Effect of Population Stratification on False Positive Rates of Population‐Based Association Analyses of Quantitative Traits

Haldar, Tanushree; Ghosh, Saurabh

doi:10.1111/j.1469-1809.2012.00708.x

Cited by 22 publications

(20 citation statements)

References 11 publications

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“…Differences in allele frequencies between subpopulations of admixed populations can lead to false association in a GWAS [41]. In order to determine whether stratification exists in our study population, a principle component analysis (PCA) was performed by GCTA 1.24 [42] and results were visualized by R 3.3.1 [43].…”

Section: Methodsmentioning

confidence: 99%

Genome-wide association study of Mycobacterium avium subspecies Paratuberculosis infection in Chinese Holstein

et al. 2018

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BackgroundParatuberculosis is a contagious, chronic and enteric disease in ruminants, which is caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection, resulting in enormous economic losses worldwide. There is currently no effective cure for MAP infection or a vaccine, it is thus important to explore the genetic variants that contribute to host susceptibility to infection by MAP, which may provide a better understanding of the mechanisms of paratuberculosis and benefit animal genetic improvement. Herein we performed a genome-wide association study (GWAS) to identify genomic regions and candidate genes associated with susceptibility to MAP infection in dairy cattle.ResultsUsing Illumina Bovine 50 K (54,609 SNPs) and GeneSeek HD (138,893 SNPs) chips, two analytical approaches were performed, GRAMMAR-GC and ROADTRIPS in 937 Chinese Holstein cows, among which individuals genotyped by the 50 K chip were imputed to HD SNPs with Beagle software. Consequently, 15 and 11 significant SNPs (P < 5 × 10− 5) were identified with GRAMMAR-GC and ROADTDRIPS, respectively. A total of 10 functional genes were in proximity to (i.e., within 1 Mb) these SNPs, including IL4, IL5, IL13, IRF1, MyD88, PACSIN1, DEF6, TDP2, ZAP70 and CSF2. Functional enrichment analysis showed that these genes were involved in immune related pathways, such as interleukin, T cell receptor signaling pathways and inflammatory bowel disease (IBD), implying their potential associations with susceptibility to MAP infection. In addition, by examining the publicly available cattle QTLdb, a previous QTL for MAP was found to be overlapped with one of regions detected currently at 32.5 Mb on BTA23, where the TDP2 gene was anchored.ConclusionsIn conclusion, we identified 26 SNPs located on 15 chromosomes in the Chinese Holstein population using two GWAS strategies with high density SNPs. Integrated analysis of GWAS, biological functions and the reported QTL information helps to detect positional candidate genes and the identification of regions associated with susceptibility to MAP traits in dairy cattle.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5385-3) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Genome-wide association study of Mycobacterium avium subspecies Paratuberculosis infection in Chinese Holstein

et al. 2018

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“…Population strati cation can result in spurious association ndings in a GWAS [29]. Thus, we calculated genomic in ation factor (λ) and also depicted quantile-quantile (Q-Q) plot to assess strati cation in our study population using GENABEL and qqman packages in R 3.6.0.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Studies for Immunoglobulin Concentrations in Colostrum and Serum in Chinese Holstein

