Research on genetic model of keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of genetic factors on the pathogenesis of keratoconus and its genetic model.METHODS: Genetic epidemiological methods were used to investigate the prevalence of keratoconus in 280 first-degree relatives of 100 patients with keratoconus who attended Henan Eye Hospital between July 2020 and April 2023. The heritability was estimated by Falconer regression method. The general genetic model was calculated using Penrose method, and the genetic model was confirmed by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory.RESULTS: The results showed that there were 16(5.714%)first-degree relatives of keratoconus probands suffering from keratoconus, and the heritability of keratoconus was(86.100±7.400)%. The S/q score calculated by the Penrose method was 35.348, which was near to 1/(q)1/2, suggesting that the genetic model of keratoconus might be polygenic inheritance. The expected prevalence in first-degree relatives of keratoconus patients by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory were 5.900%, 7.714% and 5.700%, respectively, which showed no significant differences from the actual prevalence(5.714%), suggesting that keratoconus was a polygenetic disease.CONCLUSION:Genetic factors might play an important role in the pathogenesis of keratoconus, and keratoconus is a polygenetic disease.

New progress on the pathogenesis research of primary angle-closure glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#Primary angle-closure glaucoma(PACG)is the most common type of glaucoma in clinical. It is characterized by progressive and irreversible development with high global incidence and high possibility of blindness. The pathogenesis of PACG is complicated. It is not only associated with the abnormality of the ocular anatomy, such as the small cornea, short eye axis and shallow anterior chamber, but also found that the abnormality of the lens, iris, ciliary body and choroid are related to the pathogenesis of PACG in recent years. Moreover, the occurrence of PACG is also closely related to genetic and psychological stress factors. Our study summarized some literatures and made a brief discussion on the pathogenesis of PACG from the three aspects of anatomical characteristics, genetic factors, and psychological stress. We hope to provide useful theoretical support for the early diagnosis and treatment of glaucoma.

High levels of chemerin associated with variants in the NOS3 and APOB genes in rural populations of Ouro Preto, Minas Gerais, Brazil

Chemerin is an adipokine that has been associated with components of metabolic syndrome. It has been described to affect adipocyte metabolism and inflammatory responses in adipose tissue, as well as the systemic metabolism of lipids and glucose. Few epidemiological studies have evaluated classical and genetics cardiovascular risk factors (CVRFs) in the mixed adult rural population in Brazil. Therefore, the present study explored possible associations between CVRFs and chemerin. This cross-sectional study included 508 adults from the rural localities of Lavras Novas, Chapada, and Santo Antônio do Salto in Ouro Preto, Minas Gerais, Southeast Brazil. Demographic, behavioral, clinical, biochemical, anthropometric variables, and 12 single nucleotide polymorphisms (SNPs) linked with metabolic syndrome phenotypes were evaluated for associations with chemerin level. There was a significant association of high triglyceride levels [odds ratio (OR)=1.91, 95%CI: 1.23−2.98], insulin resistance (OR=1.82, 95%CI: 1.03−3.22), age (OR=1.64, 95%CI: 1.08−2.49), and sex (OR=1.99, 95%CI: 1.35−2.95) with high levels of chemerin. High chemerin levels were significantly associated with the genetic polymorphisms rs693 in the APOB gene (OR=1.50, 95%CI: 1.03−2.19) and rs1799983 in the NOS3 gene (OR=1.46, 95%CI: 1.01−2.12) for the AA and GT+TT genotypes, respectively. In the concomitant presence of genotypes AA of rs693 and GT+TT of rs1799983, the chance of presenting high levels of chemerin showed a 2.21-fold increase (95%CI: 1.25−3.88) compared to the reference genotype. The development of classical CVRFs in this population may be influenced by chemerin and by two risk genotypes characteristic of variants in well-studied genes for hypertension and dyslipidemia.

