linguistic disorders such as speech sound disorder (SSD), reading disorder (RD) and language impairment (LI). Thus, some of the same genes may jointly influence cognitive components within and between these three disorders. We examined the plausibility of this theory in a sample of families ascertained on the basis of a child with SSD. METHODS: Using the method of generalized estimating equations to solve a bivariate family predictive model we obtained measures of comorbidity and familial aggregation of SSD and LI. We then used two methods of multipoint model-free linkage analysis to evaluate SSD and LI psychometric test measures over a region previously implicated in linkage studies of RD, DYX8 region, 1p34-p36. RESULTS: Bivariate phenotypic analyses show evidence of comorbidity and within family aggregation and coaggregation of SSD and LI. In addition, two regions on chromosome 1 show suggestive evidence of linkage. The first region was previously reported in dyslexia studies. Our maximum linkage signal in this region measured articulation (p = 0.0009) in SSD sibling pairs. The second region is characterized by processes involved in language production, with the maximum linkage signal measuring listening comprehension (p = 0.0019) using all sibling pairs. CONCLUSION: We conclude that the DYX8 region could bear genes controlling pleiotropic effects on SSD, LI and RD.

Articulation Disorders↗

PubMed2005

Genome-wide search for sarcoidosis susceptibility genes in African Americans.

Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.

Black or African American↗

PubMed2001

Pooling data and linkage analysis in the chromosome 5q candidate region for asthma.

We investigated a variety of methods for pooling data from eight data sets (n = 5,424 subjects) to validate evidence for linkage of markers in the cytokine cluster on chromosome 5q31-33 to asthma and asthma-associated phenotypes. Chromosome 5 markers were integrated into current genetic linkage and physical maps, and a consensus map was constructed to facilitate effective data pooling. To provide more informative phenotypes with better distributional properties, variance component models were fitted using Gibbs sampling methods in order to generate residual additive genetic effects, or sigma-squared-A-random-effects (SSARs), which were used as derived phenotypes in subsequent linkage analyses. Multipoint estimates of alleles shared identically by descent (IBD) were computed for all full sibling pairs. Linkage analyses were performed with a new Haseman-Elston method that uses generalized-least-squares and a weighted combination of the mean-corrected trait-sum squared and trait-difference squared as the dependent variable. Analyses were performed with all data sets pooled together, and also separately with the resulting linkage statistics pooled by several meta-analytic methods. Our results provide no significant evidence that loci conferring susceptibility to asthma affection or atopy, as measured by total serum IgE levels, are present in the 5q31-33 region. This study has provided a clearer understanding of the significance, or lack of significance, of the 5q31-33 region in asthma genetics for the phenotypes studied.

Adult↗

PubMed2001

Improved evidence for linkage on 6p and 5p with retrospective pooling of data from three asthma genome screens.

To improve our ability to identify genes for complex diseases, evaluation of new methods that retrospectively pool genotype and phenotype data collected by multiple centers is important. Availability of three whole-genome screens enabled us to compare two methods, pooling raw data and meta-analysis. Multipoint linkage analyses were performed on two outcomes, total serum IgE levels and asthma affection status, using an improved Haseman-Elston algorithm. Two regions showed stronger evidence for linkage using covariate-adjusted pooled data, compared with any individual sample. Both methods for pooling data identified strong linkage to Z-transformed logeIgE levels at a location between D6S1019 and D6S426, and to the asthma trait at D5S268. In conclusion, retrospective analysis of pooled genome scan data is a potentially powerful and useful method to examine both positive and negative evidence for linkage of quantitative and categorical phenotypes across populations.

Adult↗

PubMed2001

A family-based strategy to identify genes for diabetic nephropathy.

Diabetic nephropathy (DN) clusters in families and specific ethnic groups, suggesting a genetic basis of disease transmission. Identification of DN susceptibility loci should reveal new therapeutic targets but requires accurate phenotyping. A powerful family-based strategy, which is novel to the pursuit of nephropathy genes in type 2 diabetes, is being used to collect a sample for candidate gene and genome scan analyses. Sib pairs that include DN index cases plus (1) sibs concordant for type 2 diabetes and DN (affected sib pairs [ASPs]) and (2) sibs concordant for type 2 diabetes but discordant for DN (discordant sib pairs [DSPs]) are targeted specifically for recruitment. Type 2 diabetes and DN phenotype criteria for index cases include diabetes onset after 38 years of age, duration 10 years or longer, no initial insulin treatment, diabetic retinopathy, end-stage renal disease (ESRD), and history of nephrotic proteinuria. ESRD patients were screened by questionnaire and medical record review (n = 2114). Of 666 patients with ESRD secondary to DN, 227 had a family history of ESRD, 150 had a living diabetic sib, and 124 families were enrolled. Sixty-five families, with 86 diabetic relative pairs (69 sibs, 17 children), have been completely phenotyped. If nephropathy in diabetic sibs is defined as albuminuria greater than 0.3 g/24 h, 31 ASPs and 26 DSPs (diabetic sib with albuminuria <0.3 g/24 h) were identified. Applying more stringent criteria, only 12 ASPs (sib with diabetes >10 years, diabetic retinopathy, and nephrotic proteinuria) and 9 DSPs (sib with diabetes >10 years and normal urine albumin excretion) were identified. Extrapolating from the number of subjects recruited using stringent phenotyping criteria, nearly 10,000 ESRD patients are required for screening to achieve adequate statistical power for linkage analysis (80% power to detect locus-specific relative risk of 2.2 at a lod score of 3.0). Careful phenotyping requires a large recruitment effort but is necessary to reduce population heterogeneity, a strategy that increases the likelihood of identifying DN loci.

