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Aims We aimed to determine the genetic and environmental correlation between various anthropometric indexes and incident Type 2 diabetes with a focus on waist circumference. Methods We used the data on extended Mexican-American families (808 subjects, 7617.92 person-years follow-up) from the San Antonio Family Heart Study and estimated the genetic and environmental correlations of 16 anthropometric indexes with the genetic liability of incident Type 2 diabetes. We performed bivariate trait analyses using the solar software package. Results All 16 anthropometric indexes were significantly heritable (range of heritabilities 0.24-0.99). Thirteen indexes were found to have significant environmental correlation with the liability of incident Type 2 diabetes. In contrast, only anthropometric indexes consisting of waist circumference (waist circumference, waist-hip ratio and waist-height ratio) were significantly genetically correlated (genetic correlation coefficients: 0.45, 0.55 and 0.44, respectively) with the liability of incident Type 2 diabetes. We did not observe such a correlation for BMI. Conclusions Waist circumference as a predictor of future Type 2 diabetes is supported by the finding that they share common genetic influences. [ABSTRACT FROM AUTHOR]

Objective:The SH3-domain GRB2-like (endophilin)-interacting protein 1 (SGIP1) gene has been shown to be differentially expressed in the hypothalamus of lean versus obese Israeli sand rats (Psammomys obesus), and is suspected of having a role in regulating food intake. The purpose of this study was to assess the role of genetic variation in SGIP1 in human disease.Subjects:We performed single-nucleotide polymorphism (SNP) genotyping in a large family pedigree cohort from the island of Mauritius. The Mauritius Family Study (MFS) consists of 400 individuals from 24 Indo-Mauritian families recruited from the genetically homogeneous population of Mauritius. We measured markers of the metabolic syndrome, including diabetes and obesity-related phenotypes such as fasting plasma glucose, waist:hip ratio, body mass index and fat mass.Results:Statistical genetic analysis revealed associations between SGIP1 polymorphisms and fat mass (in kilograms) as measured by bioimpedance. SNP genotyping identified associations between several genetic variants and fat mass, with the strongest association for rs2146905 (P=4.7 × 10−5). A strong allelic effect was noted for several SNPs where fat mass was reduced by up to 9.4% for individuals homozygous for the minor allele.Conclusions:Our results show association between genetic variants in SGIP1 and fat mass. We provide evidence that variation in SGIP1 is a potentially important determinant of obesity-related traits in humans. [ABSTRACT FROM AUTHOR]

Although disrupted in schizophrenia 1 (DISC1) has been implicated in many psychiatric disorders, including schizophrenia, bipolar disorder, schizoaffective disorder and major depression, its biological role in these disorders is unclear. To better understand this gene and its role in psychiatric disease, we conducted transcriptional profiling and genome-wide association analysis in 1232 pedigreed Mexican-American individuals for whom we have neuroanatomic images, neurocognitive assessments and neuropsychiatric diagnoses. SOLAR was used to determine heritability, identify gene expression patterns and perform association analyses on 188 quantitative brain-related phenotypes. We found that the DISC1 transcript is highly heritable (h2=0.50; P=1.97 × 10−22), and that gene expression is strongly cis-regulated (cis-LOD=3.89) but is also influenced by trans-effects. We identified several DISC1 polymorphisms that were associated with cortical gray matter thickness within the parietal, temporal and frontal lobes. Associated regions affiliated with memory included the entorhinal cortex (rs821639, P=4.11 × 10−5; rs2356606, P=4.71 × 10−4), cingulate cortex (rs16856322, P=2.88 × 10−4) and parahippocampal gyrus (rs821639, P=4.95 × 10−4); those affiliated with executive and other cognitive processing included the transverse temporal gyrus (rs9661837, P=5.21 × 10−4; rs17773946, P=6.23 × 10−4), anterior cingulate cortex (rs2487453, P=4.79 × 10−4; rs3738401, P=5.43 × 10−4) and medial orbitofrontal cortex (rs9661837; P=7.40 × 10−4). Cognitive measures of working memory (rs2793094, P=3.38 × 10−4), as well as lifetime history of depression (rs4658966, P=4.33 × 10−4; rs12137417, P=4.93 × 10−4) and panic (rs12137417, P=7.41 × 10−4) were associated with DISC1 sequence variation. DISC1 has well-defined genetic regulation and clearly influences important phenotypes related to psychiatric disease. [ABSTRACT FROM AUTHOR]