Familial aggregation and heritability of markers of metabolic risk, physical activity, and physical fitness in nuclear families from Muzambinho (Minas Gerais, Brazil)

ABSTRACT Objective This study investigated the familial aggregation and heritability of markers of metabolic risk, physical activity, and physical fitness in nuclear families from Muzambinho (Minas Gerais, Brazil). Subjects and methods The study included members of 139 families, comprising 97 fathers (aged 40 ± 7 years), 129 mothers (35 ± 6 years), 136 sons (12 ± 4 years), and 121 daughters (12 ± 5 years). Evaluated markers included (A) body mass index, waist circumference, glycemia, and cholesterolemia, as metabolic risk markers; (B) total weekly volume of physical activity, as a physical activity marker; and (C) relative muscle strength, as a physical fitness marker. Correlations between family members and heritability (h2) were estimated using the software S.A.G.E. Results Significant familial correlations were obtained between parents-offspring for glycemia and cholesterolemia (both ρ = 0.21, p < 0.05) and relative muscle strength (ρ = 0.23, p < 0.05), and between siblings for waist circumference, glycemia, total weekly volume of physical activity, and relative muscle strength (ρ variation 0.25 to 0.36, p < 0.05). Heritability values were significant for almost all variables (h2 variations: 20% to 57% for metabolic risk markers, 22% for the total weekly volume of physical activity, and 50% for relative muscle strength), except for waist circumference (h2 = 15%, p = 0.059). Conclusion The presence of significant correlations between family members and/or significant heritability strengthens the possible genetic and/or common familial environment influence on metabolic risk markers, total weekly volume of physical activity, and relative muscle strength.

Mendelian Randomization Analysis in Observational Epidemiology

Mendelian randomization (MR) in epidemiology is the use of genetic variants as instrumental variables (IVs) in non-experimental design to make causality of a modifiable exposure on an outcome or disease. It assesses the causal effect between risk factor and a clinical outcome. The main reason to approach MR is to avoid the problem of residual confounding. There is no association between the genotype of early pregnancy and the disease, and the genotype of an individual cannot be changed. For this reason, it results with randomly assigned case-control studies can be set by regressing the measurements. IVs in MR are used genetic variants for estimating the causality. Usually an outcome is a disease and an exposure is risk factor, intermediate phenotype which may be a biomarker. The choice of the genetic variable as IV (Z) is essential to a successful in MR analysis. MR is named ‘Mendelian deconfounding’ as it gives to estimate of the causality free from biases due to confounding (C). To estimate unbiased estimation of the causality of the exposure (X) on the clinically relevant outcome (Y), Z has the 3 core assumptions (A1-A3). A1) Z is independent of C; A2) Z is associated with X; and A3) Z is independent of Y given X and C; The purpose of this review provides an overview of the MR analysis and is to explain that using an IV is proposed as an alternative statistical method to estimate causal effect of exposure and outcome under controlling for a confounder.

Polymorphisms in the TGFB1 and IL2RA genes are associated with clinical forms of leprosy in Brazilian population

BACKGROUND Leprosy is a chronic infectious disease caused by Mycobacterium leprae, and compromises the skin and peripheral nerves. This disease has been classified as multibacillary (MB) or paucibacillary (PB) depending on the host immune response. Genetic epidemiology studies in leprosy have shown the influence of human genetic components on the disease outcomes. OBJECTIVES We conducted an association study for IL2RA and TGFB1 genes with clinical forms of leprosy based on two case-control samples. These genes encode important molecules for the immunosuppressive activity of Treg cells and present differential expressions according to the clinical forms of leprosy. Furthermore, IL2RA is a positional candidate gene because it is located near the 10p13 chromosome region, presenting a linkage peak for PB leprosy. METHODS A total of 885 leprosy cases were included in the study; 406 cases from Rondonópolis County (start population), a hyperendemic region for leprosy in Brazil, and 479 cases from São Paulo state (replication population), which has lower epidemiological indexes for the disease. We tested 11 polymorphisms in the IL2RA gene and the missense variant rs1800470 in the TGFB1 gene. FINDINGS The AA genotype of rs2386841 in IL2RA was associated with the PB form in the start population. The AA genotype of rs1800470 in TGFB1 was associated with the MB form in the start population, and this association was confirmed for the replication population. MAIN CONCLUSIONS We demonstrated, for the first time, an association data with the PB form for a gene located on chromosome 10. In addition, we reported the association of TGFB1 gene with the MB form. Our results place these genes as candidates for validation and replication studies in leprosy polarisation.

