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AbstractAlthough there is evidence that social status has a genetic basis, it is less known whether the genetic predisposition differs between men and women as well as among different status indicators and whether there are any intercorrelations among predispositions of status indicators. We therefore investigated the genetic predisposition for different indicators of social status separately for men and women, using polygenic scores obtained from the Wisconsin Longitudinal Study. We used multivariate polygenic regression of 7 different social status indicators on a total of 24 different polygenic scores. We find that in both men and women, wages and education show more associations with polygenic scores than the other status indicators. Also, the genetic predispositions for education and wages are correlated in both men and women, whereas in men more than in women, the genetic predispositions seem to cluster into wages and education on the one hand, and status indicators of position in the hierarchy, on the other hand, with being in a management position somewhere in between. These findings are consistent with an assumption of two different forms of selection pressure associated with either cognitive skill or dominance, which holds true particularly in men. We conclude that the genetic predisposition to higher social status may have changed even though the importance of the cultural trait of social status may have been very constant. Social status may thus be an example of a social trait of constant importance, but with a changing genetic predisposition.

Abstract Background Stress fractures are a significant problem among athletes and soldiers and may result in devastating complications or even permanent handicap. Genetic factors may increase the risk, but no major susceptibility genes have been identified. The purpose of this study was to search for possible genetic factors predisposing military conscripts to femoral neck stress fractures. Results Eight genes involved in bone metabolism or pathology ( COL1A1 , COL1A2 , OPG , ESR1, VDR , CTR , LRP5 , IL-6 ) were examined in 72 military conscripts with a femoral neck stress fracture and 120 controls. The risk of femoral neck stress fracture was significantly higher in subjects with low weight and body mass index (BMI). An interaction between the CTR (rs1801197) minor allele C and the VDR C-A haplotype was observed, and subjects lacking the C allele in CTR and/or the C-A haplotype in VDR had a 3-fold higher risk of stress fracture than subjects carrying both (OR = 3.22, 95% CI 1.38-7.49, p = 0.007). In addition, the LRP5 haplotype A-G-G-C alone and in combination with the VDR haplotype C-A was associated with stress fractures through reduced body weight and BMI. Conclusions Our findings suggest that genetic factors play a role in the development of stress fractures in individuals subjected to heavy exercise and mechanical loading. The present results can be applied to the design of future studies that will further elucidate the genetics of stress fractures.

Stress fractures are a significant problem among athletes and soldiers and may result in devastating complications or even permanent handicap. Genetic factors may increase the risk, but no major susceptibility genes have been identified. The purpose of this study was to search for possible genetic factors predisposing military conscripts to femoral neck stress fractures. Eight genes involved in bone metabolism or pathology (COL1A1, COL1A2, OPG, ESR1, VDR, CTR, LRP5, IL-6) were examined in 72 military conscripts with a femoral neck stress fracture and 120 controls. The risk of femoral neck stress fracture was significantly higher in subjects with low weight and body mass index (BMI). An interaction between the CTR (rs1801197) minor allele C and the VDR C-A haplotype was observed, and subjects lacking the C allele in CTR and/or the C-A haplotype in VDR had a 3-fold higher risk of stress fracture than subjects carrying both (OR = 3.22, 95% CI 1.38-7.49, p = 0.007). In addition, the LRP5 haplotype A-G-G-C alone and in combination with the VDR haplotype C-A was associated with stress fractures through reduced body weight and BMI. Our findings suggest that genetic factors play a role in the development of stress fractures in individuals subjected to heavy exercise and mechanical loading. The present results can be applied to the design of future studies that will further elucidate the genetics of stress fractures.

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

<b><i>Background:</i></b> The study aimed to evaluate the association of genetic variants in <i>MIR3142HG</i> with the predisposition of IgA nephropathy (IgAN) in a Chinese Han population. <b><i>Methods:</i></b> Six single-nucleotide polymorphisms (SNPs) in <i>MIR3142HG</i> were chosen for genotyping among 417 IgAN cases and 424 healthy controls using Agena MassARRAY technique. Logistic regression models adjusted for age and gender were used to calculate odds ratios (ORs) and 95% confidence intervals (CI). Haploview and multifactor dimensionality reduction analysis were used to analyze the role of combined SNPs in IgAN risk. <b><i>Results:</i></b> Rs17057846-AA genotype (OR = 2.11, 95% CI: 1.04–4.27, <i>p</i> = 0.039) and rs58747524-CC genotype (OR = 1.89, 95% CI: 1.06–3.38, <i>p</i> = 0.032) had the higher risk for IgAN developing in the overall. Interestingly, rs7727115 had a reduced risk for IgAN in females, while rs17057846, rs2961920, and rs58747524 were related to the increased susceptibility to IgAN in females and the subjects with age ≤35 years; moreover, rs17057846 and rs58747524 conferred to the higher risk for Lee's grade ≥III IgAN (<i>p</i> &#x3c; 0.05 for all). Besides, the combination of rs1582417, rs7727115, and rs2961920 was the best model (testing accuracy = 0.5468, CVC = 10/10, <i>p</i> &#x3c; 0.001) to predict IgAN predisposition compared to the single SNP alone. <b><i>Conclusions:</i></b> Our study firstly indicated that rs17057846 and rs58747524 in <i>MIR3142HG</i> contributed to the elevated risk for IgAN in a Chinese Han population. These results might provide a new insight for the molecular mechanism in the progression of IgAN.

