Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “population stratification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed2005

Integrating genomics and transcriptomics with geo-ethnicity and the environment for the resolution of complex cardiovascular diseases.

One of the crucial steps on the way to individualized medicine to treat cardiovascular disease (CVD) is to better understand the identities, roles, extent and at least the major patterns of interaction between influential genomic and environmental factors. It is clear that such a bold goal can hardly be achieved without a major upgrade of our conceptualization of the phenomena studied, taking advantage of recent developments of novel technological and computational tools. Firstly, the search for the genomic components of the most common multifactorial CVDs is no longer restricted to protein-coding genes; truly genome-wide investigations should replace them in both humans and animal models. Secondly, the 'environment' has also undergone semantic expansion, incorporating such remote constituents as developmental plasticity and epigenetics on one side, and socioeconomic status on the other. To elucidate and analyze the resulting complex picture, appropriate statistical models and approaches need to be designed to tackle issues such as population stratification and admixture, multiple testing, and multidimensionality reduction in models involving multiple genes and environmental factors. Eventually, an integrated platform bringing together all of the above will probably be necessary to secure relevant information specific to a particular combination of conditions and settings (age, geo-ethnicity and exposure), which may perhaps become visible only after a step back, through systems (network) biology.

Animals↗
PubMed2006

[Introduction on "case-sibling control design"].

OBJECTIVE: To introduce the design and statistical methods of case-sibling control design and to analyze the published data. METHODS: Data from an association study between the coronary heart disease and methylenetetrahydrofolate reductase gene C677T polymorphism was analyzed by the sib transmission/disequibrium test (s-TDT) and the sibship disequilibrium (SDT) methods. RESULTS: Using s-TDT method, Z value was 0.27 with P > 0.05. The result of SDT method showed that chi-square was 0.31 with 1 df, P > 0.05. All results suggested that neither s-TDT nor SDT showed significant difference between the transmitted and untransmitted methylenetetrahydrofolate reductase gene C677T allele distributions. CONCLUSION: Case-sibling control design might avoid population stratification by using siblings as controls thus might be used to test association and linkage between genes and disease.

Case-Control Studies↗
PubMed1995

Association of attention-deficit disorder and the dopamine transporter gene.

Attention-deficit hyperactivity disorder (ADHD) has been shown to be familial and heritable, in previous studies. As with most psychiatric disorders, examination of pedigrees has not revealed a consistent Mendelian mode of transmission. The response of ADHD patients to medications that inhibit the dopamine transporter, including methylphenidate, amphetamine, pemoline, and bupropion, led us to consider the dopamine transporter as a primary candidate gene for ADHD. To avoid effects of population stratification and to avoid the problem of classification of relatives with other psychiatric disorders as affected or unaffected, we used the haplotype-based haplotype relative risk (HHRR) method to test for association between a VNTR polymorphism at the dopamine transporter locus (DAT1) and DSM-III-R-diagnosed ADHD (N = 49) and undifferentiated attention-deficit disorder (UADD) (N = 8) in trios composed of father, mother, and affected offspring. HHRR analysis revealed significant association between ADHD/UADD and the 480-bp DAT1 allele (chi 2 7.51, 1 df, P = .006). When cases of UADD were dropped from the analysis, similar results were found (Chi 2 7.29, 1 df, P = .007). If these findings are replicated, molecular analysis of the dopamine transporter gene may identify mutations that increase susceptibility to ADHD/UADD. Biochemical analysis of such mutations may lead to development of more effective therapeutic interventions.

Adolescent↗
PubMed1993

Genotype relative risks: methods for design and analysis of candidate-gene association studies.

