scholarly journals Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position

2016 ◽  
Vol 48 (3) ◽  
pp. 196-201 ◽  
Author(s):  
S. M. Heffernan ◽  
L. P. Kilduff ◽  
R. M. Erskine ◽  
S. H. Day ◽  
J. S. McPhee ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Odds Ratio ◽  
Genomic Dna ◽  
Multiple Comparisons ◽  
Rugby Union ◽  
Genetic Studies ◽  
P Values ◽  
Taqman Probes ◽  
Genotype Frequencies ◽  
Caucasian Men

We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league) and compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers, and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using χ2 and odds ratio (OR) statistics. Correction of P values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared with forwards (24.8%, P = 0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ2 = 6.672, P = 0.04; OR = 1.60) and forwards (47.5%; χ2 = 11.768, P = 0.01; OR = 2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards, while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intrasport positional differences exist, instead of combining several sports with varied demands and athlete characteristics.

scholarly journals Padded Headgear does not Reduce the Incidence of Match Concussions in Professional Men’s Rugby Union: A Case-control Study of 417 Cases

2021 ◽  
Author(s):  
Keith A. Stokes ◽  
Matthew Cross ◽  
Sean Williams ◽  
Carly McKay ◽  
Brent E. Hagel ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Head Injuries ◽  
Median Number ◽  
Case Control ◽  
Rugby Union ◽  
Return To Play ◽  
Injury Incidence ◽  
Video Footage ◽  
Four Seasons ◽  
Nested Case Control

AbstractConcussion is the most common match injury in rugby union. Some players wear padded headgear, but whether this protects against concussion is unclear. In professional male rugby union players, we examined: (i) the association between the use of headgear and match concussion injury incidence, and (ii) whether wearing headgear influenced time to return to play following concussion. Using a nested case-control within a cohort study, four seasons (2013–2017) of injury data from 1117 players at the highest level of rugby union in England were included. Cases were physician-diagnosed concussion injuries. Controls were other contact injuries (excluding all head injuries). We determined headgear use by viewing video footage. Sixteen percent of cases and controls wore headgear. Headgear use had no significant effect on concussion injury incidence (adjusted odds ratio=1.05, 95% CI: 0.71–1.56). Median number of days absent for concussion whilst wearing headgear was 8 days, compared with 7 days without headgear. Having sustained a concussion in the current or previous season increased the odds of concussion more than four-fold (odds ratio=4.55, 95% CI: 3.77–5.49). Wearing headgear was not associated with lower odds of concussions or a reduced number of days' absence following a concussion.

Has the time come to integrate genetic risk scores into clinical practice?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F.V Moniz Mendonca ◽  
M.I Mendonca ◽  
A Pereira ◽  
J Monteiro ◽  
J Sousa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Practice ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Risk Scores ◽  
Cumulative Number ◽  
Genetic Risk Scores ◽  
Risk Alleles ◽  
Cad Risk

Abstract Background The risk for Coronary Artery Disease (CAD) is determined by both genetic and environmental factors, as well as by the interaction between them. It is estimated that genetic factors could account for 40% to 55% of the existing variability among the population (inheritability). Therefore, some authors have advised that it is time we integrated genetic risk scores into clinical practice. Aim The aim of this study was to evaluate the magnitude of the association between an additive genetic risk score (aGRS) and CAD based on the cumulative number of risk alleles in these variants, and to estimate whether their use is valuable in clinical practice. Methods A case-control study was performed in a Portuguese population. We enrolled 3120 participants, of whom 1687 were CAD patients and 1433 were normal controls. Controls were paired to cases with respect to gender and age. 33 genetic variants known to be associated with CAD were selected, and an aGRS was calculated for each individual. The aGRS was further subdivided into deciles groups, in order to estimate the CAD risk in each decile, defined by the number of risk alleles. The magnitude of the risk (odds ratio) was calculated for each group by multiple logistic regression using the 5th decile as the reference group (median). In order to evaluate the ability of the aGRS to discriminate susceptibility to CAD, two genetic models were performed, the first with traditional risk factors (TRF) and second with TRF plus aGRS. The AUC of the two ROC curves was calculated. Results A higher prevalence of cases over controls became apparent from the 6th decile of the aGRS, reflecting the higher number of risk alleles present (see figure). The difference in CAD risk was only significant from the 6th decile, increasing gradually until the 10th decile. The odds ratio (OR) for the last decile related to 5th decile (median) was 1.87 (95% CI:1.36–2.56; p<0.0001). The first model yielded an AUC=0.738 (95% CI:0.720–0.755) and the second model was slightly more discriminative for CAD risk (AUC=0.748; 95% CI:0.730–0.765). The DeLong test was significant (p=0.0002). Conclusion Adding an aGRS to the non-genetic risk factors resulted in a modest improvement in the ability to discriminate the risk of CAD. Such improvement, even if statistically significant, does not appear to be of real value in clinical practice yet. We anticipate that with the development of further knowledge about different SNPs and their complex interactions, and with the inclusion of rare genetic variants, genetic risk scores will be better suited for use in a clinical setting. Funding Acknowledgement Type of funding source: None

PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men

2005 ◽  
Vol 99 (1) ◽  
pp. 344-348 ◽  
Author(s):  
Alejandro Lucia ◽  
Félix Gómez-Gallego ◽  
Inês Barroso ◽  
Manuel Rabadán ◽  
Fernando Bandrés ◽  
...  
Keyword(s):  
Early Death ◽  
Endurance Capacity ◽  
Targeted Prevention ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Genotype Frequencies ◽  
Caucasian Men ◽  
World Class ◽  
Genetic Stratification

Animal and human data indicate a role for the peroxisome proliferator-activated receptor-γ coactivator 1α ( PPARGC1A) gene product in the development of maximal oxygen uptake (V̇o2 max), a determinant of endurance capacity, diabetes, and early death. We tested the hypothesis that the frequency of the minor Ser482 allele at the PPARGC1A locus is lower in World-class Spanish male endurance athletes (cases) [ n = 104; mean (SD) age: 26.8 (3.8) yr] than in unfit United Kingdom (UK) Caucasian male controls [ n = 100; mean (SD) age: 49.3 (8.1) yr]. In cases and controls, the Gly482Ser genotype met Hardy-Weinberg expectations ( P > 0.05 in both groups tested separately). Cases had significantly higher V̇o2 max [73.4 (5.7) vs. 29.4 ml·kg−1·min−1 (3.8); P < 0.0001] and were leaner [body mass index: 20.6 (1.5) vs. 27.6 kg/m2 (3.9); P < 0.0001] than controls. In unadjusted χ2 analyses, the frequency of the minor Ser482 allele was significantly lower in cases than in controls (29.1 vs. 40.0%; P = 0.01). To assess the possibility that genetic stratification could confound these observations, we also compared Gly482Ser genotype frequencies in Spanish ( n = 164) and UK Caucasian men ( n = 381) who were unselected for their level of fitness. In these analyses, Ser482 allele frequencies were very similar (36.9% in Spanish vs. 37.5% in UK Caucasians, P = 0.83), suggesting that confounding by genetic stratification is unlikely to explain the association between Gly482Ser genotype and endurance capacity. In summary, our data indicate a role for the Gly482Ser genotype in determining aerobic fitness. This finding has relevance from the perspective of physical performance, but it may also be informative for the targeted prevention of diseases associated with low fitness such as Type 2 diabetes.

scholarly journals Coffee Consumption and Cardiovascular Diseases: A Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2218
Author(s):  
Shuai Yuan ◽  
Paul Carter ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Intracerebral Hemorrhage ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Uk Biobank ◽  
The Uk

Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.

scholarly journals Biostatistical Analysis: A Primer for Clinical Exercise Physiology, Part 1

2018 ◽  
Vol 7 (3) ◽  
pp. 63-69
Author(s):  
Suzanne L. Havstad ◽  
George W. Divine
Keyword(s):  
Sample Size ◽  
Gold Standard ◽  
Exercise Physiology ◽  
Analytical Techniques ◽  
Multiple Comparisons ◽  
Inference Process ◽  
P Values ◽  
Advantages And Disadvantages ◽  
Point Estimates ◽  
Biostatistical Analysis

ABSTRACT In this first of a two-part series on introductory biostatistics, we briefly describe common designs. The advantages and disadvantages of six design types are highlighted. The randomized clinical trial is the gold standard to which other designs are compared. We present the benefits of randomization and discuss the importance of power and sample size. Sample size and power calculations for any design need to be based on meaningful effects of interest. We give examples of how the effect of interest and the sample size interrelate. We also define concepts helpful to the statistical inference process. When drawing conclusions from a completed study, P values, point estimates, and confidence intervals will all assist the researcher. Finally, the issue of multiple comparisons is briefly explored. The second paper in this series will describe basic analytical techniques and discuss some common mistakes in the interpretation of data.

