Inheritance of Quantitative Dermatoglyphic Traits with Asymmetry and Diversity in Muzeina Bedouin Tribe: A Small Isolated and Consanguineous Population from South Sinai

The genetic factors contribute significantly to the determination of dermatoglyphic traits is well established. However, the controversies in views and findings of this issue are still inconclusive. The present study is an attempt to evaluate the inheritance of quantitative dermatoglyphic traits with asymmetry (DA and FA) and diversity (Div) through sibling correlations. Data include 218 individuals from (88 families) in a small isolate, the nomadic tribe Muzeina with a high degree of consanguinity (0.09) from South Sinai. Statistical analyses include sibling correlations, cross-correlations and genetic correlation (GC) – a ratio of sibling cross-correlation between traits divided on square root of the both traits sibling correlation product. The familial correlation coefficients for quantitative dermatoglyphic traits are perhaps expected lower in such a small isolated and consanguineous population than our previous studied in Indian populations and Chuvashian populations from Russia. These results indicate a simpler genetic basis due to high degree (0.09 inbreeding coefficient) of consanguinity in Muzeina Bedouin tribe. There is no evidence of major gene involvement, although a little genetic effect obtained from familial correlations on asymmetry (DA and FA) and diversity (Div) traits through sibling correlations. The significant interaction between sexes was found, which contradicts with the other populations perhaps due to high level of consanguinity. Lower correlation coefficients than in other non-consanguineous populations for quantitative dermatoglyphic traits indicate a simpler genetic basis due to high degree of inbreeding coefficient (0.09) in Muzeina. Dermatoglyphic asymmetry and diversity traits may be due to environmental factors rather than dominance in Bedouins, although a little genetic effect was found suggests a measure of developmental instability in human (FA)

Inheritance of Dermatoglyphic Asymmetry and Diversity Traits in Twins Based on Factor: Variance Decomposition Analysis

Dermatoglyphic asymmetry and diversity traits from a large number of twins (MZ and DZ) were analyzed based on principal factors to evaluate genetic effects and common familial environmental influences on twin data by the use of maximum likelihood-based Variance decomposition analysis. Sample consists of monozygotic (MZ) twins of two sexes (102 male pairs and 138 female pairs) and 120 pairs of dizygotic (DZ) female twins. All asymmetry (DA and FA) and diversity of dermatoglyphic traits were clearly separated into factors. These are perfectly corroborated with the earlier studies 1–3 in different ethnic populations, which indicate a common biological validity perhaps exists of the underlying component structures of dermatoglyphic characters. Our heritability result in twins clearly showed that DA_F2 is inherited mostly in dominant type (28.0%) and FA_F1 is additive (60.7%), but no significant difference in sexes was observed for these factors. Inheritance is also very prominent in diversity Factor 1, which is exactly corroborated with our previous findings4. The present results are similar with the earlier results of finger ridge count diversity in twin data5, which suggested that finger ridge count diversity is under genetic control

Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study

Low back pain (LBP) is a common musculoskeletal disorder, but it is still unclear which individuals develop it. The authors examined the contribution of genetic factors, lumbar disc degeneration (LDD) and other risk factors in a female sample of the general population. Material an

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 Brač, Hvar and Korčula and the Pelješac 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

Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation:discovering causal pathways

