Insights into the pleiotropic relationships between chronic back pain and inflammation-related musculoskeletal conditions: rheumatoid arthritis and osteoporotic abnormalities.

ABSTRACT: The ageing process includes the development of debilitating musculoskeletal (MSK) conditions, including chronic back pain (CBP), rheumatoid arthritis (RA), and osteoporosis (OP). The mechanisms involved in the genetic-epidemiological relationships between these MSK phenotypes are controversial and limited and thus require clarification, in particular, between CBP and the other MSK phenotypes. A cross-sectional statistical analysis was conducted using Europeans from the UK Biobank data collection, including 73,794 CBP, 4883 RA, and 7153 OP cases as well as 242,216 calcaneus bone mineral density scores. C-reactive protein (CRP) was measured for 402,165 subjects in this sample. Genetic correlations were assessed to evaluate shared genetic background between traits. Mendelian randomization was performed to assess a causal relationship between CBP and RA and OP along with other risk factors, such as CRP. Colocalization analysis was conducted to identify shared pleiotropic regions between the examined traits. Bayesian modelling was performed to determine a potential pathway that may explain the interrelationships among these traits. Mendelian randomization analyses revealed that CRP causally predicts CBP only (ß = 0.183, 95% CI = 0.077-0.290, P -value = 0.001). Horizontally pleiotropy appeared to explain the relationship between CBP and RA and OP. Through colocalization analysis, several genomic regions emerged describing common genetic influences between CBP and its proposed risk factors, including HLA-DQA1/HLA-DQB1, APOE , SOX5, and MYH7B as well as Histone 1 genes. We speculate that among other factors, CBP and its MSK comorbidities may arise from common inflammatory mechanisms. Colocalized identified genes may aid in advancing or improving the mode of treatment in patients with CBP.

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 (ß = 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.

Shared Genetic Architecture Between Rheumatoid Arthritis and Varying Osteoporotic Phenotypes.

Rheumatoid arthritis (RA) and low bone mineral density (BMD), an indicator of osteoporosis (OP), appear epidemiologically associated. Shared genetic factors may explain this association. This study aimed to investigate the presence of pleiotropy to clarify the potential genetic association between RA and OP. We examined BMDs at varying skeletal sites reported in UK Biobank as well as OP fracture acquired from the Genetic Factors for Osteoporosis (GEFOS) Consortium and the TwinsUK study. PRSice-2 was used to assess the potential shared genetic overlap between RA and OP. The presence of pleiotropy was examined using colocalization analysis. PRSice-2 revealed that RA was significantly associated with OP fracture (ß = 351.6 ± 83.9, p value = 2.76E-05), total BMD (ß = -1763.5 ± 612.8, p = 4.00E-03), spine BMD (ß = -919.8 ± 264.6, p value = 5.09E-04), and forearm BMD (ß = -66.09 ± 31.40, p value = 3.53E-02). Through colocalization analysis, the same causal genetic variants, associated with both RA and OP, were apparent in 12 genes: PLCL1, BOLL, AC011997.1, TNFAIP3, RP11-158I9.1, CDK6, CHCHD4P2, RP11-505C13.1, PHF19, TRAF1, C5, and C11orf49 with moderate posterior probabilities (>50%). Pleiotropy is involved in the association between RA and OP phenotypes. These findings contribute to the understanding of disease mechanisms and provide insight into possible therapeutic advancements and enhanced screening measures. © 2021 American Society for Bone and Mineral Research (ASBMR).

Self-reported hearing loss questions provide a good measure for genetic studies: a polygenic risk score analysis from UK Biobank.

