scholarly journals Population Admixture May Appear to Mask, Change or Reverse Genetic Effects of Genes Underlying Complex Traits

Genetics ◽  
2001 ◽  
Vol 159 (3) ◽  
pp. 1319-1323
Author(s):  
Hong-Wen Deng
Keyword(s):  
Population Genetics ◽  
False Positive ◽  
Complex Traits ◽  
Association Studies ◽  
Genetic Effects ◽  
Population Admixture ◽  
Reverse Genetic ◽  
Positive Identification ◽  
False Positive Identification

Abstract Association studies using random population samples are increasingly being applied in the identification and inference of genetic effects of genes underlying complex traits. It is well recognized that population admixture may yield false-positive identification of genetic effects for complex traits. However, it is less well appreciated that population admixture can appear to mask, change, or reverse true genetic effects for genes underlying complex traits. By employing a simple population genetics model, we explore the effects and the conditions of population admixture in masking, changing, or even reversing true genetic effects of genes underlying complex traits.

scholarly journals Population Admixture: Detection by Hardy-Weinberg Test and Its Quantitative Effects on Linkage-Disequilibrium Methods for Localizing Genes Underlying Complex Traits

Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 885-897 ◽  
Author(s):  
Hong-Wen Deng ◽  
Wei-Min Chen ◽  
Robert R Recker
Keyword(s):  
Linkage Disequilibrium ◽  
Error Rate ◽  
Population Differentiation ◽  
False Positive ◽  
Complex Traits ◽  
Type I Error ◽  
Association Studies ◽  
Type I ◽  
Population Admixture ◽  
Random Samples

Abstract In association studies searching for genes underlying complex traits, the results are often inconsistent, and population admixture has been recognized qualitatively as one major potential cause. Hardy-Weinberg equilibrium (HWE) is often employed to test for population admixture; however, its power is generally unknown. Through analytical and simulation approaches, we quantify the power of the HWE test for population admixture and the effects of population admixture on increasing the type I error rate of association studies under various scenarios of population differentiation and admixture. We found that (1) the power of the HWE test for detecting population admixture is usually small; (2) population admixture seriously elevates type I error rate for detecting genes underlying complex traits, the extent of which depends on the degrees of population differentiation and admixture; (3) HWE testing for population admixture should be performed with random samples or only with controls at the candidate genes, or the test can be performed for combined samples of cases and controls at marker loci that are not linked to the disease; (4) testing HWE for population admixture generally reduces false positive association findings of genes underlying complex traits but the effect is small; and (5) with population admixture, a linkage disequilibrium method that employs cases only is more robust and yields many fewer false positive findings than conventional case-control analyses. Therefore, unless random samples are carefully selected from one homogeneous population, admixture is always a legitimate concern for positive findings in association studies except for the analyses that deliberately control population admixture.

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.

False-positive identification ofEscherichia coliin treated municipal wastewater and wastewater-irrigated soils

2011 ◽  
Vol 57 (10) ◽  
pp. 775-784 ◽  
Author(s):  
Jean E.T. McLain ◽  
Channah M. Rock ◽  
Kathleen Lohse ◽  
James Walworth
Keyword(s):  
Water Quality ◽  
False Positive ◽  
Municipal Wastewater ◽  
Inorganic Compounds ◽  
Treated Wastewater ◽  
Technical Literature ◽  
E Coli ◽  
Positive Identification ◽  
False Positive Identification ◽  
Irrigated Soils

The increasing use of treated wastewater for irrigation heightens the importance of accurate monitoring of water quality. Chromogenic media, because they are easy to use and provide rapid results, are often used for detection of Escherichia coli in environmental samples, but unique levels of organic and inorganic compounds alter the chemistry of treated wastewater, potentially hindering the accurate performance of chromogenic media. We used MI agar and molecular confirmatory methods to assess false-positive identification of E. coli in treated wastewater samples collected from municipal utilities, an irrigation holding pond, irrigated soils, and in samples collected from storm flows destined for groundwater recharge. False-positive rates in storm flows (4.0%) agreed closely with USEPA technical literature but were higher in samples from the pond, soils, and treatment facilities (33.3%, 38.0%, and 48.8%, respectively). Sequencing of false-positive isolates confirmed that most were, like E. coli, of the family Enterobacteriaceae, and many of the false-positive isolates were reported to produce the β-d-glucuronidase enzyme targeted by MI agar. False-positive identification rates were inversely related to air temperature, suggesting that seasonal variations in water quality influence E. coli identification. Knowledge of factors contributing to failure of chromogenic media will lead to manufacturer enhancements in media quality and performance and will ultimately increase the accuracy of future water quality monitoring programs.

