Biomedical subjects

Emil Ginsburg

Publications and source records attributed to Emil Ginsburg.

5 recordsLinked to original sources

PubMed2005

Segregation analysis of systolic and diastolic blood pressure in Middle Dalmatia Island population.

A complex segregation analysis of systolic and diastolic blood pressure has been performed on pedigree data from rural populations inhabiting Middle Dalmatian islands of Brac, Hvar and Korcula and the Peljesac peninsula. The purpose of the performed analysis was to possibly elucidate a signal of a large-effect gene responsible for high prevalence of hypertension present in this population (the age-adjusted prevalence of developed hypertension being 31.82% in males and 28.23% in females). The analysis was performed on a sample of 389 two- and three-generation families consisting of 2 to 19 observed individuals (1126 examinees in total, 526 males and 600 females, aged 17 to 83). Since the examinees were randomly selected from census data encompassing 22.6% of the total population--the family relations having been established afterwards--the selected sample can be considered representative for the examined populations. By applying the usual transmission probability tests, the major gene model has been accepted for systolic as well as for diastolic blood pressure. The most parsimonious models showed that: (a) inheritance of blood pressure in the Middle Dalmatia population can be attributed to the effect of a major gene responsible for 34% (systolic) and 36% (diastolic) blood pressure variation; (b) alleles of that major gene act in co-dominant fashion; (c) allele frequency for high blood pressure (A2) is 18% (systolic) and 15% (diastolic blood pressure); and (d) the residual (non-major gene) familial correlation is negligible and can be constrained to zero. Since the results are also indicating heterogeneity within the sample in the genetic determination of the systolic blood pressure, the obtained results thus justify further search for the most promising subpopulation for incoming genetic epidemiological investigations of hypertension.

Adult↗

PubMed2004

Sampling correction in linkage analysis.

In a linkage analysis that requires the estimation of parameters other than the recombination fraction, we can construct a pedigree likelihood that leads to consistent parameter estimators if the sampling procedures are known. In particular, it is necessary to identify the subset of pedigree members "relevant to sampling" (RS), where by sampling we mean both pedigree ascertainment through a proband combination and the selective inclusion of the sampled pedigrees in the data that are analyzed. If both these procedures are independent of the marker phenotypes and the model of trait inheritance is known, then no sampling or ascertainment correction is needed to obtain a consistent estimator of the recombination fraction. Otherwise, the correction can be of two types: sampling-model-based, in which the ascertainment and inclusion procedures are modeled and used in the likelihood expression, or sampling-model-free, in which the data RS are "conditioned out" without any modeling of the sampling procedures. In either case, the pedigree proband sampling frame must be identified.

Chromosome Mapping↗

PubMed2003

Sampling correction in pedigree analysis.

Usually, a pedigree is sampled and included in the sample that is analyzed after following a predefined non-random sampling design comprising several specific procedures. To obtain a pedigree analysis result free from the bias caused by the sampling procedures, a correction is applied to the pedigree likelihood. The sampling procedures usually considered are: the pedigree ascertainment, determining whether a population unit is to be sampled; the intrafamilial pedigree extension, determining what part of the pedigree is to be sampled; and selective censoring of the sampled pedigree, determining whether it should be included in the sample to be analyzed. The probability of pedigree ascertainment is determined by the total set of potential probands in the true pedigree from which the sampled pedigree is obtained and we indicate how the necessary information on this set can be collected. If insufficient information on this set is observed, it is impossible to correct the pedigree likelihood adequately. Here we show that, if only the structure of this set is known, then an ascertainment-model-based pedigree likelihood can be obtained by conditioning on this structure. An ascertainment-model-free (AMF) pedigree likelihood can be correctly constructed by conditioning on all the data in this set, i.e. on both its structure and its phenotypic content. However, if this set has missing data, the AMF likelihood becomes undefined, which limits the utility of this AMF approach originally proposed by Ewens and Shute (1986). We also consider the sampling correction necessary when the pedigrees included in the sample analyzed have been subjected to censoring. The forms of likelihood correction developed here provide asymptotically unbiased estimators of the genetic model only if the formulated model is correct, which means that it must correctly allow for the most important features of the true inheritance of the trait studied. Otherwise, if no special case of the formulated general model is close to the true inheritance model, then the forms of likelihood correction proposed here result in biases, the magnitude and direction of which depend on both the true model and the general analysis model that should subsume it.

Journal Article↗

PubMed2003

Complex segregation analysis of body height, weight and BMI in pedigree data from Middle Dalmatia, Croatia.

It has recently been reported that the mode of inheritance of body height, weight and BMI in five ethnically and geographically different populations can be described in terms of a major gene (MG) model. Here, using the pedigree sample from the island populations of Middle Dalmatia, Croatia (1,312 observed individuals in 462 pedigrees), the evidence is presented that supports the above findings. By applying the usual transmission probability tests, the hypothesis has been accepted that a significant part of the variation of each one of those three basic morphological traits can be attributed to the effect of a putative large-effect gene. The effect of a putative MG is responsible for 39-50% of age and sex adjusted trait's variation and for 34-48% of the total (non age-adjusted) variation of height, weight and BMI.

Adolescent↗

PubMed2002

Increase in power of transmission-disequilibrium tests for quantitative traits.

Allison ([1997] Am. J. Hum. Genet. 60:676-690) proposed four versions of the transmission-disequilibrium test (TDT) for quantitative traits when there is extreme-threshold sampling, i.e., the trios having an offspring trait value between a priori defined thresholds are excluded from the analysis. Keeping intact the ideology and construction of these tests, we propose here an extreme-offspring design for the trios: for each parent pair of which at least one is heterozygous at a marker locus, the offspring having the most extreme trait value is selected for the trio. Our simulation studies show that the effect of the extreme-offspring design can be quite substantial (up to 30% increase in test power), and that the increase is greater for smaller values of the association parameter and for traits with smaller heritability: just those cases where the increase in power is especially desirable.

Data Interpretation, Statistical↗