Epidemiology of asthma and associated factors in an urban Pakistani population: adult asthma study-Karachi

Background

This study was conducted in order to determine the prevalence of asthma and associated risk factors in the adult population of Karachi, Pakistan.

Methods

This multi-stage, cross-sectional survey was conducted from May 2014–August 2015; comprising 1629 adults in 75 randomly selected clusters in Karachi, Pakistan. Definitions included: ‘self-reported asthma’, ‘reversibility in FEV₁^’ and ‘respiratory symptoms and reversibility in FEV₁’.

Results

Prevalence of asthma was 1.8% (self-reported) (95% CI: 1.0–2.6), 11.3% (reversibility in FEV₁) (95% CI: 9.4–13.3) and 6.6% (symptoms and reversibility in FEV₁) (95% CI: 5.1–8.1). Asthmatics were more likely to belong to the age group ≥38?years according to ‘reversibility in FEV₁’ and ‘respiratory symptoms and reversibility in FEV₁’ (AOR: 1.9, 95% CI: 1.2–3.3) and (AOR: 2.1, 95% CI: 1.1–4.2), respectively. Asthmatics were more likely to report history of allergies (AOR: 1.9, 95% CI: 1.2–2.9) and (AOR: 2.8, 95% CI: 1.7–4.8); and were exposed to environmental tobacco smoke (AOR: 1.6, 95% CI: 1.1–2.5) and (AOR: 1.9, 95% CI: 1.1–3.3) according to ‘reversibility in FEV₁’ and ‘respiratory symptoms and reversibility in FEV₁’, respectively. Asthmatics were more likely to report pack years of smoking ≥5 (AOR: 2.3, 95% CI: 1.1–4.7) according to ‘respiratory symptoms and reversibility in FEV₁’.

Conclusion

This study reports a high prevalence of asthma among Pakistani adults and calls for developing appropriate public health policies for prevention and control of asthma in the country. Further studies should be conducted to determine the national prevalence as well as follow-up studies to identify preventable causes for adult asthma.

     

Prediction of breed composition in an admixed cattle population

Swiss Fleckvieh was established in 1970 as a composite of Simmental (SI) and Red Holstein Friesian (RHF) cattle. Breed composition is currently reported based on pedigree information. Information on a large number of molecular markers potentially provides more accurate information. For the analysis, we used Illumina BovineSNP50 Genotyping Beadchip data for 90 pure SI, 100 pure RHF and 305 admixed bulls. The scope of the study was to compare the performance of hidden Markov models, as implemented in structure software, with methods conventionally used in genomic selection [BayesB, partial least squares regression (PLSR), least absolute shrinkage and selection operator (LASSO) variable selection)] for predicting breed composition. We checked the performance of algorithms for a set of 40 492 single nucleotide polymorphisms (SNPs), subsets of evenly distributed SNPs and subsets with different allele frequencies in the pure populations, using F_ST as an indicator. Key results are correlations of admixture levels estimated with the various algorithms with admixture based on pedigree information. For the full set, PLSR, BayesB and structure performed in a very similar manner (correlations of 0.97), whereas the correlation of LASSO and pedigree admixture was lower (0.93). With decreasing number of SNPs, correlations decreased substantially only for 5% or 1% of all SNPs. With SNPs chosen according to F_ST, results were similar to results obtained with the full set. Only when using 96 and 48 SNPs with the highest F_ST, correlations dropped to 0.92 and 0.90 respectively. Reducing the number of pure animals in training sets to 50, 20 and 10 each did not cause a drop in the correlation with pedigree admixture.     

Mapping of disease-associated variants in admixed populations

Recent developments in high-throughput genotyping and whole-genome sequencing will enhance the identification of disease loci in admixed populations. We discuss how a more refined estimation of ancestry benefits both admixture mapping and association mapping, making disease loci identification in admixed populations more powerful.     

Genetic variants on 17q21 are associated with asthma in a Han Chinese population

A genome-wide study has shown an association between SNPs located on 17q21 and asthma. Such associations have been identified in several populations, but little is known about the Han Chinese population. We conducted a case-control study in a Han Chinese population to investigate the relationship between SNPs located on 17q21 and asthma; 241 asthmatic patients and 212 healthy controls were recruited from the outpatient clinics of the Nanfang Hospital, Guangdong Province, southern China. We genotyped six SNPs (rs8067378, rs8069176, rs2305480, rs4795400, rs12603332, and rs11650680) located on 17q21 with the Sequenom MassARRAY iPLEX platform. For two of these six loci (rs2305480 and rs8067378), there was evidence of association with asthma, and there was a weak association of asthma with rs8069176. We confirm that genetic variants on 17q21 are associated with asthma in the Han Chinese population.     

