Elite Athletes: Are the Genes the Champions?

Recent research has analyzed the genetic factors that influence world-class athletic status. Much of what we know comes from association studies, with the ACE I/D and ACTN3 R577X polymorphisms having been extensively studied. The association between the ACTN3 R577X variation and elite athlete status in power sports is strongly documented, yet whether the current body of knowledge on other variants can be extrapolated to athletic champion status remains to be determined. Athletic champion status is a complex polygenic trait in which numerous candidate genes, complex gene–gene interactions, and environment–gene interactions are involved. Besides the need for more studies and new approaches taking into account the complexity of the problem, we believe that factors beyond genetic endowment are likely to have a stronger influence in the attainment of athletic champion status.

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Genetics of alcohol withdrawal

European Psychiatry ◽

10.1016/s0924-9338(00)00220-0 ◽

2000 ◽

Vol 15 (2) ◽

pp. 135-139 ◽

Cited By ~ 31

Author(s):

L.G. Schmidt ◽

T. Sander

Keyword(s):

Candidate Genes ◽

Alcohol Withdrawal ◽

Genetic Factors ◽

Association Studies ◽

Complex Interaction ◽

Multiple Genes

SummaryAlcohol withdrawal is a clinically and etiologically heterogeneous syndrome caused by a complex interaction of environmental (e.g., amount of ethanol) and genetic factors. Multiple genes are considered to be involved in various components of the syndrome, each of them contributing only modestly to withdrawal vulnerability. Association studies using candidate genes of the dopamine, serotonin, gabaergic and opioidergic systems are reviewed and methodological limitations are discussed.

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Genetic Factors Associated With Nodulation and Nitrogen Derived From Atmosphere in a Middle American Common Bean Panel

Frontiers in Plant Science ◽

10.3389/fpls.2020.576078 ◽

2020 ◽

Vol 11 ◽

Author(s):

Atena Oladzad ◽

Abiezer González ◽

Raul Macchiavelli ◽

Consuelo Estevez de Jensen ◽

James Beaver ◽

...

Keyword(s):

Common Bean ◽

Candidate Genes ◽

Genetic Factors ◽

Association Studies ◽

Small Gtpase ◽

Grain Legume ◽

Genome Wide Association Studies ◽

Cellular Polarity ◽

Data Set ◽

Factors Associated

Among grain legume crops, common beans (Phaseolus vulgaris L.) are considered to have poor biological nitrogen (N2) fixation (BNF) capabilities although variation in N2 fixing capabilities exists within the species. The availability of genetic panel varying in BNF capacity and a large-scale single nucleotide polymorphism (SNP) data set for common bean provided an opportunity to discover genetic factors associated with N2 fixation among genotypes in the Middle American gene pool. Using nodulation and percentage of N2-derived from atmosphere (%NDFA) data collected from field trials, at least 11 genotypes with higher levels of BNF capacity were identified. Genome-wide association studies (GWASs) detected both major and minor effects that control these traits. A major nodulation interval at Pv06:28.0–28.27 Mbp was discovered. In this interval, the peak SNP was located within a small GTPase that positively regulates cellular polarity and growth of root hair tips. Located 20 kb upstream of this peak SNP is an auxin-responsive factor AUX/indole acetic auxin (IAA)-related gene involved in auxin transportation during root nodulation. For %NDFA, nitrate (NO3−) transporters, NRT1:2 and NRT1.7 (Pv02:8.64), squamosa promoter binding transcriptome factor (Pv08:28.42), and multi-antimicrobial extrusion protein (MATE) efflux family protein (Pv06:10.91) were identified as candidate genes. Three additional QTLs were identified on chromosomes Pv03:5.24, Pv09:25.89, and Pv11: 32.89 Mbp. These key candidate genes from both traits were integrated with previous results on N2 fixation to describe a BNF pathway.