False Positive Identification

1978 ◽  
Vol 18 (4) ◽  
pp. 255-262 ◽  
Author(s):  
E. Linden Hilgendorf ◽  
B. L. Irving
Keyword(s):  
False Positive ◽  
Waiting Room ◽  
Positive Identification ◽  
False Positive Identification ◽  
High Level

This paper reports the results of a simulation of an identification parade using recommended procedures. The parade was held three days after subjects had been incidental observers of a man in a waiting room. The Parade included ‘a suspect’ who was not the man Previously seen. Of the 68 subjects, 21 made a false Positive identification on the parade, including 6 who made an identification with a high level of certainty. All these 6 high certainty identifications were of ‘the suspect’. A group of subjects also saw a set of photographs prior to the parade. The findings suggest that, When the man previously seen was not included, subjects were more likely to make a false positive identification on photographs than on a parade. In addition, subjects who had seen the photographs Wade a significantly greater proportion of false positive identifications on the subsequent parade.

scholarly journals Managing Risks Associated with Establishing the Metabolome of Dietary Phytochemicals (P06-010-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Colin Kay ◽  
Jessica Everhart ◽  
Atul Rathore
Keyword(s):  
Gas Phase ◽  
False Positive ◽  
Method Development ◽  
Ion Trap ◽  
Reference Standards ◽  
Molecular Rearrangement ◽  
Positive Identification ◽  
Hydrogen Elimination ◽  
False Positive Identification ◽  
Dietary Phytochemicals

Abstract Objectives Establishing the metabolome of dietary phytochemicals is complicated by the influence of the microbiome. Due to large numbers of human, microbial and hybrid human-microbial metabolites, false-positive identification via mass spectrometry (MS) is probable. Users must be aware of the influence of matrix and instrumental background environment upon the mass spectrum, which produce spectral features arising from fragmentation, gas-phase artifacts, molecular rearrangement, quasi-molecular ion or radical formation. Hydroxylated cyclic and polycyclic structures such as polyphenols are prone to multiple gas-phase artifacts, including water elimination (loss −17), hydrogen elimination (−1), radical fragmentation (loss −15, −14), Retro-Diels-Alder reactions (C-ring electron rearrangement; + or −2), or combinations thereof. In-source fragmentation is often observed for phase II conjugates, such as sulfate, glucuronide and glycine. Finally, polyphenol metabolites such as valerolactones, benzoic, phenylpropanoic and phenylacetic acids, are also products of MS fragmentation. As there are few reference standards available for confirmation or optimization, false-positive identification is likely. The objective of the present study was to highlight limitations with MS to ensure researchers make appropriate assumptions from their spectral data. Methods A quantitative metabolomics database comprising optimized spectral signals for fragmentation profiling of over 400 poly/phenols and metabolites was established using a UHPLC-coupled electrospray triple quadrupole-linear ion trap mass spectrometer (SCIEX QTRAP 6500+). Methods were established and utilized to interrogate over 3000 biospecimens derived from studies feeding various polyphenol-rich diets. Results Scanning for numerous metabolites reported in the literature using single transition monitoring, in both neat and extracted human and animal tissue matrices consistently identify peaks which were either artifacts, isomers, fragments or background noise, as confirmed relative to authentic reference standards. Conclusions Without ample MS experience, method development, validation and data interrogation, falsely identified metabolites will continue to occur and undoubtedly hinder future discovery. Funding Sources NIFA-USDA Hatch 1011757.

scholarly journals Controlling for background genetic effects using polygenic scores improves the power of genome-wide association studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Declan Bennett ◽  
Donal O’Shea ◽  
John Ferguson ◽  
Derek Morris ◽  
Cathal Seoighe
Keyword(s):  
Complex Traits ◽  
Association Studies ◽  
Real Data ◽  
Genetic Effects ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genotype Data ◽  
Phenotype Prediction ◽  
Genome Wide ◽  
Polygenic Scores

AbstractOngoing increases in the size of human genotype and phenotype collections offer the promise of improved understanding of the genetics of complex diseases. In addition to the biological insights that can be gained from the nature of the variants that contribute to the genetic component of complex trait variability, these data bring forward the prospect of predicting complex traits and the risk of complex genetic diseases from genotype data. Here we show that advances in phenotype prediction can be applied to improve the power of genome-wide association studies. We demonstrate a simple and efficient method to model genetic background effects using polygenic scores derived from SNPs that are not on the same chromosome as the target SNP. Using simulated and real data we found that this can result in a substantial increase in the number of variants passing genome-wide significance thresholds. This increase in power to detect trait-associated variants also translates into an increase in the accuracy with which the resulting polygenic score predicts the phenotype from genotype data. Our results suggest that advances in methods for phenotype prediction can be exploited to improve the control of background genetic effects, leading to more accurate GWAS results and further improvements in phenotype prediction.

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