Biomedical subjects

D Karasik

Publications and source records attributed to D Karasik.

At least 19 recordsLinked to original sources

PubMed2006

Proximal hip geometry is linked to several chromosomal regions: genome-wide linkage results from the Framingham Osteoporosis Study.

INTRODUCTION: Femoral geometry contributes to bone strength and predicts hip fracture risk. The purpose of this study was to evaluate heritability (h(2)) of geometric indices of the proximal hip and to perform whole-genome linkage analyses of these traits, adjusted for body size. METHODS: DXA scans of the proximal femur from 1473 members of 323 pedigrees (age range 31-96 years) from the population-based Framingham Osteoporosis Study were obtained. Using the hip structural analysis program, we measured femoral neck length (FNL, cm) and neck-shaft angle (NSA); subperiosteal width (WID, cm), cross-sectional area (CSA, cm(2)); and section modulus (Z, cm(3)) at the narrowest section of the neck (NN), intertrochanteric (IT) and femoral shaft (S) regions. Linkage analyses were performed for the above indices with a set of 636 markers using variance components maximum likelihood method. RESULTS: Substantial genetic influences were found for all geometric phenotypes, with h(2) values between 0.28 (NSA) and 0.70 (IT_WID). Adjustment for height and BMI did not alter h(2) of NSA and FNL but decreased h(2) of the cross-sectional indices. We obtained substantial linkage (multipoint LOD >3.0) for S_Z at 2p21 and 21q11 and S_WID at Xq25-q26. Inclusion of height and BMI as covariates resulted in much lower LOD scores for S_Z, whereas linkage signals for S_Z at 4q25, S_CSA at 4q32 and S_CSA and S_Z at 15q21 increased after the adjustment. Linkage of FNL at 1q and 13q, NSA at 2q and NN_WID at 16q did not change after the adjustment. CONCLUSION: Suggestive linkages of bone geometric indices were found at 1q, 2p, 4q, 13q, 15q and Xq. The identification of significant linkage regions after adjustment for BMI and height may point to QTLs influencing femoral bone geometry independent of body size.

Absorptiometry, Photon↗

PubMed2006

Abdominal aortic calcification and exostoses at the hand and lumbar spine: the Framingham Study.

Bony proliferation (exostoses) and vascular calcification are common in elderly men and women, but it is unclear whether they have a common etiology. Lateral lumbar and hand radiographs were obtained (1967-1970) in 777 men and 1,241 women (mean age 59, range 47-80 years) from the Framingham Heart Study. Each group of hand exostoses, specifically apiostoses (tufting), enthesophytes, and osteophytes, was graded on a scale of 0-3 (absent to severe) and summed across phalanges of digits 2-5. Anterior lumbar osteophytes were assessed in intervertebral spaces T12-L5 and abdominal aortic calcification (AAC) at lumbar segments L1-L4. Information on age, sex, body mass index, smoking, alcohol consumption, physical activity, systolic blood pressure, total cholesterol level, diabetes, and estrogen replacement therapy in women was obtained at the time of radiography and adjusted for in multivariate analyses. We used multivariable logistic regression models to assess the relationship between AAC (dependent variable) and exostoses for each sex. Multivariable adjusted logistic regression revealed a significant association between increased anterior lumbar osteophytes and prevalent AAC in men [odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.1-1.3 per unit increase in osteophytes] and in women (OR = 1.25, 95% CI 1.1-1.4). There also was an inverse association between enthesophytes and AAC in women only (OR = 0.82, 95% CI 0.73-0.92). Apiostoses were weakly associated with AAC in men only. Hand osteophytes were not associated with AAC. In conclusion, in this cross-sectional study, anterior lumbar osteophytes and AAC occurred in the same individuals after adjustment for age and other covariates. In general, hand exostoses were not associated with aortic calcification.

Aged↗

PubMed2004

Genome screen for a combined bone phenotype using principal component analysis: the Framingham study.