Age-related hearing impairment (ARHI) is very common in older adults and has major impact on quality of life. The heritability of ARHI has been estimated to be around 50%. The present study aimed to estimate heritability and environmental contributions to liability of ARHI and the extent to which a polygenic risk score (PRS) derived from a recent genome-wide association study of questionnaire items regarding hearing loss using the UK Biobank is predictive of hearing loss in other samples. We examined (1) a sample from TwinsUK who have had hearing ability measured by pure-tone audiogram and the speech-to-noise ratio test as well as questionnaire measures that are comparable with the UK Biobank questionnaire items and (2) European and non-European samples from the UK Biobank which were not part of the original GWAS. Results indicated that the questionnaire items were over 50% heritable in TwinsUK and comparable with the objective hearing measures. In addition, we found very high genetic correlation (0.30-0.84) between the questionnaire responses and objective hearing measures in the TwinsUK sample. Finally, PRS computed from weighted UK Biobank GWAS results were predictive of both questionnaire and objective measures of hearing loss in the TwinsUK sample, as well as questionnaire-measured hearing loss in Europeans but not non-European subpopulations. These results demonstrate the utility of questionnaire-based methods in genetic association studies of hearing loss in adults and highlight the differences in genetic predisposition to ARHI by ethnic background.

Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways.

Chronic widespread musculoskeletal pain (CWP) and frailty are prevalent conditions in older people. We have shown previously that interindividual variation in frailty and CWP is genetically determined. We also reported an association of frailty and CWP caused by shared genetic and common environmental factors. The aim of this study was to use omic approaches to identify molecular genetic factors underlying the heritability of frailty and its genetic correlation with CWP. Frailty was quantified through the Rockwood Frailty Index (FI) as a proportion of deficits from 33 binary health deficit questions in 3626 female twins. Common widespread pain was assessed using a screening questionnaire. OMICS analysis included 305 metabolites and whole-genome (>2.5 × 10 SNPs) and epigenome (∼1 × 10 MeDIP-seq regions) assessments performed on fasting blood samples. Using family-based statistical analyses, including path analysis, we examined how FI scores were related to molecular genetic factors and to CWP, taking into account known risk factors such as fat mass and smoking. Frailty Index was significantly correlated with 51 metabolites after correction for multiple testing, with 20 metabolites having P-values between 2.1 × 10 and 4.0 × 10. Three metabolites (uridine, C-glycosyl tryptophan, and N-acetyl glycine) were statistically independent and thought to exert a direct effect on FI. Epiandrosterone sulphate, previously shown to be highly inversely associated with CWP, was found to exert an indirect influence on FI. Bioinformatics analysis of genome-wide association study and EWAS showed that FI and its covariation with CWP was through genomic regions involved in neurological pathways. Neurological pathway involvement accounts for the associated conditions of aging CWP and FI.

Shared genetic influence on frailty and chronic widespread pain: a study from TwinsUK.

Introduction: frailty is an increased vulnerability to adverse health outcomes, across multiple physiological systems, with both environmental and genetic drivers. The two most commonly used measures are Rockwood's frailty index (FI) and Fried's frailty phenotype (FP). Material and methods: the present study included 3626 individuals from the TwinsUK Adult Twin Registry. We used the classical twin model to determine whether FI and FP share the same latent aetiological factors. We also investigated the relationship between frailty and chronic widespread musculoskeletal pain (CWP), another holistic age-related condition with significant clinical impact. Results: FP and FI shared underlying genetic and environmental aetiology. CWP was associated with both frailty measures, and health deficits appeared to mediate the relationship between phenotypic frailty and pain. Latent genetic factors underpinning CWP were shared with frailty. While frailty was increased in the twins reporting pain, co-twin regression analysis indicated that the relationship between CWP and frailty is reduced after accounting for shared genetic and environmental factors. Conclusions: both measures of frailty tap the same root causes, thus this work helps unify frailty research. We confirmed a strong association between CWP and frailty, and showed a large and significant shared genetic aetiology of both phenomena. Our findings argue against pain being a significant causative factor in the development of frailty, favouring common causation. This study highlights the need to manage CWP in frail individuals and undertake a Comprehensive Geriatric Assessment in individuals presenting with CWP. Finally, the search for genetic factors underpinning CWP and frailty could be aided by integrating measures of pain and frailty.

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

A correction to this article has been published and is linked from the HTML version of this article.

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 × 10-8) or suggestively genome wide (p < 2.3 × 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.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Genome-wide methylation analysis of a large population sample shows neurological pathways involvement in chronic widespread musculoskeletal pain.