Age of Onset↗

PubMed2000

Serum C-peptide concentrations poorly phenotype type 2 diabetic end-stage renal disease patients.

BACKGROUND: A homogeneous patient population is necessary to identify genetic factors that regulate complex disease pathogenesis. In this study, we evaluated clinical and biochemical phenotyping criteria for type 2 diabetes in end-stage renal disease (ESRD) probands of families in which nephropathy is clustered. C-peptide concentrations accurately discriminate type 1 from type 2 diabetic patients with normal renal function, but have not been extensively evaluated in ESRD patients. We hypothesized that C-peptide concentrations may not accurately reflect insulin synthesis in ESRD subjects, since the kidney is the major site of C-peptide catabolism and would poorly correlate with accepted clinical criteria used to classify diabetics as types 1 and 2. METHODS: Consenting diabetic ESRD patients (N = 341) from northeastern Ohio were enrolled. Clinical history was obtained by questionnaire, and predialysis blood samples were collected for C-peptide levels from subjects with at least one living diabetic sibling (N = 127, 48% males, 59% African Americans). RESULTS: Using clinical criteria, 79% of the study population were categorized as type 1 (10%) or type 2 diabetics (69%), while 21% of diabetic ESRD patients could not be classified. In contrast, 98% of the patients were classified as type 2 diabetics when stratified by C-peptide concentrations using criteria derived from the Diabetes Control and Complications Trial Research Group (DCCT) and UREMIDIAB studies. Categorization was concordant in only 70% of ESRD probands when C-peptide concentration and clinical classification algorithms were compared. Using clinical phenotyping criteria as the standard for comparison, C-peptide concentrations classified diabetic ESRD patients with 100% sensitivity, but only 5% specificity. The mean C-peptide concentrations were similar in diabetic ESRD patients (3.2 +/- 1.9 nmol/L) and nondiabetic ESRD subjects (3.5 +/- 1.7 nmol/L, N = 30, P = NS), but were 2.5-fold higher compared with diabetic siblings (1.3 +/- 0.7 nmol/L, N = 30, P < 0.05) with normal renal function and were indistinguishable between type 1 and type 2 diabetics. Although 10% of the diabetic ESRD study population was classified as type 1 diabetics using clinical criteria, only 1.5% of these patients had C-peptide levels less than 0.20 nmol/L, the standard cut-off used to discriminate type 1 from type 2 diabetes in patients with normal renal function. However, the criteria of C-peptide concentrations> 0.50 nmol/L and diabetes onset in patients who are more than 38 years old identify type 2 diabetes with a 97% positive predictive value in our ESRD population. CONCLUSIONS: Accepted clinical criteria, used to discriminate type 1 and type 2 diabetes, failed to classify a significant proportion of diabetic ESRD patients. In contrast to previous reports, C-peptide levels were elevated in the majority of type 1 ESRD diabetic patients and did not improve the power of clinical parameters to separate them from type 2 diabetic or nondiabetic ESRD subjects. Accurate classification of diabetic ESRD patients for genetic epidemiological studies requires both clinical and biochemical criteria, which may differ from norms used in diabetic populations with normal renal function.

Adult↗

PubMed1988

Intraoperative Doppler flow studies: emphasis on colour mapping.

Colour Doppler flow imaging (CD) is a well-established method of assessing valvular and congenital disease of the heart. The technique has proven useful intraoperatively in patients undergoing valve repair or replacement or intracardiac reconstruction. In 21 patients with various cardiac anomalies, colour Doppler flow imaging was used intraoperatively, before cardiac cannulation and again after cardiopulmonary bypass. Previously undisclosed features were demonstrated preoperatively in two patients and important residual defects after cardiopulmonary bypass in three others. Adequacy of valve replacement was confirmed in four patients and small leaks in ventricular septal defect patches were shown in another three. The procedure facilitated repair of complex cardiac fistulas in two patients. There were no apparent complications from CD. As intracardiac repairs become more complex, the role of intraoperative CD will expand.

Adult↗