Biomedical subjects

Ida Malkin

Publications and source records attributed to Ida Malkin.

18 recordsLinked to original sources

PubMed2006

Changes in reproductive indices in Chuvashian women whose maturation was during World War II.

OBJECTIVES: The aim of the present study was to evaluate whether Chuvashian women whose maturation was during World War II and the subsequent rehabilitation period were different from women born at other times in terms of age at menarche and age at menopause. DESIGN: The cohort included 745 Chuvashian females aged 18-90 years; age at menarche (N=653), ranged from 10 to 24 years (mean 15.42+/-2.11). Data regarding menopausal age was obtained from 322 females born between 1915 and 1950 (mean 48.5+/-4.6). We computed descriptive statistics of the age of menopause and the age of menarche for different birth cohorts; we compared the mean values by Student's t-test and the variances by F-test. RESULTS: The "expected" maturation period of women whose age at menarche >20 and most women whose age at menopause < or =38 was between 1939 and 1950. Women whose age at menarche >20 showed normal parameters regarding age at menopause, and women whose age at menopause was < or =38 showed normal parameters of age at menarche. The variances of age at menopause in women born from 1925 to 1936 was almost two-fold higher than in women born earlier and afterwards (p=0.0003). The difference in the mean ages was significant for both menarche (p=0.005) and menopause (p=0.001). CONCLUSION: Periods of socioeconomic disasters such as war and famine can influence women's age at menarche and age at menopause. Women, whose maturation occurred during or immediately after World War II, showed a higher mean age at menarche and a wider dispersion of age at menopause than other women.

Adolescent↗

PubMed2006

Strong association between polymorphisms in ANKH locus and skeletal size traits.

Loss of bone strength is the main determinant of bone fragility. Bone strength is directly dependent on bone size (BS). A substantial portion of BS variation is attributable to genetic effects. However, the list of genes and allelic variants involved in the determination of BS variation is far from being complete. Polymorphisms in the ANKH gene have been shown to be associated with radiographic hand BS-related phenotypes. The present study examined the possible association of the ANKH gene with skeletal size and shape in order to test the universality of the ANKH effect on BS traits. Our sample consisted of a total of 212 ethnically homogeneous nuclear families (743 individuals) of European origin. Each individual was measured for body height, weight, and several other anthropometrical measurements, and genotyped for nine polymorphic markers (the average heterozygosity level was 0.4). We observed significant associations with practically all the anthropometrical phenotypes studied. More specifically, we found associations with body weight and height, limb length (P</=0.001; promoter region). After adjustment for body height, we demonstrated the substantial association increase for biacromial breadth (P=0.0012; some 140 kb downstream from ANKH) and vertebral column length (P=0.0008; exons 2-7 region). The majority of the observed associations persisted even after correction for multiple testing. For the first time the reliable evidence in support of universality of ANKH gene polymorphisms effect on bone size was provided.

Adolescent↗

PubMed2006

The association between morbidity and radiographic hand osteoarthritis: a population-based study.

OBJECTIVES: Osteoarthritis is the most common form of joint disease and is considered to be a risk factor for other morbidities. We performed a population-based study to evaluate the association between morbidity and radiographic hand osteoarthritis. METHODS: Our population consisted of Chuvashians residing in peripheral villages of the Russian Federation. The investigated cohort included 434 males aged 18-86 years and 385 females aged 18-84 years. Osteoarthritis development was evaluated using the Kellgren and Lawrence grading scheme. Morbidity data was attained from their medical records and divided into 14 categories by an experienced research physician. To explore the relationship between morbidity and age-adjusted radiographic hand osteoarthritis score, one-way analysis of variance was used, with hand osteoarthritis score as a dependent variable and individuals affected vs. non-affected with the specific disease as an independent (grouping) variable. RESULTS AND CONCLUSIONS: Statistically significant evidence linking radiographic hand osteoarthritis and morbidities was found in patients with ischemic heart disease and gastrointestinal diseases. Our research indicates that individuals with ischemic heart disease have higher values of radiographic hand osteoarthritis, compared to lower values in individuals with gastrointestinal diseases. Additional research is needed to understand the biological mechanisms of the association between morbidity and osteoarthritis.

Adolescent↗

PubMed2005

Variation in femoral length is associated with polymorphisms in RUNX2 gene.