High-impact rare genetic variants in severe schizophrenia

2021 ◽  
Vol 118 (51) ◽  
pp. e2112560118
Author(s):  
Anthony W. Zoghbi ◽  
Ryan S. Dhindsa ◽  
Terry E. Goldberg ◽  
Aydan Mehralizade ◽  
Joshua E. Motelow ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Odds Ratio ◽  
High Impact ◽  
Psychiatric Genetics ◽  
Loss Of Function ◽  
Treatment Resistant ◽  
Complex Disorders ◽  
Extreme Phenotype ◽  
Case Selection ◽  
Rare Genetic Variants

Extreme phenotype sequencing has led to the identification of high-impact rare genetic variants for many complex disorders but has not been applied to studies of severe schizophrenia. We sequenced 112 individuals with severe, extremely treatment-resistant schizophrenia, 218 individuals with typical schizophrenia, and 4,929 controls. We compared the burden of rare, damaging missense and loss-of-function variants between severe, extremely treatment-resistant schizophrenia, typical schizophrenia, and controls across mutation intolerant genes. Individuals with severe, extremely treatment-resistant schizophrenia had a high burden of rare loss-of-function (odds ratio, 1.91; 95% CI, 1.39 to 2.63; P = 7.8 × 10−5) and damaging missense variants in intolerant genes (odds ratio, 2.90; 95% CI, 2.02 to 4.15; P = 3.2 × 10−9). A total of 48.2% of individuals with severe, extremely treatment-resistant schizophrenia carried at least one rare, damaging missense or loss-of-function variant in intolerant genes compared to 29.8% of typical schizophrenia individuals (odds ratio, 2.18; 95% CI, 1.33 to 3.60; P = 1.6 × 10−3) and 25.4% of controls (odds ratio, 2.74; 95% CI, 1.85 to 4.06; P = 2.9 × 10−7). Restricting to genes previously associated with schizophrenia risk strengthened the enrichment with 8.9% of individuals with severe, extremely treatment-resistant schizophrenia carrying a damaging missense or loss-of-function variant compared to 2.3% of typical schizophrenia (odds ratio, 5.48; 95% CI, 1.52 to 19.74; P = 0.02) and 1.6% of controls (odds ratio, 5.82; 95% CI, 3.00 to 11.28; P = 2.6 × 10−8). These results demonstrate the power of extreme phenotype case selection in psychiatric genetics and an approach to augment schizophrenia gene discovery efforts.

Meta-analysis of genetic association studies on gestational diabetes mellitus

2021 ◽  
Author(s):  
Ravi BHUSHAN ◽  
Sonal Upadhyay ◽  
Shally AWASTHI ◽  
Monika Panday
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Secretion ◽  
Gestational Diabetes ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Genetic Models ◽  
Increased Risk ◽  
Tcf7l2 Rs7903146 ◽  
Gckr Rs780094

Abstract Background Several molecular epidemiological studies have analyzed the associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, all these studies suffer from inconsistent and conflicting results owing to relatively smaller sample sizes, fewer genetic variants included in the research, and limited statistical power. Hence, a coherent review and meta-analysis were carried out to provide a quantitative summary related to the associations of commonly studied SNPs with GDM risk. Methods Eligible studies were retrieved from PubMed,updated on Dec. 2019. Based on several inclusion and exclusion criteria, 71 articles with 42928 GDM patients and 77793 controls were finally considered for meta-analysis. The genotype data from 23 variants of sixteen genes were statistically analyzed using RevMan v 5.2 software. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the research article. Heterogeneity among studies was tested by I2 and odds ratio with 95% confidence interval (CI) was carried out for all five genetic models. Results The overall combined odds ratio reveals that variants like MTNR1B (rs1083963, rs1387153), GCK (rs1799884), CANP10 (rs3792267), and GCKR (rs780094) are significantly associated with GDM in all genetic models while CANP10 (rs5030952), ADRB (rs4994) and FTO (rs8050136) are not significantly associated with GDM in any genetic models. Variants MTNR1B (rs1083963, rs1387153) and GCK (rs1799884) are associated with increased risk (OR>1, p<0.05) of GDM, and all these are related to insulin secretion. Other variants related to insulin secretion like TCF7L2 (rs7903146) and SLC30A8 (rs1326634) are also associated with increased risk (OR>1, p<0.05) of GDM. On the contrary, CANP10 (rs3792267) and GCKR (rs780094) are found associated with decreased risk (OR<1, p<0.05) of GDM. Other variants are significantly associated with the GDM in at least one or more genetic models. Conclusion Our study identified that most of the variants related to insulin secretions like MTNR1B (rs1083963), GCK (rs1799884), TCF7L2 (rs7903146), GCKR (rs780094), and SLC30A8 (rs1326634) are more strongly associated (p<0.005) with GDM as compared to the variants related to the insulin resistance like PPARG (rs1801282), IRS1 (rs1801278) and ADIPOQ (rs266729).