Polymorphisms in the interleukin-4 receptor alpha chain: association with traits of allergy and asthma in an admixed population in Hawaii.

Single nucleotide polymorphisms (SNPs) in the gene encoding the interleukin-4 receptor alpha chain (IL-4R alpha) have been associated with IgE levels or clinical atopy in some populations. Two SNPs that encode S503P and Q576R in the intracytoplasmic domain of the receptor are associated with loss or gain of function, respectively. We investigated the frequency of these SNPs and their association with traits of allergic asthma in 36 unrelated subjects selected from a racially admixed, clinically ascertained study population with family histories of asthma. The frequency of the 1682 T to C substitution that encodes S503P was 0.11 (70 alleles analyzed, from 29 TT homozygotes and 6 TC heterozygotes). The frequency of the 1902 A to G substitution that encodes Q576R was 0.26 (68 alleles analyzed, from 20 AA homozygotes, 10 AG heterozygotes and 4 GG homozygotes). In this atopic admixed sample, no significant association was detected between the variant genotypes and serum IgE levels, percentage of eosinophils, skin test reactivity, diagnosis of asthma or methacholine reactivity. More conclusive findings await clinical characterization of non-atopic, non-asthmatic subjects as well as more efficient and extensive haplotyping.     

Outcrossing rates in an experimentally admixed population of self-compatible and self-incompatible Arabidopsis lyrata

The transition to self-compatibility from self-incompatibility is often associated with high rates of self-fertilization, which can restrict gene flow among populations and cause reproductive isolation of self-compatible (SC) lineages. Secondary contact between SC and self-incompatible (SI) lineages might re-establish gene flow if SC lineages remain capable of outcrossing. By contrast, intrinsic features of SC plants that reinforce high rates of self-fertilization could maintain evolutionary divergence between lineages. Arabidopsis lyrata subsp. lyrata is characterized by multiple origins of self-compatibility and high rates of self-fertilization in SC-dominated populations. It is unclear whether these high rates of selfing by SC plants have intrinsic or extrinsic causes. We estimated outcrossing rates and examined patterns of pollinator movement for 38 SC and 40 SI maternal parents sampled from an admixed array of 1509 plants sourced from six SC and six SI populations grown under uniform density. Although plants from SI populations had higher outcrossing rates (mean t_m = 0.78 ± 0.05 SE) than plants from SC populations (mean t_m = 0.56 ± 0.06 SE), outcrossing rates among SC plants were substantially higher than previous estimates from natural populations. Patterns of pollinator movement appeared to contribute to lower outcrossing rates for SC plants; we estimated that 40% of floral visits were geitonogamous (between flowers of the same plant). The relatively high rates of outcrossing for SC plants under standardized conditions indicate that selfing rates in natural SC populations of A. lyrata are facultative and driven by extrinsic features of A. lyrata, including patterns of pollinator movement.Subject terms: Plant evolution, Self incompatability, Ecological genetics, Population genetics     

Genetic diversity and population structure in urban white-tailed deer

Habitat fragmentation in urban areas has left many species isolated and vulnerable to loss of genetic variation. White-tailed deer (Odocoileus virginianus), however, thrive in urban areas. We compared genetic diversity and structure among deer in 2 urban metroparks with deer in a fenced reserve and with deer from an open, continuously distributed population to inform urban deer management. If urban deer maintain species' typical matrilineal genetic structure, removal of female groups may effectively reduce local abundance. However, if gene flow in urban areas is high, dispersal may impede efforts to reduce abundance. Although genetic diversity was high and mean relatedness was near zero in all locations, distributions of pairwise relatedness in urban metroparks and the fenced reserve contained greater proportions of closely and distantly related deer than the open locations, likely attributable to matrilineal structure. In addition, deer from the metroparks (approx. 65 km apart) were moderately differentiated (F_st = 0.092) indicating gene flow in urban areas may be less than in other landscapes. Our results indicate that removal of matrilineal groups may reduce local urban deer abundance without inducing immigration from surrounding areas. © The Wildlife Society, 2012     

Genetic variants of factor B in a population of Jordan

BF phenotyping was performed in a population of Jordan. The observed allele frequencies were as follows: BF*S = 0.5457, BF*F = 0.3744, BF*SO7 = 0.0763, BF*F1 = 0.0075. These values are in agreement with the geographic position and the ethnic composition of Jordan.     