Genetic factors substantially contribute to variation in bone mass. There is a controversy as to whether shared genetic factors exist for bone mass at different sites. We hypothesize that using a composite phenotypic score of several correlated bone mass measures may provide complementary results for linkage studies. In the members of 323 pedigrees from the Framingham Osteoporosis Study, bone mineral density (BMD) was measured at the lumbar spine and three femoral sites (Lunar DPX-L), and quantitative ultrasound (QUS) measured at the calcaneus (Hologic Sahara). Data on age, sex, anthropometry, alcohol and caffeine intake, smoking status, physical activity, menopause, and estrogen use (in females) were also obtained. Principal component analyses of BMD and QUS phenotypes were performed in each sex and generation (parents and offspring). The principal component analyses yielded two components, whose loadings were extracted as principal component scores (PC1 and PC2) for each individual, with PC1 explaining up to 66% of the total variation of all bone mass measurements, and PC2 an additional 24%. Principal component analysis of the three femoral BMD measures resulted in one component (PC_hip) that explained 89-91% of the common variation of hip BMD measures. Quantitative genetic analysis (using the variance components method) revealed that both principal component scores were under significant genetic influences (covariate-adjusted heritabilities of PC1, PC2, and PC_hip were 0.66 +/- 0.07, 0.44 +/- 0.07, and 0.61 +/- 0.06, respectively). For PC1, loci of suggestive linkage were identified on chromosomes 1q21.3 and 8q24.3 with the maximum multipoint LOD scores 2.5 and 2.4, respectively. For PC2, multipoint LOD score was 2.1 on 1p36. Suggestive linkage of PC_hip was found on 8q24.3 and 16p13.2 (LODs>1.9). In conclusion, an approach to linkage analysis using the linear combination of several correlated bone phenotypes suggests that there are chromosomal loci regulating bone mass, with seemingly pleiotropic effects at different skeletal sites.

Adult↗

PubMed2003

Age, gender, and body mass effects on quantitative trait loci for bone mineral density: the Framingham Study.

A genome-wide scan was performed in participants from the Framingham Osteoporosis Study (1557 members of 330 mostly Caucasian pedigrees), with 401 microsatellite markers spaced on average at 10 cM. Bone mineral density (BMD) was measured at the femoral neck, trochanter, Ward's area, and lumbar spine with DXA. Our recent study (J Bone Mines Res 17 (2002), 1718) reported a number of regions with suggestive linkage to possible quantitative trait loci (QTL). The current study estimates the heterogeneity of linkage in these regions in subsamples of our pedigrees, stratified on the known biological contributors to bone mass of sex, age, and body mass index (BMI). The pedigree sample was stratified into three sets of subgroups by sex [males (age range 35- 96 years), females (29-91 years)], by age [60 or younger (29-60 years) and older than 60 (61-96 years)], and by BMI [stratified into low or high BMI, by median cut-off 27.7 in males (BMI range 17-53) and 25.8 in females (14-54)]. Heritability estimates of BMD (adjusted for age, anthropometry, nutrition, physical activity, and, in females, estrogen use) in subsamples ranged from 0.47 to 0.69. Two-point and multipoint variance component linkage analyses of BMD (using SOLAR) in subsamples supported findings of previously reported suggestive linkage results in the total sample on 8q24.13 and 14q31 (LODs>2.0). However, heterogeneity of linkage was observed on 6p21.2 and 21qter, where findings in the total sample were not supported by subsamples. On the other hand, subsample-specific maxima were found, on 4q34.1 (males), 9q22-9q31 (younger), 16p13.2 (high BMI), and 17p13.3 (older), which were not reflected by the total sample results. In conclusion, heterogeneity of QTL effects was revealed in pedigree members stratified by sex, age, and BMI; in some instances new loci were identified in subgroups. These findings may suggest that effects of genes on the determination of BMD differ between men and women, younger and older, and lean and obese adults. Evaluation of family members stratified in homogeneous groups may be warranted in genetic studies of bone mass.

Adult↗

PubMed2002

Insulin-like growth factor binding proteins 4 and 5 and bone mineral density in elderly men and women.

Insulin-like growth factor-1 (IGF-I) plays a central role in the maintenance of bone mass. To test whether two major IGF-I binding proteins, IGFBP-4 and IGFBP-5, are related to bone mineral density (BMD), we studied a sample of the Framingham Offspring Cohort participants (99 men and 101 women, ages 60-87). Serum levels of IGF-I, IGFBP-4, and IGFBP-5 were measured by previously validated radioimmunoassays (CVs approximately 10%). BMDs of the proximal femur and lumbar spine were measured using a Lunar DPX-L densitometer. In males, but not females, IGF-I and IGFBP-5 were inversely associated with age (r = 0.34 and r = -0.28, respectively; P <0.01), while IGFBP-4 levels were positively associated with age (P <0.01). Multivariate means for BMD (adjusted for age, body mass index, height, smoking, and in women, estrogen use) were computed across quartiles of IGFBP-4 and IGFBP-5 and IGFBP-4/IGFBP-5 ratio. In women, but not men, IGFBP-5 was positively associated with femoral neck BMD (P = 0.03), however, after statistical adjustment for IGF-I, this association was no longer significant. No other associations were observed for BMD at any other site. Further study is necessary for elucidation of the gender differences in the possible influence of IGF system components on bone mass.