INTRODUCTION: Bone size is an important determinant of bone strength. Although it is well established that bone size traits are under the strong genetic control, genes involved in their determination are poorly characterized. The major objective of the present study was to test hypothesis of possible association between three RUNX2 SNP polymorphisms (rs2819858, rs1406846, rs2819854) and anthropometrical femoral length (FEML). In addition, the possibility of association between anthropometrical tibial length (TIBL) and stature and chosen RUNX2 polymorphisms was tested. MATERIALS AND METHODS: The study was conducted on 265 nuclear families comprised of a total of 904 individuals. DNA samples were available for 705 individuals, belonging to 212 nuclear families. Three different transmission disequilibrium tests (TDTs), population-based and pedigree-based (PDT) association analyses were implemented in order to test the working hypothesis. RESULTS: The results unambiguously and consistently demonstrated significant association for FEML regardless of the specific polymorphism tested and type of analysis implemented. The P values obtained by TDTs ranged between 0.0155 and 0.0007. The effect of RUNX2 polymorphisms was estimated to explain 1.9% of the total FEML variation after adjustment for sex and age. The data suggested that the strength of association between RUNX2 polymorphisms and FEML may be higher in females (P = 0.007) than in males (P = 0.046), according to PDT. Conversely, no reliable evidence of association between RUNX2 polymorphisms and either TIBL or stature was found. CONCLUSIONS: For the first time, the evidence of association between RUNX2 polymorphisms and FEML was provided. The results of the present research contribute to the deeper understanding of the genetic architecture of femoral size and introduce the issues of site and sex dependency of the extent of RUNX2 effect. Further studies are required to confirm our findings, specifically focused on clinically oriented sites of skeleton, like femoral neck.

Adolescent↗

PubMed2005

Association of ENPP1 gene polymorphisms with hand osteoarthritis in a Chuvasha population.

Periarticular calcification is a common attendant symptom of generalized arterial calcification of infancy, a rare Mendelian disorder caused by mutations of the gene coding for ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). This prompted us to perform a family-based association study to test the hypothesis that genetic variation at the ENPP1 locus is involved in the etiology of osteoarthritis of the hand. The study population comprised 126 nuclear families with 574 adult individuals living in small villages in the Chuvasha and Bashkirostan autonomies of the Russian Federation. The extent of osteoarthritis was determined by analyzing plain hand radiographs. The outcome of a principal component analysis of osteoarthritis scores of a total of 28 joints of both hands was used as a primary phenotype in this study. Maximum likelihood estimates of the variance component analysis revealed a substantial contribution of genetic factors to the overall trait variance of about 25% in this homogeneous population. Three short tandem repeat (STR) polymorphisms--one intragenic and two flanking markers--and four single-nucleotide polymorphisms were tested. The markers tagged the ENPP1 locus at nearly equal intervals. We used three different transmission disequilibrium tests and obtained highly significant association signals. Alleles of the upstream microsatellite marker as well as several single-nucleotide polymorphism haplotypes consistently revealed the association. Thus, our data highlights variability of ENPP1 as an important genetic factor in the pathogenesis of idiopathic osteoarthritis.

Adolescent↗

PubMed2005

Association between physique characteristics and hand skeletal aging status.

The aim of the present study was to evaluate the association between skeletal aging traits (obtained from evaluation of hand radiographs) and physique characteristics, including indices of obesity, skeletal size, muscular development, and the somatotypes of Heath and Carter (1967) and of Deriabin (1985). To achieve our aims, we used multiple regression analysis, and Pearson's and canonical correlation analyses. The studied population comprised 629 males and 561 females aged 18-90 years, all members of the Chuvasha (Russian Federation). The present study provides evidence for a connection between hand bone aging traits and physique characteristics. The cortical index showed a small but significant correlation with adiposity and the index of overall physique, but bone mineral density (BMD) traits were not correlated with the index of overall physique. Deriabin's set of somatotypes was significantly correlated with BMD, but could explain only 2% of its variation. Significant correlations of the hand osteoarthritis trait were observed with indices of adiposity. Also observed were statistically significant canonical correlations with both sets of somatotypes, which enabled us to predict 2-3% of hand osteoarthritis variation by a combination of somatotype components. Osseometric score evinced statistically significant correlations with most indices of physique as well as with a combination of somatotype components. These findings may prove helpful in epidemiological studies, because they show that body composition is the factor that is statistically significantly associated with skeletal aging.