СОНСГОЛЫН ХҮНД ХЭЛБЭРИЙН БУУРАЛТТАЙ ХҮНД CONNEXIN 26 ГЕНИЙН МУТАЦИЙГ ТОДОРХОЙЛСОН ТӨСӨЛТ АЖЛЫН ЗАРИМ ҮР ДҮН / Шинэ санаа Шинэ нээлт

@#BACKGROUND. Sensorineural hearing impairment (SNHI) is the most common inherited sensory defect, affecting about 3 per 1000 children. More than 50% of these patients have a genetic cause (i.e. hereditary hearing impairment; HHI). Mutations in certain genes were noted to be extraordinarily popular in the deaf patients across different populations, making molecular screening feasible for these common deafness genes. One of the most important characteristics that we have learned concerning hereditary hearing loss is that common deafness genes and their mutations are usually different according to the ethnic background. As demonstrated in our previous studies performed in Taiwanese patients, the mutation spectrums of common deafness genes, such as the GJB2 gene and the SLC26A4 gene, are different from those in the Caucasian or even other Asian populations. These findings further underscore the indispensability of the collection of local data in terms of genetic counseling. In the collaborative project, we have successfully established a cohort of >100 hearingimpaired families, and clarified the genetic epidemiology of deafness in the Mongolian population. We identified several special deafness mutations such as GJB2 c.23+1G>A, c.559_604dup, and SLC26A4 c.919-2A>G, and our results revealed that Mongolian patients demonstrate a unique genetic profile in deafness as compared to other East Asian populations (paper in preparation). Meanwhile, by organizing a seminar at National Taiwan University Hospital in March 2017, we have transferred crucial concepts and techniques regarding how to perform genetic testing for deafness to the Mongolian colleagues. In the future, we plan to strengthen the mutual collaboration by expanding the clinical cohort and upgrading the genetic examination platform using the NGS techniques.

A review of genetic epidemiology of personality disorder / 中国心理卫生杂志

This article reviews studies on the heredity of personality disorders and family environment factors from the population-based studies, and summarizes the interaction between genetic factors and environmental factors. Studies have shown that there is a genetic basis for personality disorders, including family studies, twin studies, and neurophysiological studies. In addition, environmental factors, including social psychological factors, also play an important role in the development of personality disorder. In sum, the occurrence of personality disorder is the result of interactions between genetic factors and environmental factors. This paper snmmarizes sresearch on personality disorders, and investigates the role of interaction between genetic and environmental factors in the development of personality disorders. Such evidence has implications for effective prevention and intervention of personality disorders.

МОНГОЛ ХҮНИЙ ТӨРӨЛХИЙН БОЛОН ОЛДМОЛ ХЭЛБЭРИЙН ДҮЛИЙН ҮЕИЙН CONNEXIN 26 ГЕНИЙН МУТАЦИЙГ ТОДОРХОЙЛСОН СУДАЛГААНЫ АЖЛЫН ЗАРИМ ҮР ДҮН / Шинэ санаа Шинэ нээлт

@#BACKGROUND. Sensorineural hearing impairment (SNHI) is the most common inherited sensory defect, affecting about 3 per 1000 children. More than 50% of these patients have a genetic cause (i.e. hereditary hearing impairment; HHI). Mutations in certain genes were noted to be extraordinarily popular in the deaf patients across different populations, making molecular screening feasible for these common deafness genes. One of the most important characteristics that we have learned concerning hereditary hearing loss is that common deafness genes and their mutations are usually different according to the ethnic background. As demonstrated in our previous studies performed in Taiwanese patients, the mutation spectrums of common deafness genes, such as the GJB2 gene and the SLC26A4 gene, are different from those in the Caucasian or even other Asian populations. These findings further underscore the indispensability of the collection of local data in terms of genetic counseling. In the collaborative project, we have successfully established a cohort of >100 hearing-impaired families, and clarified the genetic epidemiology of deafness in the Mongolian population. We identified several special deafness mutations such as GJB2 c.23+1G>A, c.559_604dup, and SLC26A4 c.919-2A>G, and our results revealed that Mongolian patients demonstrate a unique genetic profile in deafness as compared to other East Asian populations (paper in preparation). Meanwhile, by organizing a seminar at National Taiwan University Hospital in March 2017, we have transferred crucial concepts and techniques regarding how to perform genetic testing for deafness to the Mongolian colleagues. In the future, we plan to strengthen the mutual collaboration by expanding the clinical cohort and upgrading the genetic examination platform using the NGS techniques.

