Detecting fitness epistasis in recent admixed populations with genome-wide data

Abstract Background: Fitness epistasis, the interaction effect of genes at different loci on fitness, has an important contribution for adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is less detectable and remains poorly understood in human populations owing to the limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to strong confounding effect in a recently admixed population. Results: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value<8.11×10 -7 ) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pair of epistatic regions. We observed multiple pairs of co-expressed genes between the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in GTEx. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment. Conclusions: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to better understand adaptive evolution.

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Detecting fitness epistasis in recent admixed populations with genome-wide data

10.21203/rs.3.rs-20051/v1 ◽

2020 ◽

Author(s):

Xumin Ni ◽

Mengshi Zhou ◽

Heming Wang ◽

Karen He ◽

Uli Broeckel ◽

...

Keyword(s):

African Americans ◽

Adaptive Evolution ◽

Statistical Power ◽

Model Organisms ◽

P Value ◽

Human Populations ◽

Novel Approach ◽

Genome Wide Data ◽

Almost All ◽

Genomic Regions

Abstract Background: Fitness epistasis, the interaction effect of genes at different loci on fitness, has an important contribution for adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is less detectable and remains poorly understood in human populations owing to the limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to strong confounding effect in a recently admixed population. Results: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value<8.11×10-7) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pair of epistatic regions. We observed multiple pairs of co-expressed genes between the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in GTEx. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment. Conclusions: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to better understand adaptive evolution.

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Detecting fitness epistasis in recent admixed populations with genome-wide data

10.21203/rs.3.rs-20051/v2 ◽

2020 ◽

Author(s):

Xumin Ni ◽

Mengshi Zhou ◽

Heming Wang ◽

Karen He ◽

Uli Broeckel ◽

...

Keyword(s):

African Americans ◽

Adaptive Evolution ◽

Statistical Power ◽

Tissue Expression ◽

Model Organisms ◽

P Value ◽

Human Populations ◽

Novel Approach ◽

Genome Wide Data ◽

Almost All

Abstract Background: Fitness epistasis, the interaction effect of genes at different loci on fitness, has an important contribution for adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is less detectable and remains poorly understood in human populations owing to the limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to strong confounding effect in a recently admixed population.Results: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value<8.11×10-7) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pair of epistatic regions. We observed multiple pairs of co-expressed genes between the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in The Genotype-Tissue Expression (GTEx) data. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment.Conclusions: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to better understand adaptive evolution.

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A multi-ethnic polygenic risk score is associated with hypertension prevalence and progression throughout adulthood

10.1101/2021.10.31.21265717 ◽

2021 ◽

Author(s):

Nuzulul Kurniansyah ◽

Matthew O Goodman ◽

Tanika Kelly ◽

Tali Elfassi ◽

Kerri Wiggins ◽

...

Keyword(s):

African Americans ◽

Clinical Outcomes ◽

Risk Scores ◽

Training Dataset ◽

P Value ◽

Polygenic Risk Score ◽

Polygenic Risk ◽

Incident Hypertension ◽

Novel Approach ◽

Increased Risk

Background: We used summary statistics from previously-published GWAS of systolic and diastolic BP and of hypertension to construct Polygenic Risk Scores (PRS) to predict hypertension across diverse populations. Methods: We used 10,314 participants of diverse ancestry from BioMe to train trait-specific PRS. We implemented a novel approach to select one of multiple potential PRS based on the same GWAS, by optimizing the coefficient of variation across estimated PRS effect sizes in independent subsets of the training dataset. We combined the 3 selected trait-specific PRS as their unweighted sum, called "PRSsum". We evaluated PRS associations in an independent dataset of 39,035 individuals from eight cohort studies, to select the final, multi-ethnic, HTN-PRS. We estimated its association with prevalent and incident hypertension 4-6 years later. We studied hypertension development within HTN-PRS strata in a longitudinal, six-visit, longitudinal dataset of 3,087 self-identified Black and White participants from the CARDIA study. Finally, we evaluated the HTN-PRS association with clinical outcomes in 40,201 individuals from the MGB Biobank. Results: Compared to other race/ethnic backgrounds, African-Americans had higher average values of the HTN-PRS. The HTN-PRS was associated with prevalent hypertension (OR=2.10, 95% CI [1.99, 2.21], per one standard deviation (SD) of the PRS) across all participants, and in each race/ethnic background, with heterogeneity by background (p-value < 1.0x10-4). The lowest estimated effect size was in African Americans (OR=1.53, 95% CI [1.38, 1.69]). The HTN-PRS was associated with new onset hypertension among individuals with normal (respectively, elevated) BP at baseline: OR=1.71, 95% CI [1.55, 1.91] (OR=1.48, 95% CI [1.27, 1.71]). Association was further observed in age-stratified analysis. In CARDIA, Black participants with high HTN-PRS percentiles developed hypertension earlier than White participants with high HTN-PRS percentiles. The HTN-PRS was significantly associated with increased risk of coronary artery disease (OR=1.12), ischemic stroke (OR=1.15), type 2 diabetes (OR=1.19), and chronic kidney disease (OR=1.12), in the MGB Biobank. Conclusions: The multi-ethnic HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up across adulthood and is associated with clinical outcomes.

