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

2006 ◽  
Vol 17 (1) ◽  
pp. 88-95 ◽  
Author(s):  
S. Eyheramendy ◽  
J. Marchini ◽  
G. McVean ◽  
S. Myers ◽  
P. Donnelly
Keyword(s):  
Genetic Variation ◽  
Association Studies ◽  
Model Based

scholarly journals Rapid Epistatic Mixed Model Association Studies by Controlling Multiple Polygenic Effects

2020 ◽  
Author(s):  
Dan Wang ◽  
Hui Tang ◽  
Jian-Feng Liu ◽  
Shizhong Xu ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Population Size ◽  
Computational Efficiency ◽  
Mixed Model ◽  
Association Studies ◽  
Approximate Algorithm ◽  
Source Codes ◽  
Model Based ◽  
Pairwise Interactions ◽  
Genome Wide ◽  
Model Algorithm

SummaryWe have developed a rapid mixed model algorithm for exhaustive genome-wide epistatic association analysis by controlling multiple polygenic effects. Our model can simultaneously handle additive by additive epistasis, dominance by dominance epistasis and additive by dominance epistasis, and account for intrasubject fluctuations due to individuals with repeated records. Furthermore, we suggest a simple but efficient approximate algorithm, which allows examination of all pairwise interactions in a remarkably fast manner of linear with population size. Application to publicly available yeast and human data has showed that our mixed model-based method has similar performance with simple linear model-based Plink on computational efficiency. It took less than 40 hours for the pairwise analysis of 5,000 individuals genotyped with roughly 350,000 SNPs with five threads on Intel Xeon E5 2.6GHz CPU.Availability and implementationSource codes are freely available at https://github.com/chaoning/GMAT.

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

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.

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

Circulation ◽  
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.

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

Genes ◽  
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.

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 ◽  
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.

scholarly journals Mixture model-based association analysis with case-control data in genome wide association studies

2017 ◽  
Vol 16 (3) ◽  
Author(s):  
Fadhaa Ali ◽  
Jian Zhang
Keyword(s):  
Mixture Model ◽  
Multiple Testing ◽  
Hypothesis Test ◽  
Association Studies ◽  
Real Data ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Model Based ◽  
Genome Wide ◽  
The Individual

AbstractMultilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated disease penetrances. A theoretical justification of the above model is provided. Furthermore, we introduce a hypothesis test for haplotype inheritance patterns which underpin this model. The performance of the proposed approach is evaluated by simulations and real data analysis. The results show that the proposed approach outperforms an existing multiple testing method.

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