genome wide association study

Top PDF genome wide association study:

Lecture 7: Genome-wide Association Study

Lecture 7: Genome-wide Association Study

Genome-Wide Association Study (GWAS) — 27/37 — GWAS: independent single-variant tests across all genome-wide variants • Quality control (QC) of the study dataset • Choose a model/test for the phenotype of interest (e.g., linear regression model for quantitative traits, logistic regression model for dichotomous traits, other

38 Read more

A genome-wide association study of anorexia nervosa.

A genome-wide association study of anorexia nervosa.

Title: A genome-wide association study of anorexia nervosa. Authors: Boraska V, Franklin CS, Floyd JA, Thornton LM, Huckins LM, Southam L, Rayner NW, Tachmazidou I, Klump KL, Treasure J, Lewis CM, Schmidt U, Tozzi F, Kiezebrink K, Hebebrand J, Gorwood P, Adan RA, Kas MJ, Favaro A, Santonastaso P, Fernández-Aranda F, Gratacos M, Rybakowski F, Dmitrzak-Weglarz M, Kaprio J, Keski-Rahkonen A, Raevuori A, Van Furth EF, Slof-Op 't Landt MC, Hudson JI, Reichborn- Kjennerud T, Knudsen GP, Monteleone P, Kaplan AS, Karwautz A, Hakonarson H, Berrettini WH, Guo Y, Li D, Schork NJ, Komaki G, Ando T, Inoko H, Esko T, Fischer K, Männik K, Metspalu A, Baker JH, Cone RD, Dackor J, DeSocio JE, Hilliard CE, O'Toole JK, Pantel J, Szatkiewicz JP, Taico C, Zerwas S, Trace SE, Davis OS, Helder S, Bühren K,
Show more

27 Read more

A genome-wide association study of bronchodilator response in asthmatics

A genome-wide association study of bronchodilator response in asthmatics

(CRHR)-2 locus, 10 and the adenylyl cyclase type 9 (AC9) gene. 11 A recent genome-wide association study (GWAS) of BDR by our group identified a functional variant in the serine- rich 2-like (SPATS2L) gene, albeit the mechanism by which it regulates BDR remains unknown. 12 In this manuscript, we expand on the previous literature by using a novel approach to identify genetic associations with BDR (defined by a change in lung function) whereby we apply five statistical models in a GWAS of this drug response phenotype to decrease the likelihood of false positive associations. Novel aspects of the current GWAS include use of genetic data from the parents of asthmatics in a family-based test, which is more robust against population stratification, as well as analysis of 11 BDR measures for each subject taken over a four year period in addition to BDR at randomization (taken upon entry into the clinical trial). Moreover, we considered both additive and recessive
Show more

18 Read more

Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis.

Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis.

Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome- wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish–Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p < 10 −5 ) were observed in the GWAS. In the replication population, three SNPs
Show more

9 Read more

A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism

A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism

Abstract Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism. Our objective was to use nicotine metabo- lite ratio (NMR), an established biomarker of nicotine metabolism rate, in a genome-wide association study (GWAS) to identify novel genetic variants influencing nicotine metabo- lism. A heritability estimate of 0.81 (95% CI 0.70 –0.88) was obtained for NMR using mono- zygotic and dizygotic twins of the FinnTwin cohort. We performed a GWAS in cotinine- verified current smokers of three Finnish cohorts (FinnTwin, Young Finns Study, FIN- RISK2007), followed by a meta-analysis of 1518 subjects, and annotated the genome-wide significant SNPs with methylation quantitative loci (meQTL) analyses. We detected associ- ation on 19q13 with 719 SNPs exceeding genome-wide significance within a 4.2 Mb region. The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Other interesting genes with genome-wide signifi- cant signals included CYP2B6, CYP2A7, EGLN2, and NUMBL. Conditional analyses revealed three independent signals on 19q13, all located within or in the immediate vicinity of CYP2A6. A genetic risk score constructed using the independent signals showed associ- ation with smoking quantity (p = 0.0019) in two independent Finnish samples. Our meQTL results showed that methylation values of 16 CpG sites within the region are affected by genotypes of the genome-wide significant SNPs, and according to causal inference test, for some of the SNPs the effect on NMR is mediated through methylation. To our knowledge, this is the first GWAS on NMR. Our results enclose three independent novel signals on 19q13.2. The detected CYP2A6 variants explain a strikingly large fraction of variance (up to a11111
Show more