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A meta-analysis of genome-wide association studies for average daily gain and lean meat percentage in two Duroc pig populations

BMC Genomics ◽

10.1186/s12864-020-07288-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shenping Zhou ◽

Rongrong Ding ◽

Fanming Meng ◽

Xingwang Wang ◽

Zhanwei Zhuang ◽

...

Keyword(s):

Candidate Genes ◽

Growth And Development ◽

Genetic Architecture ◽

Association Studies ◽

Meta Analysis ◽

Average Daily Gain ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Daily Gain

Abstract Background Average daily gain (ADG) and lean meat percentage (LMP) are the main production performance indicators of pigs. Nevertheless, the genetic architecture of ADG and LMP is still elusive. Here, we conducted genome-wide association studies (GWAS) and meta-analysis for ADG and LMP in 3770 American and 2090 Canadian Duroc pigs. Results In the American Duroc pigs, one novel pleiotropic quantitative trait locus (QTL) on Sus scrofa chromosome 1 (SSC1) was identified to be associated with ADG and LMP, which spans 2.53 Mb (from 159.66 to 162.19 Mb). In the Canadian Duroc pigs, two novel QTLs on SSC1 were detected for LMP, which were situated in 3.86 Mb (from 157.99 to 161.85 Mb) and 555 kb (from 37.63 to 38.19 Mb) regions. The meta-analysis identified ten and 20 additional SNPs for ADG and LMP, respectively. Finally, four genes (PHLPP1, STC1, DYRK1B, and PIK3C2A) were detected to be associated with ADG and/or LMP. Further bioinformatics analysis showed that the candidate genes for ADG are mainly involved in bone growth and development, whereas the candidate genes for LMP mainly participated in adipose tissue and muscle tissue growth and development. Conclusions We performed GWAS and meta-analysis for ADG and LMP based on a large sample size consisting of two Duroc pig populations. One pleiotropic QTL that shared a 2.19 Mb haplotype block from 159.66 to 161.85 Mb on SSC1 was found to affect ADG and LMP in the two Duroc pig populations. Furthermore, the combination of single-population and meta-analysis of GWAS improved the efficiency of detecting additional SNPs for the analyzed traits. Our results provide new insights into the genetic architecture of ADG and LMP traits in pigs. Moreover, some significant SNPs associated with ADG and/or LMP in this study may be useful for marker-assisted selection in pig breeding.

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A gene co-association network regulating gut microbial communities in a Duroc pig population

Microbiome ◽

10.1186/s40168-020-00994-8 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Antonio Reverter ◽

Maria Ballester ◽

Pamela A. Alexandre ◽

Emilio Mármol-Sánchez ◽

Antoni Dalmau ◽

...

Keyword(s):