The hydration chemistry of sewage sludge ashes (SSAs) used as cement components is examined using X-ray diffraction, thermal analysis, and isothermal conduction calorimetry. The presence of SSA leads to the formation of significant quantities of Al2O3-Fe2O3-mono (AFm) phases. Large quantities of amorphous hydration products are also formed. An additional series of small-scale experiments is used to show that it is highly probable that amorphous or poorly crystalline hydroxyapatite (Ca5(PO4)3OH) is generated in addition to calcium silicate hydrate gel. Thus, the reactions of SSA in combination with portland cement cannot be viewed simply as comparable to the pozzolanic or latent hydraulic reactions of other by-product materials used in similar ways. [ABSTRACT FROM AUTHOR]

Paraoxonase-1 (PON1) is associated with high-density lipoprotein (HDL) particles and is believed to contribute to antiatherogenic properties of HDLs. We assessed the determinants of PON1 activity variation using different substrates of the enzyme. PON1 activity in serum samples from 922 participants in the San Antonio Family Heart Study was assayed using a reliable microplate format with three substrates: paraoxon, phenyl acetate and the lactone dihydrocoumarin. There were major differences among results from the three substrates in degree of effect by various environmental and genetic factors, suggesting that knowledge of one substrate activity alone may not provide a complete sense of PON1 metabolism. Three significant demographic covariates (age, smoking status and contraceptive usage) together explained 1–6% of phenotypic variance, whereas four metabolic covariates representing lipoprotein metabolism (apoAII, apoAI, triglycerides and non-HDL cholesterol) explained 4–19%. Genes explained 65–92% of phenotypic variance and the dominant genetic effect was exerted by a locus mapping at or near the protein structural locus (PON1) on chromosome 7. Additional genes influencing PON1 activity were localized to chromosomes 3 and 14. Our study identified environmental and genetic determinants of PON1 activity that accounted for 88–97% of total phenotypic variance, suggesting that few, if any, major biological determinants are unrepresented in the models.Heredity (2009) 102, 147–154; doi:10.1038/hdy.2008.110; published online 29 October 2008 [ABSTRACT FROM AUTHOR]

To understand the underlying genetic architecture of cardiovascular disease (CVD) risk traits, we undertook a genome-wide linkage scan to identify CVD quantitative trait loci (QTLs) in 377 individuals from the Norfolk Island population. The central aim of this research focused on the utilization of a genetically and geographically isolated population of individuals from Norfolk Island for the purposes of variance component linkage analysis to identify QTLs involved in CVD risk traits. Substantial evidence supports the involvement of traits such as systolic and diastolic blood pressures, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, body mass index and triglycerides as important risk factors for CVD pathogenesis. In addition to the environmental influences of poor diet, reduced physical activity, increasing age, cigarette smoking and alcohol consumption, many studies have illustrated a strong involvement of genetic components in the CVD phenotype through family and twin studies. We undertook a genome scan using 400 markers spaced approximately 10 cM in 600 individuals from Norfolk Island. Genotype data was analyzed using the variance components methods of SOLAR. Our results gave a peak LOD score of 2.01 localizing to chromosome 1p36 for systolic blood pressure and replicated previously implicated loci for other CVD relevant QTLs. [ABSTRACT FROM AUTHOR]