23 Read more

Semantically enabling a genome-wide association study database

Semantically enabling a genome-wide association study database

16. Hughes LM, Bao J, Hu ZL, Honavar V, Reecy JM: Animal trait ontology: The importance and usefulness of a unified trait vocabulary for animal species. J Anim Sci 2008, 86(6):1485 – 1491. 17. Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, Papadakis K, Voight BF, Scott LJ, Zhang F, Farrall M, Tanaka T, Wallace C, Chambers JC, Khaw KT, Nilsson P, van der Harst P, Polidoro S, Grobbee DE, Onland-Moret NC, Bots ML, Wain LV, Elliott KS, Teumer A, Luan J, Lucas G, et al: Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 2009, 41(6):666 – 676.
Show more

16 Read more

Genome-Wide Association Study of Parity in Bangladeshi Women

Genome-Wide Association Study of Parity in Bangladeshi Women

As investigation of this hypothesis is novel, the findings presented here offer some insight into genetic variation and parity. Although our null GWAS doesn ’t rule out substantial herita- bility as it’s possible that many very weak effects could account for parity variation, overall, our findings are consistent with a low heritability of phenotypic variability for parity. In summary, our genome-wide association study of number of pregnancies and number of children in Ban- gladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of specific SNPs on chromo- somes 4, 5 and 6 in their analysis.
Show more

13 Read more

Genome wide association study of Alzheimer's disease with psychotic symptoms

Genome wide association study of Alzheimer's disease with psychotic symptoms

Genome-wide Association Study of Alzheimer’s disease with Psychotic Symptoms Paul Hollingworth 1,16 , Robert A. Sweet 2,3,4,16,* , Rebecca Sims 1,16 , Denise Harold 1 , Giancarlo Russo 1 , Richard Abraham 1 , Alexandra Stretton 1 , Nicola Jones 1 , Amy Gerrish 1 , Jade Chapman 1 , Dobril Ivanov 1 , Valentina Moskvina 1 , Simon Lovestone 5 , Petroula Priotsi 5 , Michelle Lupton 5 , Carol Brayne 6 , Michael Gill 7 , Brian Lawlor 7 , Aoibhinn Lynch 7 , David Craig 8 , Bernadette McGuinness 8 , Janet Johnston 8 , Clive Holmes 9 , Gill Livingston 10 , Nicholas J. Bass 10 , Hugh Gurling 10 , Andrew McQuillin 10 , GERAD Consortium11, the National Institute on Aging Late-Onset Alzheimer’s Disease Family Study Group12, Peter Holmans 1 , Lesley Jones 1 , Bernie Devlin 2 , Lambertus Klei 2 , M. Michael Barmada 14 , F.
Show more

19 Read more

TDT for Human QTL Mapping and Genome - Wide Association Study

TDT for Human QTL Mapping and Genome - Wide Association Study

Furthermore, though the TDT approach used for gene mapping at multi loci has been studied by a number of researchers recently, the application of TDT to genome- wide association study has not been tackled so far. Since the rapid improvement in SNP genotyping technology makes it possible to find the genetic contributions to common disease, in this thesis we develop a generalized TDT by a penalized logistic model to extend the TDT to genome-wide association study. By virtue of this model, we convert the linkage study for gene mapping to variable selection problem. A two-step method which combines the e fficient algorithm for variables selection with a new criterion for model selection is proposed. In the simulation study, by comparing the false discovery rate and positive selection rate with the Bonferroni-type multiple-comparison approach, it is demonstrated that our method is valid and e fficient.
Show more