Microbial Communities ◽

Candidate Genes ◽

Relative Abundance ◽

Association Studies ◽

Single Gene ◽

Host Genome ◽

Genome Wide Association Studies ◽

Vaccine Response ◽

Microbiome Composition ◽

Host Genetic

Abstract Background Analyses of gut microbiome composition in livestock species have shown its potential to contribute to the regulation of complex phenotypes. However, little is known about the host genetic control over the gut microbial communities. In pigs, previous studies are based on classical “single-gene-single-trait” approaches and have evaluated the role of host genome controlling gut prokaryote and eukaryote communities separately. Results In order to determine the ability of the host genome to control the diversity and composition of microbial communities in healthy pigs, we undertook genome-wide association studies (GWAS) for 39 microbial phenotypes that included 2 diversity indexes, and the relative abundance of 31 bacterial and six commensal protist genera in 390 pigs genotyped for 70 K SNPs. The GWAS results were processed through a 3-step analytical pipeline comprised of (1) association weight matrix; (2) regulatory impact factor; and (3) partial correlation and information theory. The inferred gene regulatory network comprised 3561 genes (within a 5 kb distance from a relevant SNP–P < 0.05) and 738,913 connections (SNP-to-SNP co-associations). Our findings highlight the complexity and polygenic nature of the pig gut microbial ecosystem. Prominent within the network were 5 regulators, PRDM15, STAT1, ssc-mir-371, SOX9 and RUNX2 which gathered 942, 607, 588, 284 and 273 connections, respectively. PRDM15 modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency and regulates the production of Th1- and Th2-type immune response. The signal transducer STAT1 has long been associated with immune processes and was recently identified as a potential regulator of vaccine response to porcine reproductive and respiratory syndrome. The list of regulators was enriched for immune-related pathways, and the list of predicted targets includes candidate genes previously reported as associated with microbiota profile in pigs, mice and human, such as SLIT3, SLC39A8, NOS1, IL1R2, DAB1, TOX3, SPP1, THSD7B, ELF2, PIANP, A2ML1, and IFNAR1. Moreover, we show the existence of host-genetic variants jointly associated with the relative abundance of butyrate producer bacteria and host performance. Conclusions Taken together, our results identified regulators, candidate genes, and mechanisms linked with microbiome modulation by the host. They further highlight the value of the proposed analytical pipeline to exploit pleiotropy and the crosstalk between bacteria and protists as significant contributors to host-microbiome interactions and identify genetic markers and candidate genes that can be incorporated in breeding program to improve host-performance and microbial traits.

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Genetic Determinants of Paget’s Disease of Bone

Current Osteoporosis Reports ◽

10.1007/s11914-021-00676-w ◽

2021 ◽

Author(s):

Navnit S. Makaram ◽

Stuart H. Ralston

Keyword(s):

Genetic Factors ◽

Association Studies ◽

Paget’S Disease ◽

Paget's Disease ◽

Paget’S Disease Of Bone ◽

Genome Wide Association Studies ◽

Paget's Disease Of Bone ◽

Genome Wide ◽

Family Based

Abstract Purpose of Review To provide an overview of the role of genes and loci that predispose to Paget’s disease of bone and related disorders. Recent Findings Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget’s disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. This brings the total number of genes and loci implicated in PDB to fourteen. Emerging evidence has shown that a number of these genes also predispose to multisystem proteinopathy syndromes where PDB is accompanied by neurodegeneration and myopathy due to the accumulation of abnormal protein aggregates, emphasising the importance of defects in autophagy in the pathogenesis of PDB. Summary Genetic factors play a key role in the pathogenesis of PDB and the studies in this area have identified several genes previously not suspected to play a role in bone metabolism. Genetic testing coupled to targeted therapeutic intervention is being explored as a way of halting disease progression and improving outcome before irreversible skeletal damage has occurred.

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Association study of performance-related polymorphisms in Brazilian combat-sport athletes highlights variants in the GABPβ1 gene

Physiological Genomics ◽

10.1152/physiolgenomics.00118.2020 ◽

2020 ◽

Author(s):

João Paulo L. F. Guilherme ◽

Tacito P Souza-Junior ◽

Antônio H Lancha Júnior

Keyword(s):

Association Study ◽

Nucleotide Polymorphisms ◽

Combat Sport ◽

Single Nucleotide ◽

Athletic Status ◽

Sport Athlete ◽

World Class ◽

Control Association ◽

Brazilian Cohort ◽

Aerobic Energy Production

Combat sports have an intermittent nature, with mixed anaerobic and aerobic energy production. Here, we investigated whether polymorphisms that have been previously suggested as genetic markers for endurance or power phenotypes were associated with combat-sport athletic status. A total of 23 previously reported performance-related polymorphisms were examined in a Brazilian cohort of 1,129 individuals (164 combat-sport athletes and 965 controls), using a case-control association study. We found that the GABPβ1 gene (also known as NRF2) was associated with athletic status, with the minor G (rs7181866) and T (rs8031031) alleles overrepresented in athletes (P ≤ 0.003), especially among world-class competitors (P ≤ 0.0002). These findings indicate that single nucleotide polymorphisms (SNPs) within the GABPβ1 gene increase the likelihood of an individual being a combat-sport athlete, possibly due to a better mitochondrial response to intermittent exercises.