"MULTIPLE-COMPARISONS" PROBLEM

PEDIATRICS ◽  
1989 ◽  
Vol 84 (6) ◽  
pp. A30-A30
Author(s):  
Student
Keyword(s):  
Null Hypothesis ◽  
Multiple Comparisons ◽  
P Value ◽  
Expected Number ◽  
P Values ◽  
A Value ◽  
True Null Hypotheses ◽  
The Individual

Often investigators report many P values in the same study. The expected number of P values smaller than 0.05 is 1 in 20 tests of true null hypotheses; therefore the probability that at least one P value will be smaller than 0.05 increases with the number of tests, even when the null hypothesis is correct for each test. This increase is known as the "multiple-comparisons" problem...One reasonable way to correct for multiplicity is simply to multiply the P value by the number of tests. Thus, with five tests, an orignal 0.05 level for each is increased, perhaps to a value as high as 0.25 for the set. To achieve a level of not more than 0.05 for the set, we need to choose a level of 0.05/5 = 0.01 for the individual tests. This adjustment is conservative. We know only that the probability does not exceed 0.05 for the set.

scholarly journals Different Methylation of CpG-SNPs in Behcet’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Yang Huang ◽  
Handan Tan ◽  
Qingfeng Cao ◽  
Gangxiang Yuan ◽  
Guannan Su ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Genetic Variants ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Association Studies ◽  
Statistical Significance ◽  
Multiple Comparisons ◽  
Healthy Individuals ◽  
Behcet's Disease ◽  
Second Stage

Purpose. We recently performed an Epigenome-Wide Association Studies (EWAS) study in Behcet’s disease (BD) and identified various cytosine–phosphate–guanine (CpG) loci that were aberrantly methylated. In the current study, we wanted to investigate whether these sites contained genetic polymorphisms and whether the frequency of these polymorphisms was altered in BD.Methods. A two-stage study was performed. The first stage involved 358 BD patients and 704 healthy controls to investigate genetic variants of 10 CpG-SNPs (rs10454134, rs176249, rs3808620, rs10176517, rs11247118, rs78016579, rs9461624, rs10492166, rs34929465, and rs6507921) using an iPLEX Gold genotyping assay and a Sequenom MassARRAY. In the second stage, an additional 172 independent BD patients and 330 healthy individuals are to confirm trends found in the first stage.Results. A higher frequency of both the rs10454134 AG genotypes (p = 0.008, OR = 1.413, 95% CI = 1.094-1.826) and a lower GG genotype frequency (p = 0.003, OR = 0.630, 95% CI = 0.465-0.854) were found in BD patients compared to the controls in the first stage. However, after correcting for multiple comparisons, all associations identified in the first stage lost statistical significance. The frequencies of the other CpG-SNPs investigated were not different between BD patients and controls. The second stage was designed using an additional cohort to confirm the association with CpG-SNP, rs10454134. The data failed to confirm the association between this CpG-SNP and BD.Conclusions. This study did not show an association between BD and CpG-SNPs in gene sites that were earlier shown to be aberrantly methylated.

scholarly journals Association between Platelet-Specific Collagen Receptor Glycoprotein 6 Gene Variants, Selected Biomarkers, and Recurrent Pregnancy Loss in Korean Women

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 862
Author(s):  
Hui Jeong An ◽  
Eun Hee Ahn ◽  
Jung Oh Kim ◽  
Chang Soo Ryu ◽  
Han Sung Park ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Pregnancy Loss ◽  
Adjusted Odds Ratio ◽  
Recurrent Pregnancy Loss ◽  
Korean Women ◽  
Chain Reaction ◽  
Genotype Frequencies ◽  
Polymerase Chain

This paper investigates whether glycoprotein 6 (GP6) gene polymorphisms are a risk factor for recurrent pregnancy loss (RPL) in Korean women. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and real-time polymerase chain reaction amplification. We identified five polymorphisms in the GP6 gene: rs1654410 T>C, rs1671153 T>G, rs1654419 G>A, rs12610286 A>G, and rs1654431 G>A. GP6 rs1654410 CC was associated with decreased RPL risk (adjusted odds ratio = 0.292, 95% confidence interval = 0.105–0.815, p = 0.019), and recessive genotypes were also significantly associated with decreased RPL risk (adjusted odds ratio = 0.348, 95% confidence interval = 0.128−0.944, p = 0.038). GP6 rs1654419 GA was associated with decreased RPL risk (adjusted odds ratio = 0.607, 95% confidence interval = 0.375-0.982, p = 0.042), and dominant genotypes were significantly associated with decreased RPL risk (adjusted odds ratio = 0.563, 95% confidence interval = 0.358−0.885, p = 0.013). Altogether, the genotype frequencies of GP6 rs1654410 T>C and GP6 rs1654419 G>A were significantly different between RPL patients and control participants. Therefore, although GP6 polymorphisms may be useful as biomarkers of RPL, additional studies with heterogeneous cohorts are required to better understand the influence of GP6 and assess its performance as a biomarker.

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