Absorptiometry, Photon↗

PubMed2002

Mapping of quantitative ultrasound of the calcaneus bone to chromosome 1 by genome-wide linkage analysis.

Quantitative ultrasound (QUS) may predict the risk of fracture independent of bone density. The aim of this study was to identify, using quantitative trait linkage analysis, chromosomal regions that might contain genes influencing variation in calcaneal ultrasound measures in a set of families from the general population. A genome-wide autosomal scan was conducted in 324 Caucasian families (1270 measured individuals) from the Framingham Osteoporosis Study, using a set of 401 Marshfield microsatellite markers with a 10 cM average density map. QUS measurements included broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI). These phenotypes were regressed on age, age(2), body mass index, height, alcohol and caffeine consumption, smoking status, physical activity, and estrogen use in females, in each sex and generation separately. Adjusted QUS phenotypes demonstrated a strong heritability ranging from 0.45 (SOS) to 0.52 (BUA). By two-point variance components genome screening, phenotype-specific regions of possible linkage were identified on chromosomal regions 1p36.3 and 5p15.2. The maximum LOD score attained was 2.74 for BUA with D1S468 (4 cM) and 2.69 for SOS with D5S817 (23 cM). QUI, a linear combination of the SOS and BUA, showed linkage with both markers (LOD = 2.1 with D1S468 and LOD = 2.2 with D5S817). Results of two-point analysis were confirmed by multipoint linkage analysis only for BUA, with LOD = 2.4 at D1S468, but not for SOS or QUI. The results for QUS, adjusted for femoral and lumbar spinal bone mineral density, in addition to the above covariates, were virtually the same. In conclusion, our results suggest that there may be genetic determinants for BUA on 1p36.3. These results should encourage further investigations of the genetic source of QUS variability and candidate polymorphisms in this region.

Aged↗

PubMed2002

Genome screen for quantitative trait loci contributing to normal variation in bone mineral density: the Framingham Study.

A genome-wide scan was performed in a randomly ascertained set of 330 extended families from the population-based Framingham Study to identify chromosomal regions possibly linked to bone mineral density (BMD). A set of 401 microsatellite markers was typed at a 10-centimorgan (cM) average density throughout the genome. BMD was measured at the femoral neck, trochanter, Ward's area, and lumbar spine in 1557 participants of both Framingham cohorts. BMDs were adjusted for age, body mass index (BMI), height, alcohol, caffeine, calcium and vitamin D intakes, smoking, physical activity, and estrogen use in women within each sex and cohort. Strong heritabilities (values between 0.543 and 0.633) were found for the adjusted BMD at all sites. Two-point and multipoint quantitative linkage analyses were performed for each BMD site using the maximum likelihood variance components method. By two-point screening, loci of suggestive linkage were identified on chromosomes 6 and 21, with the maximum log10 of the odds ratio (LOD) scores of 2.34 for the trochanter at D21S1446 and 2.93 for the femoral neck at D6S2427. Lumbar spine BMD had maxima at D6S2427 (LOD = 1.88) and at D12S395 (LOD = 2.08). Multipoint linkage analysis revealed suggestive linkage of trochanteric BMD at a broad (approximately 20 cM) interval on chromosome 21q, with the peak linkage close to D21S1446 (LOD = 3.14). LOD scores were 2.13 at 8q24 with Ward's BMD and 1.92 at 14q21.3 with lumbar spine BMD. This largest genome screen to date for genes underlying normal variation in BMD, adjusted for a large number of covariates, will help to identify new positional candidate genes, otherwise unrecognized.

Aged↗

PubMed2001

The effect of season, occupation and repeated winterings on anthropologic and physiological characteristics in Russian antarctic staff.