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The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

Biologia ◽

10.2478/s11756-008-0020-4 ◽

2008 ◽

Vol 63 (1) ◽

Author(s):

Eva Slabá ◽

Pavol Joppa ◽

Ján Šalagovič ◽

Ružena Tkáčová

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Inflammatory Response ◽

Candidate Genes ◽

Pulmonary Disease ◽

Gene Polymorphisms ◽

Association Studies ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Positional Candidate ◽

Linkage Analyses

AbstractChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Irreversible airflow limitation, both progressive and associated with an inflammatory response of the lungs to noxious particles or gases, is a hallmark of the disease. Cigarette smoking is the most important environmental risk factor for COPD, nevertheless, only approximately 20–30% of smokers develop symptomatic disease. Epidemiological studies, case-control studies in relatives of patients with COPD, and twin studies suggest that COPD is a genetically complex disease with environmental factors and many involved genes interacting together. Two major strategies have been employed to identify the genes and the polymorphisms that likely contribute to the development of complex diseases: association studies and linkage analyses. Biologically plausible pathogenetic mechanisms are prerequisites to focus the search for genes of known function in association studies. Protease-antiprotease imbalance, generation of oxidative stress, and chronic inflammation are recognized as the principal mechanisms leading to irreversible airflow obstruction and parenchymal destruction in the lung. Therefore, genes which have been implicated in the pathogenesis of COPD are involved in antiproteolysis, antioxidant barrier and metabolism of xenobiotic substances, inflammatory response to cigarette smoke, airway hyperresponsiveness, and pulmonary vascular remodelling. Significant associations with COPD-related phenotypes have been reported for polymorphisms in genes coding for matrix metalloproteinases, microsomal epoxide hydrolase, glutathione-S-transferases, heme oxygenase, tumor necrosis factor, interleukines 1, 8, and 13, vitamin D-binding protein and β-2-adrenergic receptor (ADRB2), whereas adequately powered replication studies failed to confirm most of the previously observed associations. Genome-wide linkage analyses provide us with a novel tool to identify the general locations of COPD susceptibility genes, and should be followed by association analyses of positional candidate genes from COPD pathophysiology, positional candidate genes selected from gene expression studies, or dense single nucleotide polymorphism panels across regions of linkage. Haplotype analyses of genes with multiple polymorphic sites in linkage disequilibrium, such as the ADRB2 gene, provide another promising field that has yet to be explored in patients with COPD. In the present article we review the current knowledge about gene polymorphisms that have been recently linked to the risk of developing COPD and/or may account for variations in the disease course.

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A description of large-scale metabolomics studies: increasing value by combining metabolomics with genome-wide SNP genotyping and transcriptional profiling

Journal of Endocrinology ◽

10.1530/joe-12-0144 ◽

2012 ◽

Vol 215 (1) ◽

pp. 17-28 ◽

Cited By ~ 18

Author(s):

Georg Homuth ◽

Alexander Teumer ◽

Uwe Völker ◽

Matthias Nauck

Keyword(s):

Blood Cells ◽

Large Scale ◽

Genetic Factors ◽

Association Studies ◽

Transcriptional Profiling ◽

Genome Wide Association Studies ◽

Protein Levels ◽

Future Developments ◽

Genome Wide ◽

Metabolome Data

The metabolome, defined as the reflection of metabolic dynamics derived from parameters measured primarily in easily accessible body fluids such as serum, plasma, and urine, can be considered as the omics data pool that is closest to the phenotype because it integrates genetic influences as well as nongenetic factors. Metabolic traits can be related to genetic polymorphisms in genome-wide association studies, enabling the identification of underlying genetic factors, as well as to specific phenotypes, resulting in the identification of metabolome signatures primarily caused by nongenetic factors. Similarly, correlation of metabolome data with transcriptional or/and proteome profiles of blood cells also produces valuable data, by revealing associations between metabolic changes and mRNA and protein levels. In the last years, the progress in correlating genetic variation and metabolome profiles was most impressive. This review will therefore try to summarize the most important of these studies and give an outlook on future developments.

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The genetic epidemiology of personality disorders

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2010.12.1/trkjennerud ◽

2010 ◽

Vol 12 (1) ◽

pp. 103-114 ◽

Cited By ~ 2

Keyword(s):

Personality Disorders ◽

Genetic Factors ◽

Association Studies ◽

Molecular Genetic ◽

Cluster Structure ◽

Epidemiologic Studies ◽

Axis Ii ◽

Candidate Gene Association ◽

Axis I ◽

Dsm Iv

Genetic epidemiologic studies indicate that all ten personality disorders (PDs) classified on the DSM-IV axis II are modestly to moderately heritable. Shared environmental and nonadditive genetic factors are of minor or no importance. No sex differences have been identified, Multivariate studies suggest that the extensive comorbidity between the PDs can be explained by three common genetic and environmental risk factors. The genetic factors do not reflect the DSM-IV cluster structure, but rather: i) broad vulnerability to PD pathology or negative emotionality; ii) high impulsivity/low agreeableness; and iii) introversion. Common genetic and environmental liability factors contribute to comorbidity between pairs or clusters of axis I and axis II disorders. Molecular genetic studies of PDs, mostly candidate gene association studies, indicate that genes linked to neurotransmitter pathways, especially in the serotonergic and dopaminergic systems, are involved. Future studies, using newer methods like genome-wide association, might take advantage of the use of endophenotypes.

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Identification of Novel Genome-Wide Associations for Oral Inflammatory Traits

10.21203/rs.3.rs-104530/v1 ◽

2020 ◽

Author(s):

Yanjiao Jin ◽

Jie Yang ◽

Shuyue Zhang ◽

Jin Li ◽

Songlin Wang

Keyword(s):

Candidate Genes ◽

Immune Regulation ◽

Functional Annotation ◽

Inflammatory Diseases ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Protein Protein Interaction ◽

Genome Wide ◽

Causal Variants

Abstract Background: Oral diseases impact the majority of the world’s population. The following traits are common in oral inflammatory diseases: mouth ulcers, painful gums, bleeding gums, loose teeth, and toothache. Despite the prevalence of genome-wide association studies, the associations between these traits and common genomic variants, and whether pleiotropic loci are shared by some of these traits remain poorly understood. Methods: In this work, we conducted multi-trait joint analyses based on the summary statistics of genome-wide association studies of these five oral inflammatory traits from the UK Biobank, each of which is comprised of over 10,000 cases and over 300,000 controls. We estimated the genetic correlations between the five traits. We conducted fine-mapping and functional annotation based on multi-omics data to better understand the biological functions of the potential causal variants at each locus. To identify the pathways in which the candidate genes were mainly involved, we applied gene-set enrichment analysis, and further performed protein-protein interaction (PPI) analyses.Results: We identified 39 association signals that surpassed genome-wide significance, including three that were shared between two or more oral inflammatory traits, consistent with a strong correlation. Among these genome-wide significant loci, two were novel for both painful gums and toothache. We performed fine-mapping and identified causal variants at each novel locus. Further functional annotation based on multi-omics data suggested IL10 and IL12A/TRIM59 as potential candidate genes at the novel pleiotropic loci, respectively. Subsequent analyses of pathway enrichment and protein-protein interaction networks suggested the involvement of candidate genes at genome-wide significant loci in immune regulation.Conclusions: Our results highlighted the importance of immune regulation in the pathogenesis of oral inflammatory diseases. Some common immune-related pleiotropic loci or genetic variants are shared by multiple oral inflammatory traits. These findings will be beneficial for risk prediction, prevention, and therapy of oral inflammatory diseases.

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