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Comparison of single genome and allele frequency data reveals discordant demographic histories

10.1101/182899 ◽

2017 ◽

Author(s):

Annabel C. Beichman ◽

Tanya N. Phung ◽

Kirk E. Lohmueller

Keyword(s):

Statistical Power ◽

Empirical Test ◽

Demographic History ◽

Empirical Studies ◽

Simulated Data ◽

Wide Distribution ◽

Model Organisms ◽

Human Populations ◽

Whole Genome ◽

Demographic Models

ABSTRACTInference of demographic history from genetic data is a primary goal of population genetics of model and non-model organisms. Whole genome-based approaches such as the Pairwise/Multiple Sequentially Markovian Coalescent (PSMC/MSMC) methods use genomic data from one to four individuals to infer the demographic history of an entire population, while site frequency spectrum (SFS)-based methods use the distribution of allele frequencies in a sample to reconstruct the same historical events. Although both methods are extensively used in empirical studies and perform well on data simulated under simple models, there have been only limited comparisons of them in more complex and realistic settings. Here we use published demographic models based on data from three human populations (Yoruba (YRI), descendants of northwest-Europeans (CEU), and Han Chinese (CHB)) as an empirical test case to study the behavior of both inference procedures. We find that several of the demographic histories inferred by the whole genome-based methods do not predict the genome-wide distribution of heterozygosity nor do they predict the empirical SFS. However, using simulated data, we also find that the whole genome methods can reconstruct the complex demographic models inferred by SFS-based methods, suggesting that the discordant patterns of genetic variation are not attributable to a lack of statistical power, but may reflect unmodeled complexities in the underlying demography. More generally, our findings indicate that demographic inference from a small number of genomes, routine in genomic studies of nonmodel organisms, should be interpreted cautiously, as these models cannot recapitulate other summaries of the data.

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Relationship of Workload and Double Role With Work Fatigue on Batik Craftsmen

Jurnal Endurance ◽

10.22216/jen.v4i2.4013 ◽

2019 ◽

Vol 4 (2) ◽

pp. 293

Author(s):

Herdianti Herdianti ◽

Tatik Maryana

Keyword(s):