Recharacterization of Morphological and Genetic Feature of Getah Virus Isolated from South Korea

Three QIAG93 strains, QIAG9301, QIAG9302 and QIAG9303 that have been identified as Getah virus (GETV) are analyzed in this study. The morphological features of three virus isolates were observed by using electron microscopy, suggesting that the QIAG9301, QIAG9302 and QIAG9303 isolate can be classified as tentative member of Alphavirus species in the Semliki Forest complex. The full length of the structural polyprotein gene of each QIAG93 isolate (QIAG9301, QIAG9302 and QIAG9303) was determined that are identical in size, comprising 3759 nucleotides that encoded 1253 amino acids. The sequence analysis of the structural polyprotein gene, including the C, E3, E1, 6K and E2 domain, showed that each QIAG93 isolate shares >98.9% sequence identity. The phylogenetic analysis and evolutionary distance (ED) estimation based on the structural polyprotein gene sequence showed that the QIAG9301 isolate is closely related to GETV South Korea strain (99.9% sequence identity and ED value 0.001) and Chinese GETV YN0540 strain (99.3% sequence identity ED value 0.007) than other Alphavirus species analyzed in this study. Both QIAG9032 and QIAG9303 isolate exhibited genetically close relationship with Mongolian GETV LEIV17741MPR strain (at least 99.3% sequence identity and mean ED value 0.0065). Therefore, our findings will be valuable for molecular epidemiological analyses of GETV in Korea and contribute to a further study on pathogenicity of three QIAG93 isolates in animals.

Nuclear-cytoplasmic interaction QTL mapping of the lipoprotein and cholesterol traits in mice / 中国比较医学杂志

Objective To study the cholesterol nuclear-cytoplasmic interaction effect and position cholesterol traits QTL in mice.Methods Improving the nuclear-cytoplasmic interaction models and methods that have been constructed, and analyzing the public database of total cholesterol and lipoprotein data of F2 group that derived from DBA/2J ( D2) and CAST/EiJ ( CAST) mice.Results Six QTL that controlling total cholesterol, HDL and nonHDL were located in 4 linkage groups in the genome.In the models constructed in this study, we found a QTL has significant interaction with cytoplasmic background, which changes the previous results of data analysis, the genetic mouse cholesterol and lipoprotein components opened up new ideas.Conclusion Mouse cholesterol trait is the result of interaction of nuclear genes and cytoplasmic background.

The impact of lipid-metabolizing genetic polymorphisms on body mass index and their interactions with soybean food intake: a study in a Chinese population / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index (BMI), and estimate their interactions with soybean food intake.</p><p><b>METHODS</b>A community-based cross-sectional survey was conducted in a Chinese Han population. BMI, soybean food intake, and single nucleotide polymorphisms of rs599839, rs3846662, rs3846663, rs12916, rs174547, rs174570, rs4938303, and rs1558861 were measured in 944 subjects. A multivariate logistic regression was used to analyze the association of the studied polymorphisms with BMIs. The expectation-maximization algorithm was employed to evaluate the extent of linkage disequilibrium between pairwise polymorphisms. The gene-environment interaction was assessed in the general multifactor dimensionality reduction model.</p><p><b>RESULTS</b>The polymorphisms of rs3846662 and rs3846663 were associated with 10% highest BMIs when comparing to the 10% lowest values both in individuals and haplotype-based association tests. Although no statistically significant gene-environment interactions were found, people with the haplotype composed of C allele in rs3846662 and T allele in rs3846663 and low frequency of soybean intake had significantly higher risk to overweight and obesity as compared with those with the haplotype consisting of T allele in rs3846662 and C allele in rs3846663 and highly frequent soybean food intake, with an odds ratio of 1.64 (95% confidence interval: 1.15-2.34, P<0.01) after adjusting for the common confounders.</p><p><b>CONCLUSION</b>Our study has suggested that rs3846662 and rs3846663 may be the potential candidate polymorphisms for obesity, and their effect on the pathogenesis could be mediated by the frequency of soybean food intake.</p>