Adipose Tissue↗

PubMed2005

Association of ANKH gene polymorphisms with radiographic hand bone size and geometry in a Chuvasha population.

We performed a family-based association study to test the hypothesis that genetic variation at the human orthologue of the mouse progressive ankylosis gene (ANKH) is involved in determining bone size (BS) and bone geometry (BG). The study population comprised 126 nuclear families with 574 adult Chuvashian individuals living in small villages in the Russian Federation. Quantitative bone traits were determined by analyzing plain hand radiographs. Familial correlations for all studied traits revealed a high degree of heritability in this ethnically homogeneous population. Three simple tandem repeat (STR) polymorphisms, one intragenic and two flanking markers, as well as six single nucleotide polymorphisms (SNPs) were tested. The SNPs were detected by re-sequencing experiments and covered ANKH exons with their flanking splice sites and the promoter region. We used three different transmission disequilibrium tests (TDTs) and obtained multiple significant association signals for all investigated bone traits. Alleles of several markers located at different positions of the ANKH locus, including the promoter, consistently revealed the association. The bone traits tested are closely related to bone fragility suggesting a role for ANKH in osteoporosis.

Adolescent↗

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↗

PubMed2004

Lack of evidence for a major gene in the Mendelian transmission of BMI in Chinese.

OBJECTIVES: To determine the heritability of BMI and to examine the mode of inheritance of BMI variation in Chinese. RESEARCH METHODS AND PROCEDURES: Familial correlation and complex segregation analyses for BMI were undertaken in a Chinese sample composed of 392 nuclear families, with 1190 total individuals. RESULTS: A moderate heritability was found for BMI (h2 = 0.419-0.492). The obtained results do not support a major gene for BMI in our samples. BMI may be inherited in a complex and non-Mendelian manner in Chinese. DISCUSSION: The findings of this study suggest that identification of specific genes for BMI in Chinese, at least within the same data set, is a serious challenge because of the lack of evidence of a major gene for BMI in our Chinese sample.

Aged↗

PubMed2004

Israeli jewish infants of different descent: growth patterns, likeness and differences. Longitudinal study.

BACKGROUND: Due to increasing migration process and intermarriages among individuals belonging to different ethnic groups, it is important to examine whether intermixing of populations effects child growth rate. AIMS: To compare growth patterns of Jewish infants from distinct descent. SUBJECTS: 1300 Israeli children were divided into 7 groups: 4 groups of babies with both parents from the same geographic origin (Europe, Yemen, Middle East or North Africa) and 3 inter-mixed groups according to genetic distances between the parents' derivation. STUDY DESIGN: The studied infants were monitored longitudinally for both body length. weight and head circumference from birth until 20 months of life. Using the curve fitting technique the follow-up data were fitted to the 3-parameter Count model. OUTCOME MEASUREMENTS: Three sets of maximal likelihood estimates of the model parameters were obtained to test the growth patterns of different groups of Jewish children: individually-specific for every child, group specific for each individual within the group, and general for all individuals from all studied groups. Likelihood ratio test was used to examine whether the chosen function of trait dependence on age is uniformly reliable for all individuals from all the considered groups. RESULTS AND CONCLUSIONS: Significant differences were indicated between all studied growth curves for all three studied traits. Moreover, distances calculated between the studied cohorts demonstrated a clear distinction between the clusters of "non-mixed" and "mixed" groups for length and weight. Since the studied children were born and developed in similar environments, these results may serve as important evidence for the existence of a genetic effect on the growth process.

Body Height↗

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

Cortical index and size of hand bones: segregation analysis and linkage with the 11q12-13 segment.

BACKGROUND: Bone geometry (BG) and size (BS) are important factors in determining bone fragility. Previous studies have suggested that more than half of BG and BS variation is genetically determined. The possible chromosomal locations of genes involved in BS and BG determination have not been explored. We evaluated the extent and mode of inheritance of the radiographic hand BS index (BSI) and the metacarpal cortical index (MCI), and tested the hypothesis of linkage between these traits and the 11q 12-13 chromosomal region. MATERIAL/METHODS: Hand radiographs and blood samples were collected from 1190 individuals belonging to 349 Chuvasha nuclear families (Russian Federation). Segregation analysis was conducted on a total sample. Transmission disequilibrium testing (TDT) and model-based linkage analyses (MBLA) were performed on a sub-sample of 163 families. RESULTS: The hypothesis of a major gene effect was confirmed for both studied traits. The best-fitting models were Mendelian, with an additive type of inheritance. The inferred major gene explained 50% of the CI and 40% of the BSI variation. The TDT and MBLA results did not permit confirmation of hypotheses about linkage between hand BSI and the 11q 12-13 chromosomal region, but a possible linkage between CI and that region cannot be ruled out. CONCLUSIONS: We support the hypothesis of a major gene effect in the heritability of BSI and MCI. We provide suggestive evidence for possible linkage disequilibrium between MCI and the 11q12-13 chromosomal segment (marker D11S1983), but not for a linkage between BSI and this