Genetic variants influencing lipid levels and risk of dyslipidemia in Chinese population

Recently, several human genetic and genomewide association studies (GWAS) have discovered many genetic loci that are associated with the concentration of the blood lipids. To confirm the reported loci in Chinese population, we conducted a cross-section study to analyse the association of 25 reported SNPs, genotyped by the ABI SNaPshot method, with the blood levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in 1900 individuals by multivariate analysis. Logistic regression was applied to assess the association of the genetic loci with the risk of different types of dyslipidemia. Our study has convincingly identified that 12 of 25 studied SNPs were strongly associated with one or more blood lipid parameters (TC, LDL, HDL and TG). Among the 12 associated SNPs, 10 significantly influence the risk of one or more types of dyslipidemia. We firstly found four SNPs (rs12654264 in HMGCR; rs2479409 in PCSK9; rs16996148 in CILP2, PBX4; rs4420638 in APOE-C1-C4-C2) robustly and independently associate with four types of dyslipidemia (MHL, mixed hyperlipidemia; IHTC, isolated hypercholesterolemia; ILH, isolated low HDL-C; IHTG, isolated hypertriglyceridemia). Our results suggest that genetic susceptibility is different on the same candidate locus for the different populations. Meanwhile, most of the reported genetic variants strongly influence one or more plasma lipid levels and the risk of dyslipidemia in Chinese population.     

TagSNP transferability and relative loss of variability prediction from HapMap to an admixed population

Background

The application of a subset of single nucleotide polymorphisms, the tagSNPs, can be useful in capturing untyped SNPs information in a genomic region. TagSNP transferability from the HapMap dataset to admixed populations is of uncertain value due population structure, admixture, drift and recombination effects. In this work an empirical dataset from a Brazilian admixed sample was evaluated against the HapMap population to measure tagSNP transferability and the relative loss of variability prediction.

Methods

The transferability study was carried out using SNPs dispersed over four genomic regions: the PTPN22, HMGCR, VDR and CETP genes. Variability coverage and the prediction accuracy for tagSNPs in the selected genomic regions of HapMap phase II were computed using a prediction accuracy algorithm. Transferability of tagSNPs and relative loss of prediction were evaluated according to the difference between the Brazilian sample and the pooled and single HapMap population estimates.

Results

Each population presented different levels of prediction per gene. On average, the Brazilian (BRA) sample displayed a lower power of prediction when compared to HapMap and the pooled sample. There was a relative loss of prediction for BRA when using single HapMap populations, but a pooled HapMap dataset generated minor loss of variability prediction and lower standard deviations, except at the VDR locus at which loss was minor using CEU tagSNPs.

Conclusion

Studies that involve tagSNP selection for an admixed population should not be generally correlated with any specific HapMap population and can be better represented with a pooled dataset in most cases.     

Restricted gene flow between resident Oncorhynchus mykiss and an admixed population of anadromous steelhead

The species Oncorhynchus mykiss is characterized by a complex life history that presents a significant challenge for population monitoring and conservation management. Many factors contribute to genetic variation in O. mykiss populations, including sympatry among migratory phenotypes, habitat heterogeneity, hatchery introgression, and immigration (stray) rates. The relative influences of these and other factors are contingent on characteristics of the local environment. The Rock Creek subbasin in the middle Columbia River has no history of hatchery supplementation and no dams or artificial barriers. Limited intervention and minimal management have led to a dearth of information regarding the genetic distinctiveness of the extant O. mykiss population in Rock Creek and its tributaries. We used 192 SNP markers and collections sampled over a 5‐year period to evaluate the temporal and spatial genetic structures of O. mykiss between upper and lower watersheds of the Rock Creek subbasin. We investigated potential limits to gene flow within the lower watershed where the stream is fragmented by seasonally dry stretches of streambed, and between upper and lower watershed regions. We found minor genetic differentiation within the lower watershed occupied by anadromous steelhead (F_ST = 0.004), and evidence that immigrant influences were prevalent and ubiquitous. Populations in the upper watershed above partial natural barriers were highly distinct (F_ST = 0.093) and minimally impacted by apparent introgression. Genetic structure between watersheds paralleled differences in local demographics (e.g., variation in size), migratory restrictions, and habitat discontinuity. The evidence of restricted gene flow between putative remnant resident populations in the upper watershed and the admixed anadromous population in the lower watershed has implications for local steelhead productivity and regional conservation.     