Genetic and environmental influences on blood pressure and physical activity: a study of nuclear families from Muzambinho, Brazil

Blood pressure (BP) and physical activity (PA) levels are inversely associated. Since genetic factors account for the observed variation in each of these traits, it is possible that part of their association may be related to common genetic and/or environmental influences. Thus, this study was designed to estimate the genetic and environmental correlations of BP and PA phenotypes in nuclear families from Muzambinho, Brazil. Families including 236 offspring (6 to 24 years) and their 82 fathers and 122 mothers (24 to 65 years) were evaluated. BP was measured, and total PA (TPA) was assessed by an interview (commuting, occupational, leisure time, and school time PA). Quantitative genetic modeling was used to estimate maximal heritability (h²), and genetic and environmental correlations. Heritability was significant for all phenotypes (systolic BP: h² = 0.37 ± 0.10, P < 0.05; diastolic BP: h² = 0.39 ± 0.09, P < 0.05; TPA: h² = 0.24 ± 0.09, P < 0.05). Significant genetic (r g) and environmental (r e) correlations were detected between systolic and diastolic BP (r g = 0.67 ± 0.12 and r e = 0.48 ± 0.08, P < 0.05). Genetic correlations between BP and TPA were not significant, while a tendency to an environmental cross-trait correlation was found between diastolic BP and TPA (r e = -0.18 ± 0.09, P = 0.057). In conclusion, BP and PA are under genetic influences. Systolic and diastolic BP share common genes and environmental influences. Diastolic BP and TPA are probably under similar environmental influences.

Molecular epidemiology of β-thalassemia in Pakistan: Far reaching implications.

Background: β -Thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing β-thalassemia. Aim: To achieve this objective, Identification of the spectrum of genetic mutations, especially for various ethnic backgrounds in Pakistan. Therefore, we designed a cross sectional prospective study to identify the frequency of various gene mutations in different ethnic groups of Pakistan. Materials and Methods: Over a 5-year period, DNA from 648 blood samples {including specimens of chorionic villus sampling (CVS)} were analyzed for the twelve most common β-thalassemia mutations found in the Pakistani population by a Multiplex amplification refractory mutation system (ARMS). Each sample was analyzed for the mutation as well as the normal gene, appropriate with negative and positive controls, and reagent blanks. Results: Out of 648 samples mutations were identified in 640 (98.75%) samples by multiplex ARMS. 8 common β-thalassemia mutations were identified in 8 different ethnic groups accounting for 93.9% of the β-thalasemia alleles. Conclusions: Based on the outcome of this study a cost effective proposal is formulated for detection of β-thalassemia mutations.

Agregação familiar na adiposidade do tronco: um estudo em famílias nucleares portuguesas / Familial aggregation on trunkal fat: a study with Portuguese families