Chronic widespread musculoskeletal pain (CWP), has a considerable heritable component, which remains to be explained. Epigenetic factors may contribute to and account for some of the heritability estimate. We analysed epigenome-wide methylation using MeDIPseq in whole blood DNA from 1708 monozygotic and dizygotic Caucasian twins having CWP prevalence of 19.9%. Longitudinally stable methylation bins (lsBINs), were established by testing repeated measurements conducted ≥3 years apart, n = 292. DNA methylation variation at lsBINs was tested for association with CWP in a discovery set of 50 monozygotic twin pairs discordant for CWP, and in an independent dataset (n = 1608 twins), and the results from the 2 samples were combined using Fisher method. Functional interpretation of the most associated signals was based on functional genomic annotations, gene ontology, and pathway analyses. Of 723,029 signals identified as lsBINs, 26,399 lsBINs demonstrated the same direction of association in both discovery and replication datasets at nominal significance (P ≤ 0.05). In the combined analysis across 1708 individuals, whereas no lsBINs showed genome-wide significance (P < 10-8), 24 signals reached p≤9E-5, and these included association signals mapping in or near to IL17A, ADIPOR2, and TNFRSF13B. Bioinformatics analyses of the associated methylation bins showed enrichment for neurological pathways in CWP. We estimate that the variance explained by epigenetic factors in CWP is 6%. This, the largest study to date of DNA methylation in CWP, points towards epigenetic modification of neurological pathways in CWP and provides proof of principle of this method in teasing apart the complex risk factors for CWP.

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 United Kingdom twins (monozygotic [MZ] and dizygotic [DZ]), 297 of which were repeatedly measured participated in the study. MAIN OUTCOME MEASURE: Appendicular lean mass assessed using dual-energy X-ray absorptiometry technology, and methylated DNA immunoprecipitation sequencing 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 h(2) = 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 < .01 and Rrepeated > 0.40) were subjected to replication in the sample of 1196 individuals. Seven SMM methylation association signals replicated at a false discovery rate less than 0.1, and these were located in or near genes DNAH12, CAND1, CYP4F29P, and 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 SMM. Four replicated signals were related to genes with potential muscle functions, suggesting that the methylome of whole blood may be informative of SMM variation.

Genomics and metabolomics of muscular mass in a community-based sample of UK females.

The contribution of specific molecular-genetic factors to muscle mass variation and sarcopenia remains largely unknown. To identify endogenous molecules and specific genetic factors associated with appendicular lean mass (APLM) in the general population, cross-sectional data from the TwinsUK Adult Twin Registry were used. Non-targeted mass spec-based metabolomic profiling was performed on plasma of 3953 females (mostly dizygotic and monozygotic twins). APLM was measured using dual-energy X-ray absorptiometry (DXA) and genotyping was genome-wide (GWAS). Specific metabolites were used as intermediate phenotypes in the identification of single-nucleotide polymorphisms associated with APLM using GWAS. In all, 162 metabolites were found significantly correlated with APLM, and explained 17.4% of its variation. However, the top three of them (unidentified substance X12063, urate, and mannose) explained 11.1% (P ≤ 9.25 × 10(-26)) so each was subjected to GWAS. Each metabolite showed highly significant (P ≤ 9.28 × 10(-46)) associations with genetic variants in the corresponding genomic regions. Mendelian randomization using these SNPs found no evidence for a direct causal effect of these metabolites on APLM. However, using a new software platform for bivariate analysis we showed that shared genetic factors contribute significantly (P ≤ 4.31 × 10(-43)) to variance in both the metabolites and APLM--independent of the effect of the associated SNPs. There are several metabolites, having a clear pattern of genetic inheritance, which are highly significantly associated with APLM and may provide a cheap and readily accessible biomarker of muscle mass. However, the mechanism by which the genetic factor influences muscle mass remains to be discovered.

An omics investigation into chronic widespread musculoskeletal pain reveals epiandrosterone sulfate as a potential biomarker.