Haplotype diversity of 17 Y-str loci in an admixed population from the Brazilian Amazon

The allelic and haplotype frequencies of 17 Y-STR loci most commonly used in forensic testing were estimated in a sample of 138 unrelated healthy males from Macapá, in the northern Amazon region of Brazil. The average gene diversity was 0.6554 ± 0.3315. 134 haplotypes of the 17 loci were observed, 130 of them unique and four present in two individuals each. The haplotype diversity index was 0.9996 + 0.0009, with the most frequent haplogroups being R1b (52.2%), E1b1b (11.6%), J2 (10.1%) and Q (7.2%). Most haplogroups of this population belonged to European male lineages (89.2%), followed by Amerindian (7.2%) and African (3.6%) lineages.     

Genetic variants associated with primary open angle glaucoma in Indian population

Glaucoma is a very common disorder of the eye wherein the disturbance of the structural or functional integrity of the optic nerve causes characteristic atrophic changes in the optic nerve, which may lead to specific visual field defects over time. Primary open angle glaucoma (POAG) is most frequent among the three principle glaucoma subtypes. With well-established role of genes like Myocilin (MYOC), Optineurin (OPTN) and WD repeat Domain 36, (WDR36), at least 29 genetic loci have been found till date to be linked to POAG. Moreover, association studies have found 66 loci with 76 genes associated to POAG till date with conflicting results. This particular study is to summarize the current knowledge regarding the change in glaucoma prevalence worldwide and in India from 1993 onwards and compiles all the studied genes that are involved in POAG pathogenesis in Indian population.     

Association of serum lipid components and obesity with genetic ancestry in an admixed population of elderly women

The prevalence of metabolic disorders varies among ethnic populations and these disorders represent a critical health care issue for elderly women. This study investigated the correlation between genetic ancestry and body composition, metabolic traits and clinical status in a sample of elderly women. Clinical, nutritional and anthropometric data were collected from 176 volunteers. Genetic ancestry was estimated using 23 ancestry-informative markers. Pearsons correlation test was used to examine the relationship between continuous variables and an independent samples t-test was used to compare the means of continuous traits within categorical variables. Overall ancestry was a combination of European (57.49%), Native American (25.78%) and African (16.73%). Significant correlations were found for European ancestry with body mass index (r = 0.165; p = 0.037) and obesity (mean difference (MD) = 5.3%; p = 0.042). African ancestry showed a significant correlation with LDL (r = 0.159, p = 0.035), VLDL (r = −0.185; p = 0.014), hypertriglyceridemia (MD = 6.4%; p = 0.003) and hyperlipidemia (MD = 4.8%; p = 0.026). Amerindian ancestry showed a significant correlation with triglyceride levels (r = 0.150; p = 0.047) and hypertriglyceridemia (MD = 4.5%; p = 0.039). These findings suggest that genetic admixture may influence the etiology of lipid metabolism-related diseases and obesity in elderly women.     

Population analysis of vitamin D receptor polymorphisms and the role of genetic ancestry in an admixed population

The vitamin D receptor (VDR) is an essential protein related to bone metabolism. Some VDR alleles are differentially distributed among ethnic populations and display variable patterns of linkage disequilibrium (LD). In this study, 200 unrelated Brazilians were genotyped using 21 VDR single nucleotide polymorphisms (SNPs) and 28 ancestry informative markers. The patterns of LD and haplotype distribution were compared among Brazilian and the HapMap populations of African (YRI), European (CEU) and Asian (JPT+CHB) origins. Conditional regression and haplotype-specific analysis were performed using estimates of individual genetic ancestry in Brazilians as a quantitative trait. Similar patterns of LD were observed in the 5' and 3' gene regions. However, the frequency distribution of haplotype blocks varied among populations. Conditional regression analysis identified haplotypes associated with European and Amerindian ancestry, but not with the proportion of African ancestry. Individual ancestry estimates were associated with VDR haplotypes. These findings reinforce the need to correct for population stratification when performing genetic association studies in admixed populations.     

