scholarly journals Variation among human populations in endometriosis and PCOS: a test of the inverse comorbidity model

2021 ◽  
Author(s):  
Bernard Crespi
Keyword(s):  
Polycystic Ovary ◽  
African Ancestry ◽  
Serum Testosterone ◽  
Population Variation ◽  
Human Populations ◽  
Prenatal Testosterone ◽  
Asian Populations ◽  
Digit Ratios ◽  
African Populations ◽  
Show Evidence

ABSTRACT Evidence linking endometriosis to low prenatal testosterone, and evidence that risk of polycystic ovary syndrome (PCOS) is associated with high prenatal testosterone, has motivated the hypothesis that endometriosis and PCOS exhibit inverse comorbidity. The inverse comorbidity hypothesis predicts that populations exhibiting higher prevalence of one disorder should show lower prevalence of the other. To test this prediction, data were compiled from the literature on the prevalence of endometriosis and PCOS, levels of serum testosterone in women during pregnancy, and digit ratios as indicators of prenatal testosterone, in relation to variation in inferred or observed population ancestries. Published studies indicate that rates of endometriosis are highest in women from Asian populations, intermediate in women from European populations, and lowest in women from African populations (i.e., with inferred or observed African ancestry); by contrast, rates of PCOS show evidence of being lowest in Asian women, intermediate in Europeans, and highest in individuals from African populations. Women from African populations also show higher serum testosterone during pregnancy (which may increase PCOS risk, and decrease endometriosis risk, in daughters), and higher prenatal testosterone (as indicated by digit ratios), than European women. These results are subject to caveats involving ascertainment biases, socioeconomic, cultural and historical effects on diagnoses, data quality, uncertainties regarding the genetic and environmental bases of population differences, and population variation in the causes and symptoms of PCOS and endometriosis. Despite such reservations, the findings provide convergent, preliminary support for the inverse comorbidity model, and they should motivate further tests of its predictions.

scholarly journals pmTR database: population matched (PM) germline allelic variants of T-cell receptor (TR) loci

2020 ◽  
Author(s):  
Julian Dekker ◽  
Jacques J.M. van Dongen ◽  
Marcel J.T. Reinders ◽  
Indu Khatri
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Receptor ◽  
Genetic Basis ◽  
Cell Receptor ◽  
Human Populations ◽  
Allelic Variants ◽  
Asian Populations ◽  
African Populations ◽  
Source Of Information

AbstractT-cell receptor (TR) germline alleles are arranged, organized and made available to the research community by the IMGT database. This state-of-the-art database, however, does not provide information regarding population specificity and allelic frequencies of the genes all four human TR loci (TRA, TRB, TRG and TRD). The specificity of allelic variants to different human populations can, however, be a rich source of information when studying the genetic basis of population-specific immune responses in vaccination and disease. To make TR germline alleles available for such population-specific studies, we meticulously identified true germline alleles enriched with complete TR allele sequences and their frequencies across 26 different human populations, profiled by “1,000 Genomes data”. We identified 205 TRAV, 249 TRBV, 16 TRGV and 5 TRDV germline alleles supported by at least four haplotypes (= minimum of two individuals). The diversity of germline allelic variants in the TR loci is highest in Africans followed by Non-African populations. A majority of the Non-African alleles are specific to the Asian populations, suggesting a diverse profile of TR germline alleles in different human populations. Interestingly, the alleles known in the IMGT database are frequent and common across all the superpopulations. We believe that this new set of genuine germline TR sequences represents a valuable new resource which we have made available through the new population-matched TR (pmTR) database, accessible via https://pmtrig.lumc.nl/.

scholarly journals Genetic Predictors of Type 2 Diabetes in Yakuts

2021 ◽  
Vol 11 (3) ◽  
pp. 355-360
Author(s):  
Nadezhda I. Pavlova ◽  
Aleksandra T. Diakonova ◽  
Vladislav A. Alekseev ◽  
Lyubovy A. Sydykova ◽  
Nadezhda E. Maksimova ◽  
...  
Keyword(s):  
Low Frequency ◽  
Human Populations ◽  
Study Cohort ◽  
Asian Populations ◽  
Ethnic Populations ◽  
Genetic Predictors ◽  
African Populations ◽  
Polymorphic Variants ◽  
Tcf7l2 Rs7903146