<i>Background:</i> Clinical genetic testing can help identify individuals who are predisposed to a variety of diseases and conditions; thus, it is important to understand attitudes and perceptions of individuals who may consider or who may be offered such testing. <i>Methods:</i> We examined knowledge and attitudes about cancer genetic testing among 59 women of Ashkenazi Jewish descent (age 25–80 years) through six focus group discussions. Participants were asked about their knowledge and experience with hereditary conditions and genetic testing, and attitudes regarding risk management options, genetic privacy, and potential discrimination issues. <i>Results:</i> Although 54% reported having a personal and/or some family history of breast, ovarian, or colorectal cancer, none had undergone cancer genetic counseling or testing and few expressed an interest or intention in doing so. While most endorsed benefits of genetic testing for those with a significant cancer family history, women also expressed concerns over the possible distress of learning that one carried a cancer-predisposing mutation and suggested that increasing cancer screening practices may be preferable to having genetic testing. Participants doubted the ability of state genetic privacy legislation to protect against insurance or employment discrimination. <i>Conclusion:</i> Findings underscore the need for public education on the broad range of benefits and limitations associated with genetic testing, in order to help consumers to appropriately interpret complex information and make decisions about these services.

A system has been developed to identify 11 genetic markers associated with the risk of obesity: rs10852521, rs11075990, rs1121980, rs1421085, rs1477196, rs17817449, rs3751812, rs7206790, rs8047395, rs9940128 (FTO gene) and rs1137101 (LEPR gene) by minisequencing (SNaPshot analysis). The conditions for carrying out the amplification and minisequencing reactions, as well as the compositions of the reaction mixtures, were optimized so that the analysis was carried out for all 11 markers simultaneously. The resulting system was tested and showed a high degree of reproducibility and sensitivity required for the detection of these polymorphisms.

A multiplex system to detect mutations at loci rs5985, rs1799983, rs5918, rs2243093, rs4673, rs4646994, rs1722009, rs3980933, rs71103505 associated with the development of cardiovascular diseases has been developed. These mutations belong to different types - SNP, STR, Ins/Del - therefore, minisequencing and fragment analysis technologies were used to determine them. Oligonucleotide analysis was performed to amplify all loci in a single reaction format. The minisequencing technology, in comparison with fragment analysis, required additional stages of sample preparation; therefore, oligonucleotides for loci with SNP were combined into a separate plex. For the two plexes created, the same composition of the amplification mixture and parameters of the PCR reaction program were optimized, and "bin" panels were developed to interpret the results. The testing of the system confirmed the possibility of detecting mutations at nine loci with high sensitivity and reproducibility.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download ; Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia. ; European Union (EU) Wellcome Trust

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

Abstract

Background
Few studies have explored the association between stair climbing and osteoarthritis (OA) to determine whether the former is a protective or risk factor for the latter. This study prospectively evaluated the associations among stair climbing, genetic susceptibility, and their interaction with the risk of incident hip/knee OA.


Methods
The cohort analyses included 398,939 participants from the UK Biobank. Stair climbing was assessed using a questionnaire. Genetic risk scores (GRSs) consisting of 70, 83, and 87 single-nucleotide polymorphisms for hip, knee, and hip/knee OA were constructed. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations among stair climbing, genetic predisposition, and hip and/or knee OA risk.


Results
After 3,621,735 person-years of follow-up, 31,940 patients developed OA. Stair climbing was positively associated with incident hip/knee (P for trend&lt;0.001) and knee (P for trend&lt;0.0001) OA but not hip OA. After adjustments, compared with no stair climbing, climbing &gt;150 steps/day was associated with a higher risk of hip/knee OA (HR, 1.08; 95% CI, 1.03–1.12) and knee OA (HR, 1.13; 95% CI, 1.06–1.20). Although no significant interaction between stair climbing and the GRS of OA risk was found, the above associations were only significant in participants with middle and high GRSs.


Conclusion
A higher frequency of stair climbing was positively associated with the risk of knee OA but not hip OA, highlighting the importance of avoiding frequent stair climbing in preventing knee OA, especially in genetically predisposed individuals.

Funding Information: Research leading to these results was conducted as part of the InterPregGen study, which received funding from the European Union Seventh Framework Programme under grant agreement no. 282540 and was supported by Wellcome Trust grant 098051. Some data used for the research were obtained from THL Biobank. We thank all study participants for their generous participation at THL Biobank. Part of this work was conducted using the UK Biobank Resource under application number 24711. A full list of acknowledgments appears in Supplementary Note 3. ; Peer reviewed ; Publisher PDF