118 Read more

A Genome-Wide Association Study for Regulators of Micronucleus Formation in Mice

A Genome-Wide Association Study for Regulators of Micronucleus Formation in Mice

ABSTRACT In mammals the regulation of genomic instability plays a key role in tumor suppression and also controls genome plasticity, which is important for recombination during the processes of immunity and meiosis. Most studies to identify regulators of genomic instability have been performed in cells in culture or in systems that report on gross rearrangements of the genome, yet subtle differences in the level of genomic instability can contribute to whole organism phenotypes such as tumor predisposition. Here we performed a genome-wide association study in a population of 1379 outbred Crl:CFW(SW)-US_P08 mice to dissect the genetic landscape of micronucleus formation, a biomarker of chromosomal breaks, whole chromosome loss, and extranuclear DNA. Variation in micronucleus levels is a complex trait with a genome- wide heritability of 53.1%. We identify seven loci influencing micronucleus formation (false discovery rate ,5%), and define candidate genes at each locus. Intriguingly at several loci we find evidence for sexual dimorphism in micronucleus formation, with a locus on chromosome 11 being specific to males.
Show more

12 Read more

A genome-wide association study for corneal astigmatism: The CREAM Consortium

A genome-wide association study for corneal astigmatism: The CREAM Consortium

17. Li Q, Wojciechowski R, Simpson CL, Hysi PG, Verhoeven VJ, Ikram MK, Hohn R, Vitart V, Hewitt AW, Oexle K, Makela KM, MacGregor S, Pirastu M, Fan Q, Cheng CY, St Pourcain B, McMahon G, Kemp JP, Northstone K, Rahi JS, Cumberland PM, Martin NG, Sanfilippo PG, Lu Y, Wang YX, Hayward C, Polasek O, Campbell H, Bencic G, Wright AF, Wedenoja J, Zeller T, Schillert A, Mirshahi A, Lackner K, Yip SP, Yap MK, Ried JS, Gieger C, Murgia F, Wilson JF, Fleck B, Yazar S, Vingerling JR, Hofman A, Uitterlinden A, Rivadeneira F, Amin N, Karssen L, Oostra BA, Zhou X, Teo YY, Tai ES, Vithana E, Barathi V, Zheng Y, Siantar RG, Neelam K, Shin Y, Lam J, Yonova-Doing E, Venturini C, Hosseini SM, Wong HS, Lehtimaki T, Kahonen M, Raita- kari O, Timpson NJ, Evans DM, Khor CC, Aung T, Young TL, Mitchell P, Klein B, van Duijn CM, Meitinger T, Jonas JB, Baird PN, Mackey DA, Wong TY, Saw SM, Parssinen O, Stambolian D, Hammond CJ, Klaver CC, Williams C, Paterson AD, Bailey-Wilson JE, Guggenheim JA. Cream Consortium. Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium. Hum Genet 2015; 134:131-46. .
Show more

17 Read more

Genome-Wide Association Study for Mid-Salt Tolerance in Rice

Genome-Wide Association Study for Mid-Salt Tolerance in Rice

ABSTRACT Salt stress is one of the environmental constraints that affect crop cultivation worldwide, since more than 800 Mha of land throughout the world suffer from salinization problems. Among cereals, rice (Oryza sativa L.) is one of the most sensitive to salt stress, although cultivars can differ in their response to salinity. In Europe, due to scarce water availability and the rise in sea levels, there is a clear tendency toward salinization in the river deltas where rice is grown. Thus, the identification of rice cultivars tolerant to salt stress and the dissection of salt stress tolerance mechanisms are of high interest for European rice breeding. Plant response to salt stress is a complex trait, depending on the combination of many genes and metabolic pathways, and thus difficult to control and engineer. Exploiting natural variation occurring in worldwide genotypes may be a powerful approach to discover new traits to tolerate high salinity conditions. In this context, a phenotyping activity has been performed to study the natural variation of a worldwide japonica rice collection in response to mid-salt stress. A greenhouse experiment was carried out on 281 japonica rice cultivars subjected to salt stress and the measurement of physiological traits (i.e. seedlings emergence rate, plant growth, chlorophyll fluorescence, flowering delay) was assessed. A genome wide association study (GWAS) highlighted the presence of significant loci involved in salt tolerance. Analysis of candidate genes significantly associated to these loci is in progress.
Show more

8 Read more

A genome-wide association study on medulloblastoma.