The goal of this study was to investigate the distribution of alleles and genotypes of the KCNJ11 rs5219, PPARG rs1801282, TCF7L2 rs7903146/rs12255372 SNPs in Yakuts with T2D, in comparison with other ethnic populations. Methods and Results: The study cohort consisted of 26 Yakut patients diagnosed with T2D (YKT2D). Genotyping of rs5219 (KCNJ11), rs1801282 (PPARG), rs7903146 and rs12255372 (TCF7L2) SNPs was performed by pyrosequencing using PyroMark Q48 Autoprep sequencer (QIAGEN). The genotyping of the studied group of Yakuts did not reveal statistically significant differences between control groups and YKT2D patients with respect to the polymorphic variants of the KCNJ11, PPARG, and TCF7L2 genes. The allele frequency analysis of the polymorphisms of the KCNJ11, PPARG, and TCF7L2 genes demonstrated a low frequency of the risk T-allele in the TCF7L2 (rs7903146, rs12255372) in Asian populations, compared to other human populations. We identified three haplotypes [CG (90.5%), TT (6.8%), and TG (2.7%)] in the YKT2D cohort. Also, we observed a strong LD between two SNPs (rs7903146 and rs12255372) of the TCF7L2 gene in the majority of groups, including YKT2D (D '= 1, LOD = 4.92), except for African populations, where a very weak LD (D '= 0.001-0.435, LOD = 0.0-0.73) was observed.

The frequency of late-onset 21-hydroxylase and 11 beta-hydroxylase deficiency in women with polycystic ovary syndrome

1997 ◽  
pp. 670-674 ◽  
Author(s):  
Y Sahin ◽  
F Kelestimur
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Late Onset ◽  
Polycystic Ovary ◽  
Serum Testosterone ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
Ovary Syndrome ◽  
Biochemical Features

OBJECTIVE: To determine the frequency of late-onset adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) and 11 beta-hydroxylase (11 beta-OH) deficiency in women with clinical and biochemical features of polycystic ovary syndrome (PCOS). DESIGN: Eighty-three consecutively selected women with PCOS and eighteen normal women were included in the study. METHODS: Ultrasound, clinical and hormonal parameters were used to define PCOS. Basal FSH, LH, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and cortisol levels were measured. Serum 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (11-DOC) levels were also measured before, 30 and 60 min after a single bolus injection of 0.25 mg ACTH (1-24) at 0900 h during the mid-follicular phase of the cycle. ACTH-stimulated 17-OHP levels > 30 nmol/l were considered as the criteria of 21-OH deficiency. The diagnosis 11 beta-OH deficiency was made if the adrenal 11-DOC response to ACTH stimulation exceeded threefold the 95th percentile of controls. RESULTS: Basal serum testosterone, free testosterone, androstenedione, DHEA-S, cortisol and 11-DOC levels were significantly higher in PCOS than in control subjects. ACTH-stimulated 17-OHP (P < 0.05) and 11-DOC (P < 0.0005) levels were found to be significantly higher in patients with PCOS than in controls. Seven (8.4%) patients had an 11-DOC response to ACTH higher than threefold the 95th percentile of controls, while no patients showed evidence of 21-OH deficiency. CONCLUSIONS: We have found that 8.4% of the women with clinical and biochemical features of PCOS could be presumed to have 11 beta-OH deficiency. No patients among the women with PCOS showed evidence of 21-OH deficiency. 11 beta-OH deficiency is unexpectedly more common than 21-OH deficiency in women with PCOS.

Application of the Optimized Summed Score Attributes Method for Sex Estimation

2021 ◽  
Author(s):  
Holly Long ◽  
Alexandra Klales
Keyword(s):  
Sexual Dimorphism ◽  
African Ancestry ◽  
European Ancestry ◽  
Sex Bias ◽  
Sex Estimation ◽  
Black African ◽  
Asian Populations ◽  
Novel Approach ◽  
Calibration Sample ◽  
Accuracy Rates

The optimized summed scored attributes (OSSA) method was first developed for cranial ancestry estimation (Hefner & Ousley 2014). Tallman and Go (2018) adapted this method for sex estimation with the five skull traits described by Buikstra and Ubelaker (1994) and Walker (2008). Using an Asian sample, Tallman and Go (2018) achieved moderate accuracy rates (83.7% calibration; 81.9% validation) but also high sex bias (29.1% calibration; 34.5% validation), possibly due to lower levels of sexual dimorphism in Asian populations. To further explore this novel approach to sex estimation, the OSSA method was applied to a U.S. Black/African ancestry and White/European ancestry calibration sample (N = 700). Accuracy rates were 77.4% in Black individuals and 77.2% in White individuals. Despite generally higher levels of sexual dimorphism in these groups, a high sex bias still occurred (15.4% Black individuals; –20.5% White individuals) using OSSA. The method was tested in a separate validation sample (N = 200) with accuracy of 78.0% in Black individuals (8.0% sex bias) and 70.0% in White individuals (–56.0% sex bias). When these same traits were tested with Walker’s (2008) logistic regression and in the MorphoPASSE Program (Klales 2018) using random forest modeling, accuracy rates varied ,with OSSA (77.3% correct), performing slightly better than Walker’s (2008) method (75.6% correct) but worse than MorphoPASSE (85.3% correct). The higher accuracy and lower sex bias in MorphoPASSE suggests that the Walker (2008) traits can be used to accurately estimate sex with statistical approaches more appropriate and robust than OSSA.