Este estudo teve como objetivos: 1) identificar a presença indireta de transmissão vertical de fatores genéticos entre progenitores e descendentes em dois fenótipos da adiposidade do tronco (AT); 2) estimar a contribuição dos fatores genéticos e ambientais responsáveis pela variabilidade fenotípica da adiposidade do tronco relativa (ATrel) e absoluta (ATabs) em termos populacionais. A amostra foi constituída por 422 indivíduos pertencentes a 107 famílias nucleares portuguesas. Os fenótipos da AT foram avaliados com um aparelho de BIA da marca Tanita® modelo BC- 418MA. A estrutura familiar e a análise do comportamento genérico das variáveis entre diferentes membros familiares foram realizadas no "software" PEDSTATS. Para calcular a correlação entre familiares foi utilizado o módulo FCOR do "software" de Epidemiologia Genética S.A.G.E 5.3. As estimativas de heritabilidade (h²) foram realizadas através do método de verossimilhança implementado no "software" SOLAR. Os valores dos coeficientes de correlação entre os diferentes graus de parentesco foram baixos a moderados para ATrel (0,205 < r < 0,738) e ATabs (0,199 < r < 0,782). Os fatores genéticos explicaram 50 e 47 por cento da variação dos fenótipos da ATrel e ATabs, respectivamente. Esses resultados: 1) indicam uma forte agregação familiar na AT de famílias nucleares portuguesas; 2) contribuem para estudos avançados de Epidemiologia Genética e 3) ressaltam a necessidade da implementação de intervenções físicas e nutricionais direcionadas a toda família.

The aims of this study was to 1) identify the presence of indirect transmission of genetic factors between parents and children in two phenotypes of trunk fat, and 2) estimate the contribution of genetic and environmental factors responsible for phenotypic variation on relative trunk fat and absolute trunk fat. The sample consisted of 422 individuals from 107 Portuguese nuclear families. Trunk fat phenotypes were measured with a bioelectric impedance device Tanita ® model BC-418MA. Family structure and analysis of the generic behavior of the variables between different family members were verified in PEDSTATS software. Familiar correlations were computed in the FCOR module of SAGE 5.3 software. Heritability estimates (h²) were performed using the likelihood method implemented in SOLAR software. Correlation coefficients between relatives were low to moderate on relative trunk fat (0.205 < r < 0.738) and absolute trunk fat (0.199 < r < 0.782). Genetic factors explained 50 and 47 percent of the variation in phenotypes of relative and absolute trunk fat, respectively. These results 1) indicate a strong familial aggregation on trunk fat of Portuguese nuclear families, 2) contribute to advanced studies in Genetic Epidemiology 3) and emphasize the need for physical and nutritional interventions directed to all family members.

Fatores genéticos e ambientais da atividade física. Um estudo em famílias com três gerações / Physical activity level of three generation families. Genetic and environmental factors

Os objetivos do estudo foram: (1) verificar a presença indireta de transmissãovertical de fatores genéticos nos níveis de atividade física (AF) e comportamento sedentário (CS) ao longo de três gerações e (2) estimar a magnitude dos fatores genéticos e ambientais. A amostra foi constituída por 1034 indivíduos de 100 famílias, com três gerações, provenientes da região de Lisboa, Portugal. A avaliação da AF e CS foi realizada por meiodo IPAQ, forma curta. Os fenótipos avaliados foram: atividade física total (AFT); vigorosa (AFV); moderada (AFM); caminhada; tempo sentado (TS), tempo a ver televisão (TTV) e classificação do nível de AF. Calculou-se o índice de massa corporal (IMC). A estrutura familiar e o comportamento genérico das variáveis entre familiares foram analisados nosoftware Pedstats. A heritabilidade (h2) e o efeito do ambiente partilhado foram estimados pelo método de máxima verossimilhança implementado no software Solar. A representação gráfica foi feita no software HLM. Ajustou-se os resultados às covariáveis: sexo, idade, sexo*idade, idade2, sexo*idade2 e IMC. Foi adotado um nível de significância de 0,05. Asestimativas de h2 foram as seguintes: AFV h2=0,35±0,06 (p<0.0001); AFM h2=0,29±0,06 (p<0.0001); caminhada h2=0,40±0,06 (p<0.0001); AFT h2=0,28±0,06; TS h2=0,29±0,06 (p<0.0001); TTV h2=0,15±0,06 (p<0.003) e determinação do nível de AF h2=0,35±0,14 (p<0.007). O efeito ambiental partilhado não foi significativo. Os resultados indicam que os fatores genéticos podem contribuir entre 15 a 40% da variabilidade total nos diferentes fenótipos da AF e CS, considerada influência baixa a moderada. Fatores ambientais não-transmitidos correspondem à maior contribuição na determinação desses fenótipos.