Chronic widespread musculoskeletal pain (CWP) is common, having a population prevalence of 10%. This study aimed to define the biological basis of the CWP/body mass association by using a systems biology approach. Adult female twins (n = 2444) from the TwinsUK registry who had extensive clinical, anthropometric, and "omic" data were included. Nontargeted metabolomics screening including 324 metabolites was carried out for CWP and body composition using dual-energy X-ray absorptiometry. The biological basis of these associations was explored through a genome-wide association study and replicated in an independent population sample (Cooperative Health Research in the Region of Augsburg [KORA] study, n = 2483). A causal role for the genetic variants identified was sought in CWP using a Mendelian randomisation study design. Fat mass/height2 was the body composition variable most strongly associated with CWP (TwinsUK: P = 2.4 × 10(-15) and KORA: P = 1.59 × 10(-10)). Of 324 metabolites examined, epiandrosterone sulfate (EAS) was highly associated with both CWP (P = 1.05 × 10(-09) in TwinsUK and P = 3.70 × 10(-06) in KORA) and fat mass/height2. Genome-wide association study of EAS identified imputed single nucleotide polymorphism rs1581492 at 7q22.1 to be strikingly associated with EAS levels (P ≤ 2.49 × 10(-78)), and this result was replicated in KORA (P = 2.12 × 10(-9)). Mendelian randomization by rs1581492 genotype showed that EAS is unlikely to be causally related to CWP. Using an agnostic omics approach to focus on the association of CWP with body mass index, we have confirmed a steroid hormone association and identified a genetic variant upstream of the CYP genes, which likely controls this response. This study suggests that steroid hormone abnormalities result from pain rather than causing it, and EAS may provide a biomarker that identifies subgroups at risk of CWP.

Environmental rather than genetic factors determine the variation in the age of the infancy to childhood transition: a twins study.

OBJECTIVE: Using a twins study, we sought to assess the contribution of genetic against environmental factor as they affect the age at transition from infancy to childhood (ICT). STUDY DESIGN: The subjects were 56 pairs of monozygotic twins, 106 pairs of dizygotic twins, and 106 pairs of regular siblings (SBs), for a total of 536 children. Their ICT was determined, and a variance component analysis was implemented to estimate components of the familial variance, with simultaneous adjustment for potential covariates. RESULTS: We found substantial contribution of the common environment shared by all types of SBs that explained 27.7% of the total variance in ICT, whereas the common twin environment explained 9.2% of the variance, gestational age 3.5%, and birth weight 1.8%. In addition, 8.7% was attributable to sex difference, but we found no detectable contribution of genetic factors to inter-individual variation in ICT age. CONCLUSIONS: Developmental plasticity impacts much of human growth. Here we show that of the ∼50% of the variance provided to adult height by the ICT, 42.2% is attributable to adaptive cues represented by shared twin and SB environment, with no detectable genetic involvement.

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).

Association of interleukin-6 gene polymorphisms with hand osteoarthritis and hand osteoporosis.

OBJECTIVE: Several genes, including IL-6 encoding pro-inflammatory cytokines, are involved in development of osteoarthritis and osteoporosis. The association of radiographic hand osteoarthritis (RHOA) and osteoporosis related phenotypes (RHOP) with polymorphisms in IL-6 has been reported inconsistently. The aim of this study was to examine the association, between RHOA and RHOP and IL-6 polymorphisms in two independent samples. METHODS: Two samples: UK females, including 1440 individuals assessed for RHOA and 3470 assessed for RHOP; Chuvash pedigree including 1499 females and males were assessed for RHOP and RHOA. SNPs were genotyped in the IL-6 genomic region, and used in association analysis with RHOA and RHOP phenotypes. RESULTS: RHOP phenotypes showed similar heritability estimates in both samples, ranging from 34.5 ± 5.5% to 61.0 ± 2.4%. RHOA in Chuvash had substantially lower heritability estimates compared to twins (e.g. OSP scores: 11.8 ± 2.3% vs. 39.2 ± 4.1%) with much higher prevalence and considerably stronger correlation with age (r = 0.811 vs. r = 0.505). RHOA in Chuvash sample may be traumatic in nature, caused by heavy and prolonged manual work related to their private farming. There were a number of statistically significant association results with both types of phenotypes. The most consistent result was obtained for JSN in both samples with SNP from the same haploblock. Their combined probability of no association was only p = 0.000003. Additionally, there were SNPs common for both RHOA and RHOP. CONCLUSIONS: We have shown polymorphisms in IL_6 are significantly associated with RHOA and hand RHOP in two samples having different ethnicity and lifestyle. Age × environment × genes interaction appears as an important factor of RHOA manifestation and progression.