A genome-wide association study on medulloblastoma.

carriers of the risk allele had a more than two-fold increased risk. Our findings were not statistically significant when using the p value threshold p < 5 × 10 –8 to correct for mul- tiple comparisons. Although a stringent p-value threshold is required in GWAS to reduce the presence of false posi- tive findings, strict Bonferroni correction may be considered overly conservative due to linkage disequilibrium between many genetic variants. Twelve variants with evidence for associations in the initial analyses were investigated in an additional cohort. One of these SNPs, located in 18p11.23 (PTPRM) showed suggestive evidence for an association with medulloblastoma risk also in the validation cohort. The PTPRM gene product is a receptor-type protein tyros- ine phosphatase that mediates cell–cell adhesion. Altered expression, mutations, or aberrant methylation of PTPRM have been described in different malignancies, including glioblastoma [ 9 ]. The role of PTPRM in medulloblastoma is, to our knowledge, unknown, but it is interesting to note that the PTPRM protein has been shown to interact with beta- catenin [ 10 ]. Beta-catenin is a central part of the Wnt signal- ing pathway and is encoded by the gene CTNNB1, which is frequently mutated in WNT medulloblastoma [ 5 ]. However, only about 10% of all medulloblastoma tumors belong to the WNT subgroup [ 5 ], and this subgroup is therefore rep- resented by few patients in the study cohort. Investigation of
Show more

8 Read more

A Genome Wide Association Study for  Longevity in Cattle

A Genome Wide Association Study for Longevity in Cattle

Genomic associations for longevity were studied using deregressed breeding values from 4887 Fleckvieh bulls and 33,556 SNPs with a single SNP approach. A correction for population structure using 103 eigenvectors led to the removal of many false positive SNPs and identified relevant regions on the cattle genome as associated with longevity. Different numbers of SNPs were selected, depending on the used methodology. The Bonferroni threshold selected 2 significant SNPs, the local false discovery rate 14 and the q-value threshold (0.05) a total of 67 important SNPs. It seems that the Bonferroni is too conservative yet the q-values with a threshold of 0.05 too liberal. The best number of selected SNPs is likely between these two extremes, pointing towards the local false discovery method as a possible compromise. The most notable associations and corresponding genes from eight chromosomes were described in this paper. The most interesting genes were SYT10 located on chromosome 5, ADAMTS3 on chromosome 6, NTRK2 on chromosome 8 and DERL1 and SNTG1 on chromosome 14. Some of the associated regions contained genes previously associated with fertility in cattle. As fertility is one of the most important traits contributing to the culling of animals, longevity is highly influenced by poor reproductive performance. Several signals, including the highest significant signal found on chromosome 14, were located in genomic regions with very few identified genes. This allows us to speculate that there might be other genes or pathways with an influence on cattle longevity which is not yet specified. This, alongside the great economic impact of longevity on the cattle industry, is a clear stimulant for more genomic research in this field.
Show more

10 Read more

Progress of genome wide association study in domestic animals

Progress of genome wide association study in domestic animals

Conclusions In summary, there was a great progress of GWAS in do- mestic animals and some genes for economically import- ant traits have been identified. However, the main problem lies in the inconsistencies among the results of these GWAS reports for the same trait, which may be mainly attributed to many aspects such as population size, density of the markers (SNPs), population genetic structure, choice of statistical models, as well as type I and II errors. To achieve the accurate estimation of SNP effects on traits of interest in a GWAS, larger population size and higher density of the markers (SNPs) were required. Currently, SNP chips were widely applied in GWAS and enhanced the identification of QTL for traits of interest in domestic animals. Compared with SNP chips, sequencing could provide nearly all information about the variations, including SNP, copy number vari- ation (CNV) and the deletion/insertion, et al., on the whole genome in detected population. Along with the reduction in sequencing cost, it is possible that all indivi- duals in the tested populations might be sequenced and genotyped and GWAS might be carried out in this plat- form then. In the future, GWAS in domestic animals will focus on the identification of causative mutations for economically important traits. The findings will inev- itably facilitate the understanding of the genetic archi- tecture of complex traits in domestic animals and practical improving the breeding programmes.
Show more

10 Read more

Genome wide association study for multiple phenotype analysis

Genome wide association study for multiple phenotype analysis

San Diego, CA, USA. 4 - 8 March 2017 Abstract Genome-wide association studies often collect multiple phenotypes for complex diseases. Multivariate joint analyses have higher power to detect genetic variants compared with the marginal analysis of each phenotype and are also able to identify loci with pleiotropic effects. We extend the unified score-based association test to incorporate family structure, apply different approaches to analyze multiple traits in GAW20 real samples, and compare the results. Through simulation studies, we confirm that the Type I error rate of the pedigree-based unified score association test is appropriately controlled. In marginalanalysis of triglyceride levels, we found 1 subgenome-wide significant variant on chromosome 6. Joint analyses identified several suggestive genome-wide significant signals, with the pedigree-based unified score association test yielding the greatest number of significant results.
Show more