Design and analysis methods are presented for studying the association of a candidate gene with a disease by using parental data in place of nonrelated controls. This alternative design eliminates spurious differences in allele frequencies between cases and nonrelated controls resulting from different ethnic origins and population stratification for these two groups. We present analysis methods which are based on two genetic relative risks: (1) the relative risk of disease for homozygotes with two copies of the candidate gene versus homozygotes without the candidate gene and (2) the relative risk for heterozygotes with one copy of the candidate gene versus homozygotes without the candidate gene. In addition to estimating the magnitude of these relative risks, likelihood methods allow specific hypotheses to be tested, namely, a test for overall association of the candidate gene with disease, as well as specific genetic hypotheses, such as dominant or recessive inheritance. Two likelihood methods are presented: (1) a likelihood method appropriate when Hardy-Weinberg equilibrium holds and (2) a likelihood method in which we condition on parental genotype data when Hardy-Weinberg equilibrium does not hold. The results for the relative efficiency of these two methods suggest that the conditional approach may at times be preferable, even when equilibrium holds. Sample-size and power calculations are presented for a multitiered design. The purpose of tier 1 is to detect the presence of an abnormal sequence for a postulated candidate gene among a small group of cases. The purpose of tier 2 is to test for association of the abnormal variant with disease, such as by the likelihood methods presented. The purpose of tier 3 is to confirm positive results from tier 2. Results indicate that required sample sizes are smaller when expression of disease is recessive, rather than dominant, and that, for recessive disease and large relative risks, necessary sample sizes may be feasible, even if only a small percentage of the disease can be attributed to the candidate gene.

Genetic Diseases, Inborn↗
PubMed1993

The haplotype-relative-risk (HRR) method for analysis of association in nuclear families.

One major problem in studying an association between a marker locus and a disease is the selection of an appropriate group of controls. However, this problem of population stratification can be circumvented in a quite elegant manner by family-based methods. The haplotype-relative-risk (HRR) method, which samples nuclear families with a single affected child and uses the parental haplotypes not transmitted to that child as a control individual, represents such a method for estimating the relative risk of a marker phenotype. In the special case of a recessive disease, it was already known that the equivalence of the HRR method with the classical relative risk (RR) obtained from independent samples holds only if the probability theta of a recombination between marker and disease locus is zero. We extend this result to an arbitrary mode of inheritance. Furthermore, we compare the distribution of the estimators for HRR and RR and show that, in the case of a positive linkage disequilibrium between a marker and disease allele, the distribution of the estimator for HRR is (stochastically) smaller than that for RR, irrespective of the recombination fraction. The practical implication of this result is that, for the HRR method, there is no tendency to give unduly high risk estimators, even for theta > 0. Finally, we give an expression for the standard error of the estimator for HRR by taking into account the nonindependence of transmitted and nontransmitted parental marker alleles in the case of theta > 0.

Alleles↗
PubMed1996

Frequency analysis of large CAG/CTG trinucleotide repeats in schizophrenia and bipolar affective disorder.

Much interest has recently been focussed on the possibility of the involvement of unstable DNA in the etiology of schizophrenia and bipolar affective disorder (BPAD), following several publications that report increases in frequency of large CAG/CTG repeats in affected individuals. Using the Repeat Expansion Detection (RED) technique, we have performed a matched control pair analysis for both disorders. No significant differences in CAG/CTG repeat sizes were observed for 52 bipolar affecteds and matched controls (P = 0.15), and borderline significance was observed for 54 schizophrenia affecteds and matched controls (P = 0.05), using a (CTG)10 oligonucleotide (one-tailed t-tests for paired samples). Furthermore, using a (CTG)17 oligonucleotide, no significant differences were observed for 58 bipolar affecteds and 55 schizophrenia affecteds compared to 81 unmatched controls. No significant sex effect was observed for either group, and no significant differences in repeat size were found for responders and non-responders to drug treatments. More importantly, there was no significant correlation (either positive or negative) between age of onset of disease and size of repeat. We thus cannot conclude that CAG/CTG trinucleotides are involved in psychotic disorders and that either the differences observed in similar studies may be the result of population stratification, or that the increased frequency of larger repeats amongst affected individuals is a much smaller effect than previously thought.

Adult↗
PubMed1998

Association of alcohol or other drug dependence with alleles of the mu opioid receptor gene (OPRM1).

Opioidergic neurotransmission and, specifically, the mu opioid receptor have been implicated in the reinforcing effects of a variety of drugs of abuse. Consequently, the present study examined the association of a polymorphic (CA)n repeat at the OPRM1 locus (the gene coding for the mu opioid receptor) to alcohol or drug dependence in 320 Caucasian and 108 African-American substance-dependent or control subjects. Among Caucasians, suggestion of a modest association, which could be interpreted as statistically significant (p = 0.03), was observed between OPRM1 alleles and substance (alcohol, cocaine, or opioid) dependence. Analysis by specific substance showed only a trend level association to alcohol dependence. Comparisons among African Americans yielded no evidence for association. Further studies of the association between alleles of the OPRM1 gene and substance dependence appear warranted, particularly if they use a family-based approach to control for population stratification. Phenotypes other than a broad diagnostic categorization, such as opioid antagonist effects on drinking behavior in alcoholics, may provide more consistent evidence of a role for OPRM1 in behavioral variability.

Adult↗
PubMed1989

Seasonality of birth in schizophrenia. An insufficient stratification of control population?

The seasonality of birth in 142 schizophrenics from Barcelona (Spain) has been studied, showing a pattern similar to that described by other authors, with a maximum in winter. If sample is compared with the local general population there are significant differences, but these disappear when the comparison is made with a control population properly stratified by age, sex, place of birth, place of residence and social status. The same results are obtained using statistical methods suggested by other authors. The seasonality pattern usually obtained in schizophrenia could be due to a selective stratification of the ill population based on variables that might or might not be related to illness.

Adolescent↗
PubMed1994

Mutation profiles of phenylketonuria in Quebec populations: evidence of stratification and novel mutations.

Independent phenylketonuria (PKU) chromosomes (n = 109) representing 80% of a proband cohort in Quebec province carry 18 different identified mutations in 20 different mutation/haplotype combinations. The study reported here, the third in a series on Quebec populations, was done in the Montreal region and predominantly on French Canadians. It has identified three novel mutations (A309D, D338Y, and 1054/1055delG[352fs]) and one unusual mutation/RFLP haplotype combination (E280K on Hp 2). The relative frequencies and distribution of PKU mutations were then compared in three regions and population subsets (eastern Quebec, French Canadian; western Quebec, French Canadian; and Montreal, non-French Canadian). The distributions of the prevalent and rare mutations are nonrandom and provide evidence for genetic stratification. The latter and the presence of eight unusual mutation/haplotype combinations in Quebec families with European ancestries (the aforementioned four and M1V, I65T, S349P, and R408W on Hp 1) corroborate demographic and anthropologic evidence, from elsewhere, for different origins of French Canadians in eastern and western Quebec.

DNA Mutational Analysis↗
PubMedDate not supplied

[The isolation of tick-borne encephalitis virus strains and the determination of the scope of immune stratification among the population and the domestic animals on the northern Russian plain].

Between 1986 and 1987 the authors conducted virological survey of 689 Ixodes persulcatus and 420 mouse-like and insectivorous rodents at the territory of Arkhangelsk Province and the Republic of Komi. A total of 8 strains of tick-borne encephalitis virus were isolated. Out of them 3 strains were isolated from small mammalians (2 from Clethrionomys glareolus, 1 from Microtus oeconomus) at the southeastern areas of Arkhangelsk Province within the middle taiga subarea, 5 strains were isolated from I. persulcatus (the rate of infection was 1.25 per cent) gathered in the southeastern Komi within the southern margins of the middle taiga subarea. PHAT investigation of the sera (2064 human, 656 cow and 171 dear specimens) evidenced almost the absence of immunity among the studied populations of the tundra and forest tundra zones. Certain positive samples observed in the northern taiga region could be explained by the infection gained in areas situated more to the south. Among the middle taiga human populations the immunity reached 4.9 per cent.

Animals↗
PubMed2005

Performance of a population-based cardiac risk stratification tool in Asian patients with chest pain.

OBJECTIVES: Most contemporary cardiac risk stratification tools have been derived and validated in mixed-race populations. Their validity in single-race populations has not been tested. The authors sought to compare the performance of a risk stratification tool between a mixed-race U.S. patient population and an Asian patient population. METHODS: This study is an analysis of data from the Internet Tracking Registry for Acute Coronary Syndromes (i(*)trACS) registry of patients with chest pain presenting to the emergency departments of eight U.S. centers and one site in Singapore. The Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) was computed for included patients, and its performance in predicting acute coronary syndrome (ACS) was compared between patients from the United States and Singapore. RESULTS: Of the 11,991 included patients, 1,120 experienced ACS. Although the ACI-TIPI demonstrated similar accuracy among groups (area under the curve, 0.729 [U.S.] vs. 0.719 [Singapore]; p = 0.5611), sensitivity and specificity were different when equal ACI-TIPI thresholds were considered. Recreating the logistic regression models used to create the ACI-TIPI showed similar results between the derived parameters and the parameters estimated for the U.S. group. In contrast, age older than 50 years (log-odds ratio [LOR], 0.107; 95% confidence interval [CI] = 0.518 to 0.713), male gender (LOR, 0.487; 95% CI = 0.149 to 1.122), and chest pain as a primary complaint (LOR, 0.237; 95% CI = 0.139 to 0.613) had little predictive power in patients from Singapore. CONCLUSIONS: Differences exist in presentation and factors associated with ACS among patients from the United States and Singapore that may affect the performance of risk stratification tools. These findings suggest that cardiac clinical decision rules need international validation.