Low back and common widespread pain share common genetic determinants.

Low back (LBP) and chronic widespread musculoskeletal pain (CWP) both have a significant genetic component and are associated with increased body mass index (BMI). We examined whether LBP and CWP share common genetic factors, and to what extent this correlation is modified by the genetic factors influencing BMI. Genetic analysis of binary traits such as pain is not simple, particularly if their risk is associated with age or other quantitative traits. Implementing Falconer's polygenic threshold concept for dichotomous traits inheritance, we developed new software to examine the extent of the genetic influence on LBP and CWP under age and BMI dependence. The analysis was conducted on 3266 and 2256 UK female twins, assessed for LBP and CWP, respectively. Analysis of the liability scores with threshold to LBP and CWP established substantial contribution of genetic factors to their variation (h(2) > 0.60, p<0.004-0.0003) and covariation (p=3.1E-08). Some 39% of the CWP and 70% of the LBP heritability estimates were attributable to genetic effects shared by both phenotypes, and 40% and 67% of the residual variation is caused by environmental factors simultaneously affecting both pain syndromes. However, contribution of BMI to variation/covariation of both pain phenotypes-although statistically highly significant (p∼10-7)-was not determinative.

Assessment of age-related changes in heritability and IGF-1 gene effect on circulating IGF-1 levels.

It is well established that insulin-like growth factor 1 (IGF-1) circulating levels correlate with age and that heritability and influence of IGF-1 gene variation on IGF-1 levels also well-known. However, the influence of age on the genetic factors determining IGF-1 levels is not clear. In this study, we compared heritability estimates between younger (<52 years) and older (>52 years) twins and tested: (a) whether single nucleotide polymorphisms (SNPs) lying within 100 kbp of the IGF-1 gene are also associated with IGF-1 variation and (b) whether associated SNPs show interaction with age on IGF-1 levels. To achieve these aims, we measured plasma levels of IGF-1 and genotyped 18 SNPs with minor allele frequency >0.1 in a large sample, 4,471 UK female twins. Heritability explained 42 % of IGF-1 variation adjusted for age and in unadjusted sample was independent of age. Ten SNPs in four haploblocks showed significant association with IGF-1 levels, with p = 0.01-0.0005. The most distal SNP was located up to 90 kbp from the IGF-1 gene. When their age-dependent effects were examined, one SNP, rs855203, showed significant (p = 0.0009) age-dependent interaction effect on IGF-1 levels variation. This is the first study to test the age × genotype interaction in IGF-1 levels. The genomic region marked by rs855203 may consequently be of significance for further molecular and pharmacogenetic research, in particular in advanced age.

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 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 findings. The present results are similar with the earlier results of finger ridge count diversity in twin data, which suggested that finger ridge count diversity is under genetic control.

Inheritance of dermatoglyphic asymmetry in 500 Indian pedigrees: complex segregation analysis.

The major aim of this study is to determine the mode of inheritance of asymmetry of quantitative dermatoglyphic traits based on principal factors through the application of complex segregation (genetic model fitting) analyses on a large ethnically homogeneous sample of 500 Indian pedigrees (2435 individuals) of two generations. By segregation analysis of the traits- PC1_FA both Mendelian and Environmental models were rejected (< 0.001) with the General model, i.e. that despite presence of significant inheritance (rejection of Environmental model), the nature of inheritance is more complex, than Mendelian one. Although a little genetic effect was observed due to familial correlations on asymmetry traits, no evidence was found of major gene contribution to be involved, but this does not contradict the notion postulated by several earlier authors that asymmetry (fluctuating) provides a measure of developmental instability in human.