6 Read more

A genome-wide association study in multiple system atrophy

A genome-wide association study in multiple system atrophy

We were unable to replicate the previously reported association of variants at the SNCA. 8,22,23 A Korean study was also unable to reproduce the association indicating possible differences between populations or an actual null result. 32 The previously associated SNP rs11931074 has considerable variation in fre- quency among different populations. The reported risk allele has a frequency of about 7%–8% in our different European controls and in the European HapMap data. 33 In contrast, the same allele is much more abun- dant in Asian and African populations (e.g., 58% in Japanese and 68% in Yorubans). Our study attempts to account for both interpopulation and intrapopula- tion heterogeneity through principal component anal- ysis, and interpopulation heterogeneity of SNCA is a plausible explanation for the previous findings.
Show more

10 Read more

Genome-wide association study of male sexual orientation

Genome-wide association study of male sexual orientation

This work was supported by NICHD: the Eunice Kennedy Shriver National Institute of Child Health and Human Development (A.R.S., grant no. R01HD041563 for the Affymetrix 5.0 genotyped sample and A.R.S. and E.R.M., grant no. R21HD080410 for various analyses), and by the Molecular Genetics of Schizophrenia (MGS) Collaboration for the Affymetrix 6.0 genotyped sample. The MGS Collaboration includes P.V.G., A.R.S., and J.D., in addition to the individuals in the MGS Collaboration group author list. MGS was mainly supported by R01MH059571, R01MH081800, and U01MH079469 (to P.V.G.), and other NIH grants for other MGS sites (R01MH067257 to N.G.B., R01MH059588 to B.J.M., R01MH059565 to R.F., R01MH059587 to F.A., R01MH060870 to W.F.B., R01MH059566 to D.W.B., R01MH059586 to J.M.S., R01MH061675 to D.F.L., R01MH060879 to C.R.C., U01MH046276 to C.R.C., and U01MH079470 to D.F.L). We thank the men for their participation, Timothy F. Murphy for his work on the community advisory board and study website, and Besiana Liti for technical assistance.
Show more

6 Read more

Genome-wide association study in Guillain-Barré syndrome

Genome-wide association study in Guillain-Barré syndrome

Given the previous reported associations of GBS with HLA alleles, we investigated these and the MHC region more closely. A total of 8,961 SNPs within the MHC region, HLA alleles and their composite amino acids were imputed with SNP2HLA. We excluded markers with r 2 < 0.5 and samples with unreliable imputed data, leaving 8,597 SNPs and 821 individuals for further logistic regression analysis. No MHC SNPs or imputed HLA alleles reached suggestive significance levels for association with GBS. The strongest SNP association with rs6928738 (P = 2.19 × 10 −4 ; within the MHC Class I region, nearest gene being the hypothetical gene, LOC646570). The strongest HLA association was with HLA-A*3001 (P = 1.29 × 10 −2 ). A recent
Show more

31 Read more

Genome-wide association study of antisocial personality disorder

Genome-wide association study of antisocial personality disorder

identical genotypes as the GWAS genotyping with 499% concordance between the two methods. In a post hoc repeat GWAS analysis, including the CRIME subjects and GenMets controls, the results were consistent with the original analysis. This also indicated that had there been discrepancy with the Corogene control sample genotypes of the eight SNPs in the GWAS, this would have shown in the repeat analysis results. In spite of intensive QC, spurious associations may occur. We considered the top variant (rs6462756, near SDK1 gene) of the analysis of males and females combined as a plausible false positive, as it was the only signal from that genomic region (7p22.2), where the SNP density was not particularly sparse, rather to the contrary, relatively dense (35 SNPs per 100 kb, compared with chr 7p average 21 SNPs per 100 kb and the nearby 500 kb average 25 SNPs per 100 kb), and thus, it was not selected to the regenotyping nor to the replication study.
Show more

10 Read more

Show all 10000 documents...