Rheumatoid arthritis (RA) and osteoporosis (OP) are two comorbid complex inflammatory conditions with evidence of shared genetic background and causal relationships. We aimed to clarify the genetic architecture underlying RA and various OP phenotypes while additionally considering an inflammatory component, C-reactive protein (CRP). Genome-wide association study summary statistics were acquired from the GEnetic Factors for OSteoporosis Consortium, Cohorts for Heart and Aging Research Consortium and UK Biobank. Mendelian randomization (MR) was used to detect the presence of causal relationships. Colocalization analysis was performed to determine shared genetic variants between CRP and OP phenotypes. Analysis of pleiotropy between traits owing to shared causal single nucleotide polymorphisms (SNPs) was performed using PL eiotropic A nalysis under CO mposite null hypothesis (PLACO). MR analysis was suggestive of horizontal pleiotropy between RA and OP traits. RA was a significant causal risk factor for CRP (β = 0.027, 95% confidence interval = 0.016-0.038). There was no evidence of CRP→OP causal relationship, but horizontal pleiotropy was apparent. Colocalization established shared genomic regions between CRP and OP, including GCKR and SERPINA1 genes. Pleiotropy arising from shared causal SNPs revealed through the colocalization analysis was all confirmed by PLACO. These genes were found to be involved in the same molecular function 'protein binding' (GO:0005515) associated with RA, OP and CRP. We identified three major components explaining the epidemiological relationship among RA, OP and inflammation: (1) Pleiotropy explains a portion of the shared genetic relationship between RA and OP, albeit polygenically; (2) RA contributes to CRP elevation and (3) CRP, which is influenced by RA, demonstrated pleiotropy with OP.</p

Heritability of a skeletal biomarker of biological aging

Changes in the skeletal system, which include age-related bone and joint remodeling, can potentially be used as a biomarker of biological aging. The aim of the present study was to investigate the extent and mode of inheritance of skeletal biomarker of biological aging—osseographic score (OSS), in a large sample of ethnically homogeneous pedigrees. The investigated cohort comprised 359 Chuvashian families and included 787 men aged 18–89 years (mean 46.9) and 723 women aged 18–90 years (mean 48.5). The TOSS - transformed OSS standardized in 5-year age groups for each sex, was analyzed as a BA index. We evaluated familial correlations and performed segregation analysis. Results of our study suggest the familial aggregations of TOSS variation in the Chuvashian pedigrees. In a segregation analysis we found a significant major gene (MG) effect in the individual’s TOSS with a dominant most parsimonious model (H2 = 0.32). Genetic factors (MG genotypes) explained 47% of the residual OSS variance after age adjustment and after including sex-genotype interaction, they explained 52% of the residual variance. Results of our study also indicated that the inherited difference in the skeletal aging pattern in men lies mostly in the rate of aging, but in women in the age of the onset of the period of visible skeletal changes

Contribution of Heritability and Epigenetic Factors to Skeletal Muscle Mass Variation in United Kingdom Twins

Context: Skeletal muscle mass (SMM) is one of the major components of human body composition, with deviations from normal values often leading to sarcopenia.Objective: Our major aim was to conduct a genome-wide DNA methylation study in an attempt to identify potential genomic regions associated with SMM.Design: This was a mixed cross-sectional and longitudinal study.Setting: Community-based study.Participants: A total of 1550 middle-aged UK twin (monozygotic and dizygotic) twins, 297 of which were repeatedly measured participated in the study.Main Outcome Measure: Appendicular lean mass assessed using DXA technology, and MeDIP-seq DNA methylation profiling genome-wide were obtained from each individual.Results: Heritability estimate of SMM, with simultaneous adjustment for covariates obtained using variance decomposition analysis was h2=0.809±0.050. After quality control and analysis of longitudinal stability, the DNA methylation data comprised of 723,029 genomic sites, with positive correlations between repeated measurements (Rrepeated =0.114–0.905). Correlations between MZ and DZ twins were 0.51 and 0.38 at a genome-wide average, respectively and clearly increased with Rrepeated. Testing for DNA methylation association with SMM in 50 discordant MZ twins revealed 36,081 nominally significant results, of which the top-ranked 134 signals (P&lt;0.01 and Rrepeated&gt;0.40) were subjected to replication in the sample of 1,196 individuals. Seven SMM-methylation association signals replicated at a false discovery rate &lt;0.1, and these were located in or near genes DNAH12, CAND1, CYP4F29P, ZFP64 which have previously been highlighted in muscle-related studies. Adjusting for age, smoking and blood cell heterogeneity did not alter significance of these associations.Conclusion: This epigenome-wide study, testing longitudinally stable methylation sites discovered and replicated a number of associations between DNA methylation at CpG loci and skeletal muscle mass. Four replicated signals were related to genes with potential muscle functions, suggesting that the methylome of whole blood may be informative of SMM variation<br/

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass