Association studies reveal the effect of genetic variation in lncRNA UGTRL and its putative target PtoUGT88A1 on wood formation in Populus tomentosa

MicroRNAs (miRNAs), important posttranscriptional regulators of gene expression, play a crucial role in plant growth and development. A single miRNA can regulate numerous target genes, making the determination of its function and interaction with targets challenging. We identified PtomiR403b target to PtoGT31B-1, which encodes a galactosyltransferase responsible for the biosynthesis of cell wall polysaccharides. We performed an association study and epistasis and Mendelian randomization (MR) analyses to explore how the genetic interaction between PtoMIR403b and its target PtoGT31B-1 underlies wood formation. Single nucleotide polymorphism (SNP)-based association studies identified 25 significant associations (P < 0.01, Q < 0.05), and PtoMIR403b and PtoGT31B-1 were associated with five traits, suggesting a role for PtomiR403b and PtoGT31B-1 in wood formation. Epistasis analysis identified 93 significant pairwise epistatic associations with 10 wood formation traits, and 37.89% of the SNP-SNP pairs indicated interactions between PtoMIR403b and PtoGT31B-1. We performed an MR analysis to demonstrate the causality of the relationships between SNPs in PtoMIR403b and wood property traits and that PtoMIR403b modulates wood formation by regulating expression of PtoGT31B-1. Therefore, our findings will facilitate dissection of the functions and interactions with miRNA-targets.

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A model-based approach to capture genetic variation for future association studies

Genome Research ◽

10.1101/gr.5675406 ◽

2006 ◽

Vol 17 (1) ◽

pp. 88-95 ◽

Cited By ~ 8

Author(s):

S. Eyheramendy ◽

J. Marchini ◽

G. McVean ◽

S. Myers ◽

P. Donnelly

Keyword(s):

Genetic Variation ◽

Association Studies ◽

Model Based

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Genetic variation in the first intron and exon of the myostatin gene in several Indonesian cattle populations

Veterinary World ◽

10.14202/vetworld.2021.1197-1201 ◽

2021 ◽

pp. 1197-1201

Author(s):

Peni Wahyu Prihandini ◽

Almira Primasari ◽

Aryogi Aryogi ◽

Jauhari Efendy ◽

Muchamad Luthfi ◽

...

Keyword(s):

Genetic Variation ◽

Transforming Growth Factor ◽

Association Studies ◽

Negative Regulator ◽

Reaction Products ◽

Myostatin Gene ◽

Mstn Gene ◽

Synonymous Mutations ◽

Intron 1 ◽

Exon 1

Background and Aim: Myostatin (MSTN), a member of the transforming growth factor-β family, is a negative regulator of muscle mass. This study aimed to detect the genetic variation of the 1160 bp fragment of exon 1 and part of intron 1 of the MSTN gene in several cattle populations raised in Indonesia. Materials and Methods: Polymerase chain reaction products of the MSTN gene amplified from 92 animals representing 10 cattle populations (Peranakan Ongole [PO], Belgian Blue x PO cross, Rambon, PO x Bali cross, Jabres, Galekan, Sragen, Donggala, Madura, and Bali) were sequenced, compared, and aligned with bovine MSTN of Bos taurus (GenBank Acc. No. AF320998.1) and Bos indicus (GenBank Acc. No. AY794986.1). Results: Four nucleotide substitutions (nt 1045 and 1066 in intron 1; nt 262 and 418 in exon 1) and two indels (nt 807 and 869 in intron 1) were synonymous mutations. Among these substitutions, only the nt 262G>C and nt 418A>G loci were polymorphic in all populations, except Bali cattle. The frequencies of the nt 262C (0.82) and nt 418A (0.65) alleles were highest. For the nt 262G>C locus, the CC genotype had the highest frequency (0.66) followed by GC (0.30) and CC (0.03). For the nt 418A>G locus, the AG genotype had the highest frequency (0.52) followed by AA (0.39) and GG (0.09). Conclusion: The results, showing genetic variations in exon 1 and intron 1 of the MSTN gene, might be helpful for future association studies.

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Genome-Wide Association Studies Reveal Genetic Variation and Candidate Genes of Drought Stress Related Traits in Cotton (Gossypium hirsutum L.)

Frontiers in Plant Science ◽

10.3389/fpls.2018.01276 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 18

Author(s):

Sen Hou ◽

Guozhong Zhu ◽

Yuan Li ◽

Weixi Li ◽

Jie Fu ◽

...

Keyword(s):

Genetic Variation ◽

Drought Stress ◽

Gossypium Hirsutum ◽

Candidate Genes ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Gossypium Hirsutum L ◽

Genome Wide

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Abstract 18134: Phenome-wide Study of Electronic Medical Record Data Reveals Novel Association of Natriuretic Peptide A Genetic Variant With Rheumatoid Arthritis

Circulation ◽

10.1161/circ.132.suppl_3.18134 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Naveen Pereira ◽

Gregory Jenkins ◽

Ifthikar Kullo ◽

Suzette Bielinski ◽

John Burnett ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Genetic Variation ◽

Medical Record ◽

Electronic Medical Record ◽

Natriuretic Peptide ◽

Genetic Variants ◽

Association Studies ◽

Disease Phenotypes ◽

Novel Association ◽

The Relationship

Introduction: Phenome-wide association studies (PheWAS) using electronic medical record (EMR)-linked biobanks have been used not only to identify and replicate known associations of genetic variants with disease phenotypes but have also resulted in the discovery of potentially novel genotype-phenotype relationships. The natriuretic peptide (NP) system plays an important role in a broad range of disease processes including cardiovascular and inflammatory diseases. We hypothesized that performing a PheWAS using previously known functional genetic variants of the NP system may result in novel disease associations that could provide mechanistic insights in an unbiased manner. Methods: We scanned for associations between 9 single-nucleotide polymorphisms (SNPs) in the NP system and 27 EMR-derived chronic disease phenotypes in 3,025 individuals participating in a case-control study of peripheral arterial disease. The EMR phenotypes were identified using two or more ICD-9-CM diagnosis codes based on the AHRQ Clinical Classifications Software (CCS). The relationship of SNPs and phenotypes were modeled using logistic regression adjusting for gender. Results: We identified rs5065, a SNP located in the stop codon of exon 3 of the NPPA gene, to be the strongest associated SNP with rheumatoid arthritis (RA) (OR=0.78, p=0.0008, q-value=0.11). The SNP leads to the extension of atrial natriuretic peptide (ANP) by 2 additional arginines at the C terminus. Cardiovascular disease is known to be the leading cause of death in patients with RA and ANP plays an important immunomodulatory role by inhibiting inducible nitric oxide synthase, reducing TNF-α production and attenuating prostaglandin E2 production in macrophages. Circulating NPs have been used to screen for occult cardiac disease and are associated with mortality in RA. This study demonstrates for the first time the importance of the relationship between genetic variation in the NP system and RA. Conclusions: PheWAS was successfully used as a tool to identify a novel association of functional genetic variation in the NPPA gene with RA. The observation is hypothesis generating and further replication studies are required to determine the role of rs5065 in cardiovascular outcomes of RA.

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The Y Chromosome: A Complex Locus for Genetic Analyses of Complex Human Traits

Genes ◽

10.3390/genes11111273 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1273

Author(s):

Katherine Parker ◽

A. Mesut Erzurumluoglu ◽

Santiago Rodriguez

Keyword(s):

Population Genetics ◽

Genetic Variation ◽

Y Chromosome ◽

Complex Traits ◽

Association Studies ◽

Epidemiological Studies ◽

Complex Locus ◽

Complex Human Traits ◽

Human Complex ◽

Human Y Chromosome

The Human Y chromosome (ChrY) has been demonstrated to be a powerful tool for phylogenetics, population genetics, genetic genealogy and forensics. However, the importance of ChrY genetic variation in relation to human complex traits is less clear. In this review, we summarise existing evidence about the inherent complexities of ChrY variation and their use in association studies of human complex traits. We present and discuss the specific particularities of ChrY genetic variation, including Y chromosomal haplogroups, that need to be considered in the design and interpretation of genetic epidemiological studies involving ChrY.

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Transcriptome analysis and association mapping reveal the genetic regulatory network response to cadmium stress in Populus tomentosa

Journal of Experimental Botany ◽

10.1093/jxb/eraa434 ◽

2020 ◽

Author(s):

Mingyang Quan ◽

Xin Liu ◽

Liang Xiao ◽

Panfei Chen ◽

Fangyuan Song ◽

...

Keyword(s):

Stress Responses ◽

Target Genes ◽

Leaf Growth ◽

Association Studies ◽

Cadmium Stress ◽

Populus Tomentosa ◽

Genetic Networks ◽

Hormone Regulation ◽

Lncrna Gene ◽

Cd Tolerance

Abstract Long non-coding RNAs (lncRNAs) play essential roles in plant abiotic stress responses, but the response of lncRNA-mediated genetic networks to cadmium (Cd) treatment remain elusive in trees, the promising candidates for phytoremediation of Cd contamination. We identified 172 Cd-responsive lncRNAs and 295 differentially expressed target genes in the leaves of Cd-treated Populus tomentosa. Functional annotation revealed that these lncRNAs were involved in various processes, including photosynthesis, hormone regulation, and phenylalanine metabolism. Association studies identified 78 significant associations, representing 14 Cd-responsive lncRNAs and 28 target genes for photosynthetic and leaf physiological traits. Epistasis uncovered 83 pairwise interactions among these traits, revealing Cd-responsive lncRNA-mediated genetic networks for photosynthesis and leaf physiology in P. tomentosa. We focused on the roles of two Cd-responsive lncRNA–gene pairs, MSTRG.22608.1–PtoMYB73 and MSTRG.5634.1–PtoMYB27, in Cd tolerance of Populus, and detected insertions/deletions within lncRNAs as polymorphisms driving target gene expression. Genotype analysis of lncRNAs and heterologous overexpression of PtoMYB73 and PtoMYB27 in Arabidopsis indicated their effects on enhancing Cd tolerance, photosynthetic rate, and leaf growth, and the potential interaction mechanisms of PtoMYB73 with abiotic stresses. Our study identifies the genetic basis for the response of Populus to Cd treatment, facilitating genetic improvement of Cd tolerance in trees.

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Worldwide genetic variation in dopamine and serotonin pathway genes: Implications for association studies

American Journal of Medical Genetics Part B Neuropsychiatric Genetics ◽

10.1002/ajmg.b.30717 ◽

2008 ◽

Vol 147B (7) ◽

pp. 1070-1075 ◽

Cited By ~ 14

Author(s):

Michelle Gardner ◽

Jaume Bertranpetit ◽

David Comas

Keyword(s):

Genetic Variation ◽

Association Studies ◽

Serotonin Pathway

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Epistatic Interaction between Fibrinogen alpha and gamma Genes and Factor V Leiden in Children with Venous Thrombosis: Results from a Family-Based Association Study.

Blood ◽

10.1182/blood.v110.11.1640.1640 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1640-1640

Author(s):

Ulrike Nowak-Gottl ◽

Hartmut Weiler ◽

Tanja Seehafer ◽

Sabine Thedieck ◽

Monika Stoll

Keyword(s):

Genetic Variation ◽

Epistatic Interaction ◽

Association Studies ◽

Factor V Leiden ◽

Complex Nature ◽

Factor V ◽

Nucleotide Polymorphisms ◽

Permutation Testing ◽

Factor V Leiden Mutation ◽

Family Based

Abstract Background: Fibrinogen, the precursor of fibrin, is an essential component of the hemostatic system. A previous large case-control study showed that genetic variation in the fibrinogen gamma gene (FGG) increased the risk for VT in adults. Here we investigated the association of haplotypes comprising the fibrinogen alpha (FGA) and gamma (FGG) genes, carriership of the Factor V Leiden mutation and risk for VT in a large family-based study sample for pediatric VT. Methods: We genotyped 188 pediatric VT families for seven single nucleotide polymorphisms (SNPs) (rs6050, rs2070016, rs2070014 and rs2070011, rs1049636, rs2066861, rs2066860) as well as the G1691A Factor V Leiden (FV) polymorphism. Association was assessed using the Transmission Disequilibrium Test (TDT) and corrected for multiple testing using permutation testing as implemented in HAPLOVIEW. Interaction between FV and FGA and FGG, respectively, was assessed by TDT in families stratified for presence or absence of the FV mutation in the affected child. Results: rs6050, rs2070016, rs2070014 and rs2070011 located in the FGA gene are in tight linkage disequilibrium (LD) and define 5 common haplotypes (HT) and are linked with the neighboring FGG gene (q= 0.91). rs1049636, rs2066861, rs2066860 located in FGG are in tight LD and define 4 HTs. HTs in both, FGA and FGG are significantly overtransmitted from parents to affected offspring (FGA: HT1 (AACT), HT frequency 0.32, T:U 62: 32, p=0.0025; FGG: HT2 (ATC), HT frequency 0.32, T:U 60:32, p=0.0035). When stratifying for FV status, it became apparent that the association between FGA and FGG and VT was more pronounced in FV-negative families (FGA, HT1, T:U 55:24, p=0.0006; FGG, HT2, T:U 55:24, p=0.0005), while absent in FV-positive families. Conclusion: Our results indicate that genetic variation in FGA and FGG are risk factors for VT in children, and further that an epistatic interaction between FGA/FGG and FV Leiden influences the risk of FGG and FGA on pediatric VT. Our study highlights the complex nature of VT and the necessity to evaluate gene-gene interactions in association studies of complex, polygenic diseases.

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