This study aims (1) to investigate the presence of familial aggregation in physical activity (PA) levels and sedentary behavior (SB) among members of three generations families and (2) to estimate the magnitude of additive genetic influences on PA and SB phenotypes. The sample consisted of 100 extended families covering three generations (n=1034), from the Lisbon area, Portugal. Phenotypes were assessed via the short version of the self-administered International Physical Activity Questionnaire (IPAQ-SF). Measured phenotypes: total physical activity (TPA); vigorous (VPA); moderate (MPA); walking; time spent in sitting time (ST), watching television (WT) and PA levels classification. Body mass index (BMI) was calculated.Exploratory family analysis in all phenotypes was conducted in PEDSTATS software. The genetic component (h2) and shared environmental effect were estimated using maximum likelihood implemented in the SOLAR software package. All graphs were done in HLM software. Sex, age, sex*age, age2, sex*age2 and BMI were used as covariates. Significant level was set at0,05. Genetic component estimates (h2) were as follows: TPA h2=0,28±0,06 (p<0.0001); VPA h2=0,35±0,06 (p<0.0001); MPA h2=0,29±0,06 (p<0.0001); walking h2=0,40±0,06 (p<0.0001); ST h2=0,29±0,06 (p<0.0001); WT h2=0,15±0,06 (p<0.003) and determination of the level physical activity h2=0,35±0,14 (p<0.007). Shared environmental effect was not significant.These results showed a low-to-moderate genetic contribution, between 15% to 40% of the total variability, in the PA and SB phenotypes. The genetic factors have low to moderate influence in this sample. Non-shared environmental factors appear to have the major contribution in these phenotypes.

Agregação familiar nos níveis de atividade física: um resumo do estado da arte / Familial aggregation in physical activity levels: a brief summary of the state of the art

Objetivo: Rever o estado atual do conhecimento sobre os efeitos genéticos na variabilidade dos níveis de atividade física, a partir de uma análise centrada em estudos agregação familiar, com base na Genética Quantitativa. Métodos: Realizou-se uma busca nas bases de dados Pubmed e Scopus, incluindo os estudos com base em delineamentos com famílias nucleares e/ou pedigrees extensos e estimativas de heritabilidade. Tais pesquisas deveriam apresentar questionários, acelerômetros e pedômetros como técnicas de avaliação dos níveis de atividade física, e a publicação deveria estar em formato de artigo ou relatório de pesquisa. Resultados: Presença de grande variabilidade inter e intra fenótipos sugerindo que os fatores genéticos são responsáveis por 6 a 62% da variação total dos níveis de atividade física, em muitos casos, com forte presença do envolvimento ambiental comum, partilhado pela família. A discrepância dos resultados pode ser condicionada por diferentes aspectos estruturais de cada pesquisa, bem como pela variabilidade dos instrumentos utilizados, dos fenótipos avaliados e das populações envolvidas. Conclusões: Os fenótipos da atividade física são complexos, de natureza poligênica e multifatorial. Os fatores genéticos são responsáveis por efeitos reduzidos a moderados da variabilidade desses fenótipos. Os dados relatados são significativos e constituem a base genética, ainda pouco explorada, para o desenvolvimento de pesquisas em Genética Molecular. Dessa forma, estabelecem um suporte relevante na definição de investigações e intervenções futuras no território da Epidemiologia Genética aplicada à atividade física.

Purpose: To present an up-to-date summary about genetic influences in physical activity (PA) variability based on familial aggregation studies within the realm of Quantitative Genetics. Methods: Pubmed and Scopus databases were searched for published papers and reports on nuclear families and/or extensive pedigrees where heritability estimates were computed, and PA levels were assessed by means of questionnaires, accelerometers and pedometers. Results: Wide variability between and within phenotypes suggesting that 6 to 62% of PA?s total variation was due to genetic factors as well as common environment shared by family members. Different structural aspects related to design of each study, as well as different methods for phenotypic assessment and sample may explain the many differences among results. Conclusion: PA phenotypes are complex, polygenic and multifactorial in their nature. Genetic factors are responsible for reduced-to-moderate phenotype variability. This data is relevant and is the genetic basis, still underexplored, for the development of Molecular Genetics research. In addition, future studies and interventions within the realm of Genetic Epidemiology applied to PA should start from this set of highly relevant information