Population-specific genome graphs improve high-throughput sequencing data analysis: A case study on the Pan-African genome

2021 ◽  
Author(s):  
H. Serhat Tetikol ◽  
Kubra Narci ◽  
Deniz Turgut ◽  
Gungor Budak ◽  
Ozem Kalay ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Information Overload ◽  
African Ancestry ◽  
Sample Selection ◽  
Variant Calling ◽  
Population Diversity ◽  
Human Populations ◽  
Sequencing Data ◽  
Bioinformatics Pipeline ◽  
Graph Augmentation

ABSTRACTGraph-based genome reference representations have seen significant development, motivated by the inadequacy of the current human genome reference for capturing the diverse genetic information from different human populations and its inability to maintain the same level of accuracy for non-European ancestries. While there have been many efforts to develop computationally efficient graph-based bioinformatics toolkits, how to curate genomic variants and subsequently construct genome graphs remains an understudied problem that inevitably determines the effectiveness of the end-to-end bioinformatics pipeline. In this study, we discuss major obstacles encountered during graph construction and propose methods for sample selection based on population diversity, graph augmentation with structural variants and resolution of graph reference ambiguity caused by information overload. Moreover, we present the case for iteratively augmenting tailored genome graphs for targeted populations and test the proposed approach on the whole-genome samples of African ancestry. Our results show that, as more representative alternatives to linear or generic graph references, population-specific graphs can achieve significantly lower read mapping errors, increased variant calling sensitivity and provide the improvements of joint variant calling without the need of computationally intensive post-processing steps.

scholarly journals Correlation of serum androgen and gonadotropin with anti-mullerian hormone in polycystic ovarian syndrome in Eastern Indian population

2019 ◽  
Vol 8 (1) ◽  
pp. 256
Author(s):  
Somnath Singh Raghuvanshi ◽  
Anirban Sinha ◽  
Animesh Maiti ◽  
Partha Pratim Chakraborty ◽  
Asish Kumar Basu ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovarian Syndrome ◽  
Pulse Generator ◽  
Polycystic Ovary ◽  
Serum Testosterone ◽  
Pulse Frequency ◽  
Strong Positive Correlation ◽  
Ovary Syndrome ◽  
Cross Sectional ◽  
Ovarian Syndrome

Background: Ovarian steroidogenesis requires gonadotropin stimulation, Luteinizing Hormone (LH) is a key factor in the hyperandrogenaemia of the polycystic ovary syndrome. Progesterone is the primary regulator of Gonadotropin-Releasing Hormone (GnRH) pulse frequency; however, in the polycystic ovary syndrome, the GnRH pulse generator is relatively resistant to the negative feedback effects of progesterone.  Study aims to evaluate the association of Anti-mullerian hormone with serum androgen and gonadotropin level in adolescents and young women of Polycystic Ovary Syndrome (PCOS).Methods: This was a single centre observational Cross-sectional study carried out in the department of Endocrinology and metabolism, Medical College, Kolkata from March 2017 to January 2019. Total number of study subjects were 207 out of which 138 were cases.Results: The AMH had strong positive correlation with serum testosterone in both case and control groups (r 0.542, p<0.001 and r 0.57, p<0.001) respectively .After the adjustment of age and BMI , the AMH moderately positive  but extremely significant correlation with serum testosterone as compare to control.Conclusions: Hyperandrogenaemia and higher ratio of LH and FSH associated with higher serum AMH level is associated with the higher serum AMH in polycystic ovarian syndrome.

scholarly journals Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry

2019 ◽  
Vol 25 (10) ◽  
pp. 2455-2467 ◽  
Author(s):  
Tim B. Bigdeli ◽  
◽  
Giulio Genovese ◽  
Penelope Georgakopoulos ◽  
Jacquelyn L. Meyers ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Large Fraction ◽  
African Ancestry ◽  
Common Variant ◽  
Human Populations ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Common Genetic Variants

Abstract Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations.

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