UNLABELLED: Thirty anthropometric and ten physiological parameters were examined over a 10-month-period in 1985-86, in 66 male polar explorers, aged 25-61 years, at an Antarctic station (Mirny observatory). For 30 of these persons this was their first wintering in Antarctic while the remaining 36 had wintered there at least once before. The mentioned measurements were taken on 3 different occasions in April, September and January corresponding in the Antarctic to the beginning of the polar night and interim season period and the beginning of the polar day. Subjects of the investigation belonged to 3 occupational groups: administrative personnel, scientific staff, and manual laborers. Extended statistical analysis of the data was carried out in an attempt to distinguish the dynamics of the studied parameters in relation to the season of wintering (Climate), the number of previous winterings (Frequency), the type of occupation (Work), and their interactions. Multifactorial statistical analyses were also performed, so as to adjust for age of subjects, which is a requisite for evaluating the factor of repeating winterings, obviously age-related. Changes in a number of characteristics were clearly recognized as connected with the factor of repeating winterings, to wit: 1) Anthropometric parameters such as or subcutaneous fat and relative muscle mass; 2) Parameters pertaining to speed of neuromuscular response such as wrist muscle effort, or time of simple motor response; and 3) Physiological parameters encompassing vascular--blood pressure and respiratory--spirometric measurements. CONCLUSION: Our findings suggest that frequency of repeated winterings is not a leading factor influencing physical status of examinees. Occupational status of examinees alone or in interaction with repeated winterings and seasonal climatic factors have more prominent impact on the well-being of polar explorers.

Acclimatization↗

PubMed2000

Age assessment of Natufian remains from the land of Israel.

The Natufian population of Israel was first described by Garrod in 1932, and since then hundreds of skeletons have been discovered in archaeological excavations. Their culture is amply discussed in the literature as designating the transitional stage between extractive and productive subsistence economics in the period ca. 13,000-10,000 years BP. The Natufians represent a local population with strong biologic ties to the more ancient Upper Paleolithic inhabitants of the area. The scope of the present study is to review, on the basis of new skeletal material and new age-assessing methods, the age and sex tables attributed to this group, which usually indicate a mean age of death around 32 years.

Age Determination by Skeleton↗

PubMed2000

Evidence of major gene control of cortical bone loss in humans.

Cortical index (CI) is the ratio of the combined cortical thickness to the total diameter of the bone. It serves for the assessment of the geometric properties of bone and for indirect evaluation of bone mass. CI is a useful predictor of osteoporosis. The aim of the present study was to test the hypothesis of major gene control of CI variation in a large sample of pedigrees from Chuvashia, Russia. Complex segregation analysis revealed that the major gene model of CI inheritance is the best fitting and most parsimonious for the present data. Parameters of the genotype-gender specific dependence of CI variation on age were estimated simultaneously with other parameters in the segregation analysis. The results of analysis showed that not only the baseline level of CI but also the age at onset of the involutive bone changes (inflection point) and the rate of the CI decrease with age (slope coefficient) are under control of the same major gene. Non-major gene effects shared by pedigree members (residual familial correlations) were found to be statistically insignificant. Approximately 73% of inter-individual variation in CI was attributable to the effects explicitly included in the model.

Adolescent↗

PubMed2000

Genetic variation and covariation of parathyroid hormone levels and bone density in the human population.

The present study was an attempt to evaluate the relative importance of familial/genetic factors in interindividual variation of plasma concentrations of parathyroid hormone (PTH) and bone mineral density (BMD). We also examined to what extent common genetic and environmental factors may be involved in covariation between the hormone concentrations and BMD levels. Ninety-five nuclear pedigrees (consisting of 187 males and 168 females, aged 18-91 and 18-86 years old, respectively), from several small villages in the Chuvasha Autonomy, Russia, were assessed for PTH, sex hormones, and BMD. PTH plasma levels were measured in duplicate by immunoradiometric assay using an N-tact PTH SP kit. Standard roentgenography was done from the second and third phalanges of the middle finger on both hands for assessment of compact and cancellous bone BMD separately. The present study clearly confirmed the results of the previous genetic analyses of BMD which indicated that between 47% and 60% of the total variance of BMD, adjusted for sex and age effects, were attributable to genetic factors. Genetic factors also contributed significantly to interindividual variation of PTH. Constraining these additive genetic effects to zero dramatically increased the likelihood ratio (P < 0.001), indicating that at least 30% of the hormone plasma variation was attributable to genetic sources. The results of bivariate decomposition analysis were not clear cut. Two types of bivariate analyses showed that PTH-BMD genetic correlations according to sex and between the opposite sexes were consistently negative, but only marginally significant.