Data Analysis ◽

Quantitative Research ◽

Sampling Technique ◽

Work Load ◽

Dual Role ◽

P Value ◽

Chi Square ◽

Cross Sectional ◽

Chi Square Test ◽

Almost All

Background: In Batik Mawar, almost all work is done manually using the hands and upper arms on a continuous basis combined with the rigor of work and the use of traditional tools. The work has a heavy workload because all the work process is done by the same craftsman causing fatigue besides that the worker also have double role. The purpose of this study is to determine the relationship between workload and dual role with feelings of fatigue on craftsmen batik roses.Method: This research is Quantitative research with Cross Sectional research design. The population in this study are all artisans in Batik Mawar. Sampling in this study using total sampling technique with the number of research samples as many as 40 respondents. Data analysis used by Univariat and Bivariat.Result: Result of data analysis using Chi-Square test for work load got value p-Value = 0,001. The result of data analysis using Chi-square test for double role got p-value = 0,031. Thus it is concluded that there is a meaningful relationship between workload and dual role with feeling tired. We recommend that craftsmen wash clothes 2 times a day, cook ready meals, other than together in completing the work at home Di Batik Mawar, hampir semua pekerjaan dikerjakan secara manual menggunakan tangan dan lengan atas secara berkesinambungan yang dikombinasi dengan ketelitian kerja dan penggunaan alat-alat tradisional. Pekerjaan mempunyai beban kerja yang berat dikarenakan semua proses kerja dilakukan oleh pengrajin yang sama sehingga menimbulkan kelelahan disamping itu pekerjanya juga memiliki peran ganda. Tujuan penelitian ini adalah untuk mengetahui hubungan beban kerja dan peran ganda dengan perasaan lelah pada pengrajin batik mawar.Metode: Penelitian ini merupakan penelitian Kuantitatif dengan desain penelitian Cross Sectional. Populasi dalam penelitian ini adalah semua pengrajin di Batik Mawar. Pengambilan sampel pada penelitian ini menggunakan teknik total sampling dengan jumlah sampel penelitian sebanyak 40 responden. Analisis data yang digunakan Univariat dan Bivariat.Hasil: Hasil analisis data yang menggunakan uji Chi-Square untuk beban kerja didapatkan nilai p-Value = 0,001. Hasil analisis data yang menggunakan uji Chi-square untuk peran ganda didapatkan nilai p-value= 0,031. Dengan demikian disimpulkan bahwa ada hubungan yang bermakna antara beban kerja dan peran ganda dengan perasaan lelah.Sebaiknya pengrajin mencuci pakaian 2 kali sehari, memasak makanan siap saji, selain itu dengan cara bersama-sama dalam menyelesaikan pekerjaan dirumah.

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An Emulation of Randomized Trials of Administrating Antipsychotics in PTSD Patients for Outcomes of Suicide-Related Events

Journal of Personalized Medicine ◽

10.3390/jpm11030178 ◽

2021 ◽

Vol 11 (3) ◽

pp. 178

Author(s):

Noah R. Delapaz ◽

William K. Hor ◽

Michael Gilbert ◽

Andrew D. La ◽

Feiran Liang ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Previous History ◽

Current Treatment ◽

Careful Consideration ◽

P Value ◽

Post Traumatic Stress ◽

Increased Risk ◽

History Of ◽

Almost All

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p < 0.0001 and false discovery rate-adjusted p value < 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed.

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A NOTE ON PHASING LONG GENOMIC REGIONS USING LOCAL HAPLOTYPE PREDICTIONS

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720006002272 ◽

2006 ◽

Vol 04 (03) ◽

pp. 639-647 ◽

Cited By ~ 6

Author(s):

ELEAZAR ESKIN ◽

RODED SHARAN ◽

ERAN HALPERIN

Keyword(s):

Large Scale ◽

Computational Cost ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Novel Approach ◽

Maximum Likelihood Criterion ◽

The Common ◽

Genomic Regions ◽

High Computational Cost ◽

Combining Information

The common approaches for haplotype inference from genotype data are targeted toward phasing short genomic regions. Longer regions are often tackled in a heuristic manner, due to the high computational cost. Here, we describe a novel approach for phasing genotypes over long regions, which is based on combining information from local predictions on short, overlapping regions. The phasing is done in a way, which maximizes a natural maximum likelihood criterion. Among other things, this criterion takes into account the physical length between neighboring single nucleotide polymorphisms. The approach is very efficient and is applied to several large scale datasets and is shown to be successful in two recent benchmarking studies (Zaitlen et al., in press; Marchini et al., in preparation). Our method is publicly available via a webserver at .

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Novel approach to enhance coastal habitat and biotope mapping with drone aerial imagery analysis

Scientific Reports ◽

10.1038/s41598-020-80612-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

João Gama Monteiro ◽

Jesús L. Jiménez ◽

Francesca Gizzi ◽

Petr Přikryl ◽

Jonathan S. Lefcheck ◽

...