Hardy-Weinberg equilibrium in genetic epidemiology / 中南大学学报(医学版)

Hardy-Weinberg equilibrium test is the base of genetic epidemiology. The new methods for Hardy-Weinberg equilibrium test involve: X chromosome-linked single nucleotide polymorphism Hardy-Weinberg test, inbreeding coefficient(F) test, an incomplete enumeration algorithm for an exact test of Hardy-Weinberg proportions with multiple alleles, and graphical tests for Hardy-Weinberg equilibrium based on the ternary plot. It is necessary to conduct Hardy-Weinberg equilibrium test in genetic epidemiology studies and adjust the associations as deviation of Hardy-Weinberg equilibrium occurs.

Fatores genéticos e variabilidade na pressão arterial: uma breve revisão da literatura / Genetic factors and variability in blood pressure: a brief literature review

O objetivo desta revisão foi abordar aspectos relacionados a importância dos fatores genéticos na variabilidade dos valores da pressão arterial. Foi realizada uma pesquisa na base de dados Pubmed e selecionados (1) estudos de agregação familiar com estimativas de heritabilidade, (2) estudos de linkage apenas com resultados significativos e (3) estudosde associação entre hipertensão arterial, genes candidatos e seus variantes alélicos, com base em delineamento de caso-controle. As estimativas de heritabilidade para a pressão arterial sistólica e diastólica variaram entre 14-68% e 6-62%, respectivamente. Foi verificadoa presença de linkage para a pressão arterial sistólica nos cromossomas 2, 5, 6, 15 e 17. Os principais genes candidatos apresentaram resultados díspares na associação com a hipertensão. Conclui-se que a pressão arterial é um fenótipo poligênico, onde os fatores genéticos governam uma parte moderada a substancial da magnitude de sua variabilidadenas populações. Os genes candidatos identificados não explicam de modo suficientemente satisfatório a hipertensão arterial.

The main purpose of this review was to gather relevant information regarding the importance of genetic factors for the variability of blood pressure levels. A search was performed in the Pubmed database, and the following studies were selected: (1) studies reporting familial aggregation with heritability estimates, (2) linkage studies reporting only significant results, and (3) association studies between blood pressure, candidate genes and their allelic variants using a case-control design. Heritability estimates for systolic and diastolic blood pressure ranged from 14to 68% and from 6 to 62%, respectively. We found significant linkage results for systolic blood pressure on chromosomes 2, 5, 6, 15 and 17. Relevant candidate genes presented disparate results in terms of their association with arterial hypertension. Blood pressure is a polygenic phenotype whose variation is partially mediated by genetic factors. The candidate genes identified do not sufficiently explain arterial hypertension.

Genetic epidemiological study on single nucleotide polymorphisms associated with hepatocellular carcinoma in patients with chronic HBV infection / 대한간학회지

Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV) as an etiologic agent in 80% of cases, and is the major cause of death among HBV carriers. Family history of HCC is a known risk factor for the development of HCC among chronically HBV infected patients; therefore, genetic factors are likely to modify the risk of HCC. However, the genetic factors that determine progression to HCC remain mostly to be recovered. It is estimated that there are millions of single nucleotide polymorphisms (SNPs) within human genome and they are likely to explain much of the genetic diversity of individuals. In this review, the natural history of HBV infection and host genetic factors related to HCC, study design and target gene selection for the detection of SNPs related to the occurrence of HCC were discussed. Also, several SNPs or haplotypes, which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection, were reviewed. Especially, recent studies in Korea, one of the HBV endemic areas, were discussed. Screening of these polymorphisms might be useful in clinical practice to stratify the lower or higher risk group for HCC and might modify the design of HCC surveillance programs in patients with chronic HBV infection, if further genetic susceptibilities are identified. The ongoing studies of the distributions and functions of the implicated allele polymorphisms will not only provide insight into the pathogenesis of HCC, but may also provide a novel rationale for new methods of diagnosis and therapeutic strategies.