Adolescent↗

PubMed2000

Use of the hand bones roentgenographs in the prediction of age in nine human populations.

The major aim of this study was to develop an accurate method of age prediction for a wide range of ages, based on the roentgenographic assessment of the hand bones, for use in paleoanthropology and forensic medicine. The roentgenographs of the hand bones were assessed in 5756 individuals, 2683 males and 3073 females, aged 17-93 and 17-89, respectively, belonging to 9 ethnic groups from the former USSR, Israel, and Sinai peninsula (Egypt). For each roentgenogram an equidistant osteographic score (OSS) including the descriptive criteria of bone age, such as (1) osteophytes or nodes of Heberden in the periarticular regions and at sites of tendon attachment, (2) manifestations of osteoporosis, (3) signs of sclerosis, and (4) non-traumatic articular deformities, was estimated. Regression analysis, that included linear, non-linear, logistic, and stochastic models, was used to evaluate the relationships between age and OSS. This relationship was best described by a logistic regression function. Results of the logistic regression analysis clearly indicate that OSS is a strong predictor of an individual's age, with r2 values ranging from 0.671 to 0.901 (p < 0.001). Our standard errors of estimate were ranging from +/- 4.2 to +/- 7.3 years, comparing favorably with most known methods of bone age assessment. This study provides an efficient method of age prediction, which allows to extend the upper limit of prediction to the age of 70 years with acceptable accuracy.

Adolescent↗

PubMed1999

Statistical genetic analysis of plasma levels of vitamin D: familial study.

The present study attempted to evaluate the relative importance of familial/genetic factors in interindividual variation of plasma concentrations of vitamin D (calcidiol). Ninety-five nuclear pedigrees (187 males and 168 females, aged 18-91 and 18-86 years old respectively), from the Chuvasha Autonomy, Russia, were assessed for calcidiol and sex hormones. Age-adjusted 25-hydroxy-vitamin D (25OHD) measures showed very high pair-wise correlations between all members of families, which suggest that there may be a genetic factor transmitted within the families. To test this assumption, complex segregation analysis of non-adjusted 25OHD data was undertaken, in which genotype-sex specific dependence of the trait on age was incorporated. The analysis showed that some 44% of the 25OHD variance was attributable to all genetic and non-genetic factors incorporated into the model. About 22% of the variation was accounted for by a putative major gene effect.

Adolescent↗

PubMed1999

Violent mortality patterns in immigrants in Israel (1990-95).

Since 1989, a large number of immigrants, mostly from the former Soviet Union, have arrived in Israel, increasing the local population (c. 5 million) by 700,000. The morbidity and mortality of this immigrant population have been the concern of many investigations. In the present study we examine the mortality pattern of a sample of 1,000 immigrants, whose deaths occurred during the years 1990-95 and were examined at the L. Greenberg (National) Institute of Forensic Medicine. The sample was divided into two subgroups, natural and unnatural, according to manner of death. Seventy-five per cent of the victims in the violent death subgroup were males with a mean age of 44.6 (SD 17.3) years, while the females of the same category were 52.7 years old on average (SD 19.9). The age distribution of the whole sample showed peaks in the 25-34-year-old group for males and the 35-44-year-old group for females. The most frequent causes of death were accident (44.1%), suicide (12.6%) and homicide (7%). In 5% of cases the cause of death could not be determined. The pattern of mortality from violent causes in the immigrant population differed from that of the country of origin in all parameters. The incidence of unnatural death in immigrants resembled the local pattern in Israel, and was significantly lower than that of their homeland.

Accidents↗

PubMed1999

Segregation analysis reveals a major gene effect in compact and cancellous bone mineral density in 2 populations.