Genetic variation in BDNF is associated with allergic asthma and allergic rhinitis in an ethnic Chinese population in Singapore

Allergic diseases affect more than 25% of the world population and result from a complex interplay between genetic and environmental factors. Recent evidence has shown that BDNF (Brain Derived Neurotrophic Factor) could serve as an important marker of allergic disease. Increased levels of BDNF in blood, bronchoalveolar lavage fluid and nasal lavage fluid positively correlate with disease activity and severity in patients with allergic rhinitis (AR), asthma and atopic eczema. However, reports on the association between genetic variation in BDNF and allergic disease have been controversial. This study therefore aims to clarify the relationship between single nucleotide polymorphisms (SNPs) in BDNF and a genetic predisposition to AR and asthma in an ethnic Chinese population of Singapore. Volunteers with a self-reported history of asthma (718 subjects) or a history of AR as determined by a researcher-administered questionnaire (795 subjects) were used in this study, alongside controls with no personal or family history of allergy (717 subjects). The association results identified a significant association for the tagSNP rs10767664 with a significant P_Dominant = 0.0007 and OR = 1.3 for AR and P_Dominant = 0.0005 and OR = 1.3 for asthma (using a dominant model of association). The haplotype based analysis also identified a significant association further confirming the single SNP association. The SNP rs10767664 is strongly linked (r² = 0.95) to the functional polymorphism rs6265 (Val66Met), which has previously been reported to be associated to allergic phenotypes and also shown to affect BDNF expression. BDNF is a therefore a key molecular player in allergy. Further studies on polymorphisms within BDNF may shed light on its role in the pathogenesis of allergic diseases and potentially serve as biomarkers for allergic disease.     

Genetic variants in epoxide hydrolases modify the risk of oligozoospermia and asthenospermia in Han-Chinese population

Objectives

Epoxide hydrolases are involved in detoxifying and excreting the environmental chemicals, which are associated with decreased semen quality and male infertility. We hypothesized that polymorphisms in epoxide hydrolases may be associated with risk of oligozoospermia and asthenospermia.

Design and methods

In this study, 468 fertile controls and 672 idiopathic male infertile patients were recruited. SNPstream and TaqMan assay were used to genotype four single nucleotide polymorphisms in EPHX1 and EPHX2. The semen analysis was performed by computer-assisted semen analysis system.

Results

Our results demonstrated that rs1042064 of EPHX2 was significantly associated with decreased risk of oligozoospermia (OR = 0.65, 95% CI: 0.44–0.98) and asthenospermia (OR = 0.66, 95% CI: 0.46–0.94).

Conclusions

Our results provided evidence that genetic variants in epoxide hydrolases may modify the risk of oligozoospermia and asthenospermia in Han-Chinese population.     

Genetic polymorphisms of pharmacogenomic VIP variants in the Kyrgyz population from northwest China

Pharmacogenomic variant information is well known for major human populations; however, this information is less commonly studied in minorities. In the present study, we genotyped 85 very important pharmacogenetic (VIP) variants (selected from the PharmGKB database) in the Kyrgyz population and compared our data with other four major human populations including Han Chinese in Beijing, China (CHB), the Japanese in Tokyo, Japan (JPT), a northern and western Europe population (CEU), and the Yoruba in Ibadan, Nigeria (YRI). There were 13, 12 and 16 of the selected VIP variant genotype frequencies in the Kyrgyz which differed from those of the CHB, JPT and CEU, respectively (p < 0.005). In the YRI, there were 32 different variants, compared to the Kyrgyz (p < 0.005). Genotype frequencies of ADH1B, AHR, CYP3A5, PTGS2, VDR, and VKORC1 in the Kyrgyz differed widely from those in the four populations. Haplotype analyses also showed differences among the Kyrgyz and the other four populations. Our results complement the information provided by the database of pharmacogenomics on Kyrgyz. We provide a theoretical basis for safer drug administration and individualized treatment plans for the Kyrgyz. We also provide a template for the study of pharmacogenomics in various ethnic minority groups in China.