Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion

Transmission of the two parental alleles to offspring deviating from the Mendelian ratio is termed Transmission Ratio Distortion (TRD), occurs throughout gametic and embryonic development. TRD has been well-studied in animals, but remains largely unknown in humans. The Transmission Disequilibrium Test (TDT) was first proposed to test for association and linkage in case-trios (affected offspring and parents); adjusting for TRD using control-trios was recommended. However, the TDT does not provide risk parameter estimates for different genetic models. A loglinear model was later proposed to provide child and maternal relative risk (RR) estimates of disease, assuming Mendelian transmission. Results from our simulation study showed that case-trios RR estimates using this model are biased in the presence of TRD; power and Type 1 error are compromised. We propose an extended loglinear model adjusting for TRD. Under this extended model, RR estimates, power and Type 1 error are correctly restored. We applied this model to an intrauterine growth restriction dataset, and showed consistent results with a previous approach that adjusted for TRD using control-trios. Our findings suggested the need to adjust for TRD in avoiding spurious results. Documenting TRD in the population is therefore essential for the correct interpretation of genetic association studies

Markers of infection, breast-feeding and childhood acute lymphoblastic leukaemia

Infections are suspected to play a role in the aetiology of childhood leukaemia. In 1989–95, we evaluated the relation between childhood acute lymphoblastic leukaemia and pre- and postnatal markers of exposure to infection, as well as breast-feeding. A population-based case-control study was carried out in certain regions of Québec, Canada, in 1989–95 including 491 incident cases diagnosed between 1980 and 1993 and aged between 0 and 9 years. An identical number of healthy controls matched for age, sex and region of residence at the date of diagnosis was included. Having older siblings, mother's use of antibiotics during pregnancy, and being born second or later were all associated with increased risk of leukaemia while early day-care attendance (odds ratio (OR) = 0.49; 95% CI 0.31–0.77), and breast-feeding (OR = 0.68; 95% CI 0.49–0.95) were significantly protective. A marker of population mixing was not a risk factor. When including all variables defining family structure in a model, having older siblings at time of diagnosis was a risk factor among children diagnosed before 4 years of age (OR = 4.54; 95% CI 2.27–9.07) whereas having older siblings in the first year of life was protective among children diagnosed at 4 years of age or later (OR = 0.46; 95% CI 0.22–0.97). © 2000 Cancer Research Campaign http://www.bjcancer.co

Exploration and comparison of methods for combining population- and family-based genetic association using the Genetic Analysis Workshop 17 mini-exome

We examine the performance of various methods for combining family- and population-based genetic association data. Several approaches have been proposed for situations in which information is collected from both a subset of unrelated subjects and a subset of family members. Analyzing these samples separately is known to be inefficient, and it is important to determine the scenarios for which differing methods perform well. Others have investigated this question; however, no extensive simulations have been conducted, nor have these methods been applied to mini-exome-style data such as that provided by Genetic Analysis Workshop 17. We quantify the empirical power and false-positive rates for three existing methods applied to the Genetic Analysis Workshop 17 mini-exome data and compare relative performance. We use knowledge of the underlying data simulation model to make these assessments

Pesticide Flow Analysis to Assess Human Exposure in Greenhouse Flower Production in Colombia

Human exposure assessment tools represent a means for understanding human exposure to pesticides in agricultural activities and managing possible health risks. This paper presents a pesticide flow analysis modeling approach developed to assess human exposure to pesticide use in greenhouse flower crops in Colombia, focusing on dermal and inhalation exposure. This approach is based on the material flow analysis methodology. The transfer coefficients were obtained using the whole body dosimetry method for dermal exposure and the button personal inhalable aerosol sampler for inhalation exposure, using the tracer uranine as a pesticide surrogate. The case study was a greenhouse rose farm in the Bogota Plateau in Colombia. The approach was applied to estimate the exposure to pesticides such as mancozeb, carbendazim, propamocarb hydrochloride, fosetyl, carboxin, thiram, dimethomorph and mandipropamide. We found dermal absorption estimations close to the AOEL reference values for the pesticides carbendazim, mancozeb, thiram and mandipropamide during the study period. In addition, high values of dermal exposure were found on the forearms, hands, chest and legs of study participants, indicating weaknesses in the overlapping areas of the personal protective equipment parts. These results show how the material flow analysis methodology can be applied in the field of human exposure for early recognition of the dispersion of pesticides and support the development of measures to improve operational safety during pesticide management. Furthermore, the model makes it possible to identify the status quo of the health risk faced by workers in the study area

Reference values for an index of fetal aortic isthmus blood flow during the second half of pregnancy

ABSTRACT Objective During fetal life, the parallel position of the two cardiac ventricles confers a special status to the aortic isthmus. Flow through the isthmus reflects the balance between the performances of the two ventricles and their respective peripheral impedances. This study proposes a fetal aortic isthmus flow velocity index and its reference values defined on the basis of gestational age (GA). Methods Video recordings of 111 normal fetuses from 18 to 39 weeks of gestation were retrospectively reviewed. An isthmus flow velocity index (IFI) was calculated as follows: IFI = (systoli

Homocysteine levels in preterm infants: is there an association with intraventricular hemorrhage? A prospective cohort study.

BACKGROUND: The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia. METHODS: 123 infants \u3c 32 weeks gestation admitted to our Level III nursery were enrolled. A group of 25 term infants were enrolled for comparison. Two blood spots collected on filter paper with admission blood drawing were analyzed by a high performance liquid chromatography (HPLC) method. Statistical analysis included ANOVA, Spearman\u27s Rank Order Correlation and Mann-Whitney U test. RESULTS: The median tHcy was 2.75 micromol/L with an interquartile range of 1.34 - 4.96 micromol/L. There was no difference between preterm and term tHcy (median 2.76, IQR 1.25 - 4.8 micromol/L vs median 2.54, IQR 1.55 - 7.85 micromol/L, p = 0.07). There was no statistically significant difference in tHcy in 31 preterm infants with IVH compared to infants without IVH (median 1.96, IQR 1.09 - 4.35 micromol/L vs median 2.96, IQR 1.51 - 4.84 micromol/L, p = 0.43). There was also no statistically significant difference in tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants without PVL (median 1.55, IQR 0.25 - 3.45 micromol/L vs median 2.85, IQR 1.34 - 4.82 micromol/L, p = 0.07). Male infants had lower tHcy compared to female; prenatal steroids were associated with a higher tHcy. CONCLUSION: In our population of preterm infants, there is no association between IVH and tHcy. Male gender, prenatal steroids and preeclampsia were associated with differences in tHcy levels