Keyword(s):

Anthropogenic Impacts ◽

Spatial Scales ◽

Low Cost ◽

Human Populations ◽

Coastal Habitat ◽

Coastal Monitoring ◽

Monitoring Programs ◽

Novel Approach ◽

Aerial Platforms ◽

Rocky Habitats

AbstractUnderstanding the complex factors and mechanisms driving the functioning of coastal ecosystems is vital towards assessing how organisms, ecosystems, and ultimately human populations will cope with the ecological consequences of natural and anthropogenic impacts. Towards this goal, coastal monitoring programs and studies must deliver information on a range of variables and factors, from taxonomic/functional diversity and spatial distribution of habitats, to anthropogenic stress indicators such as land use, fisheries use, and pollution. Effective monitoring programs must therefore integrate observations from different sources and spatial scales to provide a comprehensive view to managers. Here we explore integrating aerial surveys from a low-cost Remotely Piloted Aircraft System (RPAS) with concurrent underwater surveys to deliver a novel approach to coastal monitoring. We: (i) map depth and substrate of shallow rocky habitats, and; (ii) classify the major biotopes associated with these environmental axes; and (iii) combine data from i and ii to assess the likely distribution of common sessile organismal assemblages over the survey area. Finally, we propose a general workflow that can be adapted to different needs and aerial platforms, which can be used as blueprints for further integration of remote-sensing with in situ surveys to produce spatially-explicit biotope maps.

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Transfer RNA genes experience exceptionally elevated mutation rates

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1801240115 ◽

2018 ◽

Vol 115 (36) ◽

pp. 8996-9001 ◽

Cited By ~ 12

Author(s):

Bryan P. Thornlow ◽

Josh Hough ◽

Jacquelyn M. Roger ◽

Henry Gong ◽

Todd M. Lowe ◽

...

Keyword(s):

Mutation Rate ◽

Trna Gene ◽

Gene Evolution ◽

Purifying Selection ◽

Mutation Rates ◽

Model Organisms ◽

Biological Synthesis ◽

Human Populations ◽

Trna Genes ◽

Simple Method

Transfer RNAs (tRNAs) are a central component for the biological synthesis of proteins, and they are among the most highly conserved and frequently transcribed genes in all living things. Despite their clear significance for fundamental cellular processes, the forces governing tRNA evolution are poorly understood. We present evidence that transcription-associated mutagenesis and strong purifying selection are key determinants of patterns of sequence variation within and surrounding tRNA genes in humans and diverse model organisms. Remarkably, the mutation rate at broadly expressed cytosolic tRNA loci is likely between 7 and 10 times greater than the nuclear genome average. Furthermore, evolutionary analyses provide strong evidence that tRNA genes, but not their flanking sequences, experience strong purifying selection acting against this elevated mutation rate. We also find a strong correlation between tRNA expression levels and the mutation rates in their immediate flanking regions, suggesting a simple method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution and indicates that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations.

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Hubungan Frekuensi Hemodialisis dengan Tingkat Stres pada Pasien Gagal Ginjal Kronik yang Menjalani Hemodialisis

Jurnal Keperawatan Silampari ◽

10.31539/jks.v1i2.7 ◽

2018 ◽

Vol 1 (2) ◽

pp. 139-153

Author(s):

Fitri Rahayu ◽

Topan Fernandoz ◽

Rafika Ramlis

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Study Design ◽

Significant Relationship ◽

P Value ◽

Analytic Method ◽

Stress Levels ◽

Almost All ◽

Moderate Stress

The aim of this study was to determine whether there is a relationship between hemodialysis frequency stress levels in patients with chronic renal failure undergoing hemodialysis at hemodialysis installation of dr. M. Yunus hospital Bengkulu City 2016. The study design used was a descriptive analytic method to explain each variable studied. The results showed that there was a significant relationship between the frequency of hemodialysis with the level of stress in patients with chronic renal failure, almost all respondents often undergo hemodialysis in hemodialysis installation in dr. M.Yunus hospital in Bengkulu city, of a total of 67 respondents almost half of respondents suffered moderate stress levels and no significant association between HD frequency with the stress levels of patients with CKD in Haemodialysis installation with p value 0.041 smaller than 0.05. The results of this study are expected to add insight and knowledge about the disease of CKD, and and is expected to continue this research in the context of a deeper and broader variables. Keywords: Frequency, Hemodialysis, Stress Levels.

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