Lin

Liu³

et al. 2020

Preprint

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BackgroundThe early death and health problems of calves caused substantial economic losses in dairy industry. As the immune system has not been fully developed in the neonates, transport of passive immune substance such as immunoglobulins (Ig) from mothers to newborn calves is essential in protecting neonates from infections in their early life. Therefore, concentrations of immunoglobulins in the colostrum and serum of dairy cows are critical traits when estimating potential disease resistance of its offspring. ResultsColostrum, blood and hair follicle samples were collected from the 620 Chinese Holstein cows within 24 hours after calving. The concentration of total IgG, IgG1, IgG2, IgA and IgM in both colostrum and serum were detected via ELISA methods. With GCTA software, genome-wide association studies (GWASs) were performed with 88,934 SNPs genotyped by using Illumina 50K (54,609 SNPs) and GeneSeek 150K (140,668 SNPs) chips in which 50K chip were imputed to 150K SNPs with BEAGLE. As a result, 20, 1 and 4 significant SNPs were detected associated with the concentrations of IgG2, IgA and IgM at genome-wide level (P < 3.16E–6); 11, 11, 35, 11 and 10 significant SNPs were identified associated with total IgG, IgG1, IgG2, IgA and IgM at suggestive level (P < 6.32E–5). Such SNPs were located in or proximate to (±1 Mb) 1,083 genes, which were functionally implicated in biological processes and pathways, such as immune response, negative regulation of immunoglobulin secretion, Fc-epsilon receptor and NF-kappaB signaling pathways. By combining the biological functions and the known QTL data for immune traits in bovine, 21 promising candidate functional genes were identified for immunoglobulins concentrations in colostrum and serum in dairy cattle, they were ABR, TIMM22, CRK, MYO1C, RILP, SERPINF2, AKT1, BCL11B, HHIPL1, DYNC1H1, HSP90AA1, TRAF3, KLC1, IL6, PYCARD, ITGAM, TGFB1I1, GUSB, CRCP, RABGEF1 and SBDS.ConclusionsIn this study, we identified 21 candidate genes related to concentrations of immunoglobulins in colostrum and serum in dairy cattle by performing GWASs. Our findings provide a groundwork for unraveling the key genes and causal mutations affecting immunoglobulins levels in colostrum and important information for genetic improvement of such traits in dairy cattle.

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“…It is important to note that the case-control approach has an inherent potential for false-positive results due to differences in population stratification between cases and control subjects [30]. However, as both asthmatic patients and controls were in Hardy-Weinberg equilibrium with MIF-173G/C genotypes’ distribution, and since we studied only one locus in an exclusively Egyptian population, problems associated with population stratification might be of little importance, with a limited effect on the present study.…”

Section: Discussionmentioning

confidence: 99%

Association of macrophage migration inhibitory factor promoter polymorphism –173G/C with susceptibility to childhood asthma

El-Adly¹,

Kamal²,

Selim³

et al. 2016

cejoi

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IntroductionMacrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in the pathogenesis of asthma. Polymorphisms associated with inflammatory diseases exist in the promoter region of MIF, which alter its expression. We aimed to study the association of MIF promoter polymorphism –173G/C with childhood asthma.Material and methodsIn this case-control study, we recruited 60 pediatric patients with bronchial asthma and 90 age- and sex-matched healthy controls. MIF-173G/C was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsGenotype distribution between cases and healthy controls was statistically evaluated. Our results revealed that the frequency of the MIF-173C allele was significantly higher in children with asthma than in the control group (p = 0.002, odds ratio [OR] = 3.61, 95% confidence interval [CI] = 1.63-7.97). The frequency of the MIF-173CC genotype was higher in the asthmatic children than in the controls (p = 0.028, OR = 6.24, 95% CI = 1.24-31.29). Comparing carriage of the MIF-173C allele in pediatric patients with asthma with that observed in healthy controls (GC + CC vs. GG) revealed a positive association with the disease (p = 0.019, OR = 3.12, 95% CI = 1.22-7.99).ConclusionsThese results suggest that MIF-173G/C polymorphism confers an increased risk of susceptibility to the development of childhood asthma in an Egyptian population.

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Effect of Population Stratification on False Positive Rates of Population‐Based Association Analyses of Quantitative Traits

Cited by 22 publications

References 11 publications

Genome-wide association study of Mycobacterium avium subspecies Paratuberculosis infection in Chinese Holstein

Genome-wide association study of Mycobacterium avium subspecies Paratuberculosis infection in Chinese Holstein

Genome-Wide Association Studies for Immunoglobulin Concentrations in Colostrum and Serum in Chinese Holstein

Association of macrophage migration inhibitory factor promoter polymorphism –173G/C with susceptibility to childhood asthma

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