Involvement of genetic factors in determining bone mineral density (BMD) is doubtless. However, the exact nature of the genes governing BMD variation and sources for genetic determination of BMD of different parts of bone (compact and cancellous) have not been completely studied. The results of the complex segregation analyses performed in our previous study (Livshits et al. 1996) on a Turkmenian sample strongly support the hypothesis that a single Mendelian locus has a large effect on BMD. The parameter estimates for both types of bone tissue were so similar that we could assume a common gene effect for BMD variation of cancellous and compact bone. The objectives of the present study are to test again the possibility of major gene control of BMD in a different ethnic sample of pedigrees, namely, the Chuvasha. In addition, we report here the results of a bivariate segregation analysis of compact and cancellous BMD performed in both the Turkemenian and the Chuvasha samples of pedigrees. The results of the present study closely resemble the results obtained on the Turkmenian pedigrees. Likewise, the major finding of the present study is that there is a significant major gene effect on both compact and cancellous BMD; polygenic hypotheses were clearly rejected. Moreover, the results of the bivariate segregation analysis in both the Chuvasha and Turkmenian samples were similar. They lead to acceptance of the hypothesis that there is a single major locus with pleiotropy to both compact and cancellous bone.

Adolescent↗

PubMed1999

Anthropometric characteristics of men in Antarctica.

Thirty anthropometric and ten physiological parameters were evaluated over a 10-month period during 1985-86 in 66 polar explorers at an Antarctic station (Mirny observatory), all of them males aged 25-61 years. The evaluations were made in the months of April, September and January, which corresponded to the following Antarctic seasons: the beginning of the polar night, an intermediate period, and the beginning of the polar day; the necessary measurements were performed on subjects belonging to three occupational groups, namely: administrative, scientific, and manual workers. Significant changes in the pattern of skinfold thickness were observed using ANOVA with repeated measurements during the winter period (p < 0.05). Despite the fact that body weight and BMI of subjects remained unchanged, the mean sum of skinfold thickness and subcutaneous fat mass increased over the studied period at the expense of muscle mass. In participants engaged in high levels of outdoor physical activity (e.g. construction workers, drivers, technicians), an increase in fat mass, significant fall in muscle mass on wrist dynamometry, and protracted time of the simple motor response time was documented. Systolic blood pressure showed a downward trend during the winter in the group of manual workers, while significant rises in the diastolic pressure (p < 0.05) were found in the group of scientists at the end of the polar night. The present findings may be interpreted as evidence for destabilization in the studied individuals, and for an adaptation response to the Antarctic environment, which results in apparent increase in body fat and decrease in muscle mass.

Adaptation, Physiological↗

PubMed1998

Fluctuating asymmetry and morphometric variation of hand bones.

The major aim of this study was to test three hypotheses: 1) more complex traits of the hand are less prone to developmental insults and therefore show lower fluctuating asymmetry (FA) as compared with simple traits; 2) the manifestation of FA correlates with the variability of the trait (i.e., CV); and 3) FA is an organ-wide property, and therefore a concordance exists between the FA measures of different traits in hand bones. Seventy-two bilateral measurements of hand bones, were made from plain-film radiographs of 365 cadavers. A complex trait was considered as the total length of the three phalanges of a finger and their contiguous metacarpals. Simple traits were considered to be the lengths of individual bone that made up the complex trait. The following results were obtained: 1) on the average simple traits, composing the complex trait, show much higher FA than the corresponding complex trait, but this result is expected if there is no correlation (or low correlation) between FA of simple traits within the complex trait, due to random direction of right-left differences; 2) strong and highly significant correlation was observed between FA and CV of studied traits, regardless of sex and age of individuals; and 3) the majority of FA measurements of hand bones showed no correlation. However, correlations between some sets of FA traits were highly significant. They were interpreted, although not specifically tested, as the result of a tight relationship between traits related not only developmentally but also by active performance of the same function.

Adolescent↗

PubMedDate not supplied

Evidence on major gene control of cortical index in pedigree data from Middle Dalmatia, Croatia.

It was recently reported that the inheritance of the metacarpal cortical index (CI) in the Chuvashian population can be described in terms of a major gene (MG) model. By applying transmission probability tests, the hypothesis was accepted that not only baseline level of CI but also its sex-specific dependence on age were under control of the same putative large-effect gene. Using a pedigree sample from the population of the islands of Middle Dalmatia, Croatia (847 observed individuals in 278 pedigrees), data are presented to support the above findings. The following hypotheses were accepted: (i) inheritance of baseline CI in the Croatian population can be attributed to the effect of a MG responsible for about 42% of the variation; (ii) the same MG takes part in the control of the dependence of CI on age, particularly the age at onset of involutive bone changes (inflection point), and of the rate of decrease in CI with age (slope coefficient). Issues related to the assortative mating effect on CI and the determination of the most parsimonious model are discussed.

Adolescent↗