Genetic variance components analysis for binary phenotypes using generalized linear mixed models (GLMMs) and Gibbs sampling

The common complex diseases such as asthma are an important focus of genetic research, and studies based on large numbers of simple pedigrees ascertained from population‐based sampling frames are becoming commonplace. Many of the genetic and environmental factors causing these diseases are unknown and there is often a strong residual covariance between relatives even after all known determinants are taken into account. This must be modelled correctly whether scientific interest is focused on fixed effects, as in an association analysis, or on the covariances themselves. Analysis is straightforward for multivariate Normal phenotypes, but difficulties arise with other types of trait. Generalized linear mixed models (GLMMs) offer a potentially unifying approach to analysis for many classes of phenotype including multivariate Normal traits, binary traits, and censored survival times. Markov Chain Monte Carlo methods, including Gibbs sampling, provide a convenient framework within which such models may be fitted. In this paper, Bayesian inference Using Gibbs Sampling (a generic Gibbs sampler; BUGS) is used to fit GLMMs for multivariate Normal and binary phenotypes in nuclear families. BUGS is easy to use and readily available. We motivate a suitable model structure for Normal phenotypes and show how the model extends to binary traits. We discuss parameter interpretation and statistical inference and show how to circumvent a number of important theoretical and practical problems that we encountered. Using simulated data we show that model parameters seem consistent and appear unbiased in smaller data sets. We illustrate our methods using data from an ongoing cohort study. Genet. Epidemiol. 17:118–140, 1999. © 1999 Wiley‐Liss, Inc.     

Pyrogenic reactions in patients undergoing cardiac catheterization associated with contaminated glass medicine cups

Pyrogenic reactions are potentially life-threatening complications caused by bacterial endotoxin. After two cardiac catheterization patients developed rigors the same day, the procedures were halted and a case control study was conducted. To identify case patients (persons with rigors ≤3 hr after catheterization during September 25–November 9, 1995), we reviewed medical records of all cardiac catheterization patients who had a blood culture or received intravenous meperidine. Twelve case patients and 40 randomly selected control patients were identified. No specific catheter was associated with case patients, but exposure to intracoronary-nitroglycerin (NTG) was (odds ratio = 12.0; 95% confidence interval 2.2, 75.6). NTG or indocyanine green dye was poured into glass medicine cups previously washed in an enzyme cleaner and then sterilized. The cleaner, used for an entire day, had elevated levels of gram-negative bacteria (≥10⁴ colony forming units/mL) and endotoxin (434 endotoxin units [EU]/mL]); the reprocessed cups had no live bacteria but had elevated endotoxin levels (median 2,250 EU). Exposure to contaminated glass medicine cups probably resulted in pyrogenic reactions and contributed to death in two critically ill patients. Cathet. Cardiovasc. Diagn. 42:12–18, 1997. Published 1997 Wiley-Liss, Inc.     

Prevalence of Zoonotic Intestinal Helminths of Canids in Moghan Plain,Northwestern Iran

Background

The present study was aimed to elucidate the status of intestinal helminth infections in canids of Moghan Plain, northwestern Iran.

Methods

Eighty-five intestine samples from dead or shot wild canids, 59 fecal samples from sheepdogs and 5 from red foxes were collected from 2006 to 2008 and examined in Parasitology department of Pasteur Institute of Iran.

Results

Generally, adult worms, larvae, and eggs of 13 species of various parasitic helminths were recovered. Necropsy examinations showed that 96.47% animals harbored at least one helminth species. The prevalence of different species in necropsy were Mesocestoides sp. 84.7%, Rictolaria spp. 55.3%, Macranthorhynchus hirudinaceus 45.9%, Toxocara canis 43.5%, Toxascaris spp. 35.3%, Joyeuxiella sp. 34.1%; hookworms; 22.4%, Taenia spp. 11.8%, Alaria spp. 2.4% and Dipylidium caninum 1.2%. Besides, eggs belonging to 10 species of parasitic helminths were identified in 46 fecal samples and generally, 30.9% of samples harbored eggs of at least one helminth species.

Conclusion

The high prevalence of various helminth infections among canids in Moghan plain and contamination of environment by helminths eggs may increase the risk of infection for native people.     

Characterization of Eimeria Species in Commercial Broilers by PCR Based on ITS1 Regions of rDNA

Background

Coccidiosis is an intestinal disease of chickens caused by various species of protozoan parasites within the genus Eimeria. Diagnosis and genetic characterization of different species of Eimeria are central to the prevention, surveillance, and control of coccidiosis. The aim of this study was to detect different chicken Eimeria species from several areas in Khuzestan, southwest Iran.

Methods

From February to September 2008, PCR assay as well as parasitological examinations was applied for the identification of field isolates of Eimeria parasites around Ahvaz, center of Khuzestan, southwest Iran. Data were analyzed by the Kappa statistic test.

Results

Eimeria maxima, E. necatrix, E. tenella, E. acervulina and E. mitis were detected in this study. The prevalence of Eimeria spp. was 31.5% (126 of 400) and E. tenella was the most prevalent species in Khuzestan. Based on the Kappa statistical test, a good correlation between the results of PCR and traditional biometrical methods was only observed for E. maxima.

Conclusion

The present study is the first on the prevalence of Eimeria species in Khuzestan, based on the molecular findings. We believe that traditional methods are not sufficiently reliable for specific diagnosis of Eimeria species in chickens and PCR based amplification of DNA sequence of parasite, could resolve this problem.     

Depolarization properties of the optic nerve head: the effect of age

The degree of polarization (DOP) of the light reflected from the optic nerve head has been assessed by means of a polarimetric scanning laser ophthalmoscope as a function of the age of the participants. Four fundus images corresponding to independent polarization states in the recording pathway were used to compute the spatially-resolved DOP. This was not uniform across the optic nerve head and depended on both the location and the participant's age. Along a peripapillary annulus the DOP followed a double-peak pattern. Moreover, the values along this annulus decreased significantly with increasing age. This depolarization appears to originate in part in the retinal nerve fiber layer. Detailed age-dependent knowledge of the ocular depolarization properties may help to improve clinical diagnosis of the retinal nerve fiber layer.     

Investigation of the chromosome 17q25 PSORS2 locus in atopic dermatitis

Psoriasis and atopic dermatitis (AD) are strongly genetic and inherited as multi-factorial traits. In both diseases, linkage has been reported to chromosome 17q25. For psoriasis, the locus has been labelled PSORS2. Two peaks of association here contain the psoriasis candidate genes SLC9A3R (solute carrier family 9, isoform 3 regulatory factor), NAT9 (N-acetyltransferase superfamily), and RAPTOR (rapamycin (TOR)). We genotyped 14 of the most significantly associated single-nucleotide polymorphisms (SNPs) in these genes in a panel of 148 families (ECZ1) identified through a proband with active AD. The panel contains 350 siblings and 245 sib-pairs. Replication of positive findings was sought in a second panel, MRC-E, comprising of 278 families, 634 siblings, and 470 sib-pairs. SNP genotyping was carried out by Sequenom MassArray technology. Using family-based tests of association (transmission disequilibrium test), rs878906, in intron 3 of NAT9, was significantly associated with AD (P = 0.010) in the ECZ1 panel. In the MRC-E panel, rs895691, between the end of exon 6 of SLC9A3R1 and exon 7 of NAT9, was associated with AD (P = 0.037). These were not significant when multiple comparisons were taken into account. Haplotype analysis revealed no significant associations in either population. These results suggest that the psoriasis candidate genes do not account for previously observed linkage of the 17q25 PSORS2 locus to AD.