Resistin has been associated with inflammation and risk for cardiovascular disease. We previously reported evidence of a QTL on chromosome 19p13 affecting the abundance of resistin (RETN) mRNA in the omental adipose tissue of baboons (L0D score 3.8). In this study, whole genome transcription levels were assessed in human lymphocyte samples from 1240 adults participating in the San Antonio Family Heart Study, using the Sentrix Human-6 Expression Beadchip. Lymphocytes were surveyed, as it has been proposed that their expression levels may reflect those in harder to ascertain tissues, such as adipose tissue, that are thought to be more directly relevant to disease procesn was conducted to detect loci affecting RETN mRNA levels. We obtained significant evidence for a QTL influencing the RETN expression (LOD score 10.7) on chromosome 19p. This region is orthologous/homologous to the region previously localized on baboon chromosome 19. The strongest positional candidate gene in this region is the structural gene for resistin, itself. We also found evidence for a QTL influencing resistin protein levels (LOD score 5.3) on chromosome 14q. This differs from our previously reported QTL on chromosome 18 in baboons. The different QTLs for circulating protein suggests that post-translational processing and turnover may be influenced by different or multiple genes in baboons and humans. The parallel findings of a cis-eQTL for RETN mRNA in baboon omental tissue and human lymphocytes lends support to the strategy of using lymphocyte gene expression levels as a surrogate for gene expression levels in other tissues.Heredity (2008) 101, 60–66; doi:10.1038/hdy.2008.28; published online 30 April 2008 [ABSTRACT FROM AUTHOR]

The aim of this study was to examine whether genetic variation in ADIPOQ, ADIPOR1 and ADIPOR2 may contribute to increased susceptibility to components of the insulin resistance syndrome (IRS). We genotyped single-nucleotide polymorphisms (SNPs) in ADIPOQ, ADIPOR1 and ADIPOR2 in Mexican American subjects ( N=439) and performed an association analysis of IRS-related traits. Of the eight SNPs examined in the ADIPOQ gene, rs4632532 and rs182052 exhibited significant associations with BMI ( p=0.029 and p=0.032), fasting specific insulin ( p=0.023 and p=0.026), sum of skin folds (SS) ( p=0.0089 and p=0.0084) and homeostasis model assessment of insulin sensitivity (HOMA-%S) ( p=0.015 and p=0.016). Two other SNPs, rs266729 and rs2241767, were significantly associated with SS ( p=0.036 and p=0.013). SNP rs7539542 of ADIPOR1 was significantly associated with BMI, SS and waist circumference ( p=0.025, p=0.047 and p=0.0062). Fourteen of the ADIPOR2 SNPs were found to be significantly ( p<0.05) associated with fasting plasma triglyceride concentrations. Four of these SNPs (rs10848569, rs929434, rs3809266 and rs12342) were in high pairwise linkage disequilibrium ( r 2=0.99) and were strongly associated with fasting triglyceride levels ( p=0.00029, p=0.00016, p=0.00027 and p=0.00021). Adjusting for the effects of BMI and HOMA-%S on triglyceride concentrations increased significance to p=0.000060 for SNP rs929434. Bayesian quantitative trait nucleotide analysis was used to examine all possible models of gene action. Again, SNP rs929434 provided the strongest statistical evidence of an effect on triglyceride concentrations. These results provide evidence for association of SNPs in ADIPOQ and its receptors with multiple IRS-related phenotypes. Specifically, several genetic variants in ADIPOR2 were strongly associated with decreased triglyceride levels. [ABSTRACT FROM AUTHOR]

During the manufacture of Portland cement, dust is generated composed of particles of feedstock and condensed volatilised inorganic salts. Due to its highly alkaline soluble fraction, the dust can be used as an activator in blends containing pozzolanic materials or hydraulic slags, allowing them to undergo cementitious reactions. The inclusion of Portland cement in such blends enhances strength development further, although careful proportioning of materials will be required to obtain optimum performance. Ternary systems containing cement kiln dust, pulverised-fuel ash and Portland cement were characterised in this paper in terms of strength development and hydration products. For a given Portland cement content, optimum strength was achieved in blends containing approximately 10% cement kiln dust for Portland cement levels up to 80%. Beyond this level a CKD/PFA ratio of one was optimal. Isothermal conduction calorimetry results and measurements of calcium hydroxide levels indicated that this was due to an acceleration of the reactions of the blend constituents by the dust. Additionally, the chemical composition of the optimal blends promoted the production of calcium aluminate and ferrite hydrates of a type conducive to maintaining the integrity of the cementitious matrix. [ABSTRACT FROM AUTHOR]