Adolescent↗

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↗

PubMedDate not supplied

Variation of skeletal biomarkers of biological aging in a Chuvashian population: a longitudinal study.

Osseographic score (OSS) is a skeletal biomarker of biological aging, based on assessment of the hand's radiographic features. The aims of the present cross-sectional and follow-up study were: 1) to evaluate age-related changes of OSS in a large Chuvashian cohort, and 2) to evaluate sex differences in age-related changes of OSS. This study reports on intersexual differences in the pattern of skeletal aging. The most prominent difference was in the rate of skeletal change, measured as average OSS difference per year. However, no differences were found in the age at which the first skeletal change occurred. The mean values of OSS were higher in males than in females in decades 3-5 of life, but afterwards they reversed. In a follow-up study, we found that sex differences regarding the rate of OSS change began in the fifth decade, but became statistically significant only in the sixth and seventh decades. Thereafter, the rate of OSS change again became virtually equal between sexes.

Adult↗

PubMedDate not supplied

Age at menarche in a Chuvashian rural population.

OBJECTIVES: The secular trend and familial influences on age at menarche among a rural Chuvashian population was examined in a cross-sectional community-based study. SUBJECTS AND METHODS: The cohort included 617 females aged 18-80 years, with age at menarche ranging from 10 to 24 years (mean 15.4 +/- 2.1). Statistical analyses included simple linear regression, maximum likelihood estimation and a whiskers plot. RESULTS: Women born during the second through the fourth decade of the 20th century showed increasing mean values of age at menarche from 15.4 (second decade) up to 16.5 (fourth decade). Women born after the fourth decade showed a decrease in mean values from 15.5 (fifth decade) to 13.0 (ninth decade). The highest peak of age at menarche was in women born in 1932. Significant familial correlations were observed between adjusted to year of birth age at menarche in mothers and daughters r = 0.195, p<0.01 and sisters and sisters r = 0.404, p<0.01. CONCLUSION: Our study demonstrated the certain secular trends of age at menarche in Chuvashian women who matured after World War II. Periods of socio-economic disasters such as war and famine disrupt the secular trend. Our findings also confirm the hypothesis of significant familial influences on menarcheal age.

Adolescent↗

PubMedDate not supplied

Time-related trends of age at menopause and reproductive period of women in a Chuvashian rural population.

OBJECTIVE: The objective of this study was to examine in an observational, cross-sectional, community-based study the secular trend of age at menopause among women in a rural Chuvashian population and to identify factors associated with age at menopause. DESIGN: The sample included 316 postmenopausal women born between 1920 and 1950 with mean age at menopause of 48.47 +/- 4.63 (34-58) years. Statistical analyses included simple and multiple linear regression and "whiskers" plots. RESULTS: Significant association was found between year of birth and age at menopause (beta = 0.194, P < 0.001) and reproduction period (P = 0.193, P < 0.001). Mean values of age at menopause increased from 47.0 years (born during 1920-1925) to maximal values of 49.7 years (born during 1940-1945) and 49.3 years (born during 1945-1950). Mean values of their reproductive period increased from 30.7 (born during 1920-1925) to maximal values of 34.1 (born during 1940-1945) and to 33.7 (born during 1945-1950). Multiple linear regression analysis demonstrated that year of birth was the only statistically significant (P = 0.19, P < 0.01) predictor of age at menopause. Age at menarche can also be a possible predictor of age at menopause (beta = -0.12, P = 0.04). CONCLUSIONS: The study confirmed certain secular trends of age at menopause and reproductive periods in Chuvashian women. The authors also observed a negative association between age at menarche and age at menopause. The number of children and medical abortions as well as body mass index showed no association with age at menopause.

Adult↗