Acute Disease↗
PubMed2002

The Framingham prediction rule is not valid in a European population of treated hypertensive patients.

BACKGROUND: Stratification of population groups according to cardiovascular risk level is recommended for primary prevention. OBJECTIVE: To assess whether the Framingham models could accurately predict the absolute risk of coronary heart disease (CHD) and stroke in a large cohort of middle-aged European patients with hypertension, and rank individual patients according to actual risk. DESIGN: A prospective cohort study comparing the actual risk with that predicted by either the Framingham equations or models derived from the INSIGHT study. PATIENTS AND SETTING: From the INSIGHT prospective trial, conducted in eight countries of Western Europe and Israel, we selected 4407 European patients younger than 75 years without previous cardiovascular events. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Major cardiovascular events. RESULTS: In this population (45% men, mean age 64.1 years), 124 (2.8%) patients had CHD and 96 (2.2%) had strokes after a median follow-up of 3.7 years. Overestimation of absolute CHD risk by the Framingham equation was observed in all countries (from 2% in the UK to 7% in France), whereas predicted risk of stroke was close to the actual risk. However, patients in the highest risk quintile within each country had a threefold greater risk of a cardiovascular event than those in the lowest quintile. CONCLUSIONS: The Framingham models should not be used to predict absolute CHD risk in the European population as a whole. However, these models may be used within each country, provided that cut-off points defining high-risk patients have been determined within each country.

Age Factors↗
PubMed2003

Comparison of plasma fibrinogen by Clauss, prothrombin time-derived, and immunonephelometric assays in a general population: implications for risk stratification by thirds of fibrinogen.

There is strong evidence from meta-analyses of prospective epidemiological studies that increasing plasma fibrinogen levels are associated with increasing risk of ischaemic heart disease. It has been suggested that categorization of plasma fibrinogen by thirds of the population distribution be added to cardiovascular risk prediction equations. However, the heterogeneity of plasma fibrinogen and the resulting discrepancies between commonly performed assays may lead to differences in both mean levels and distributions, and in categorizations of populations by thirds. We therefore compared three commonly performed routine fibrinogen assays in a random population sample of 1373 men and women aged 25-64 years in the fourth World Health Organization MONICA survey in north Glasgow. The two assays of clottable fibrinogen (von Clauss and prothrombin time derived) showed similar mean values and distributions, whereas the immunonephelometric assay showed lower mean values. There was significant disagreement between all three assays in categorization of thirds of population fibrinogen distribution (kappa statistic, 0.64 von Clauss versus prothrombin time derived, 0.46 von Clauss versus immunonephelometric, and 0.51 prothrombin time derived versus immunonephelometric). We conclude that further standardization of plasma fibrinogen assays is desirable for ischaemic heart disease risk stratification, and that further studies of the causes and clinical significance of discrepancies between fibrinogen assays in the general population are indicated.

Adult↗
PubMed2006

Application of an African Ancestry Index as a genomic control approach in a Brazilian population.

Ten ancestry informative markers were investigated in 101 coronary artery disease patients and 102 healthy controls from a Southern Brazilian population, in order to determine if stratification occurs in this population. The degree of African admixture detected in this population was estimated to be as high as 6%, but no differences between cases and controls were observed. Using an African Ancestry Index (AAI) that estimates admixture at the individual level it was possible to remove from the samples those individuals with evidence of African admixture. Therefore we have shown that it is possible to control for population stratification by choosing individuals, without the loss of statistical power that occurs with the use of other methods of genomic control.

Africa↗
PubMed1999

Pharmaceutically-based severity stratification of an asthmatic population.

Algorithms designed to precisely identify disease severity for a given patient within a managed care population are helpful in organizing targeted interventions. These algorithms are also attracting considerable attention within the medical research community. Several health risk screening instruments have been developed; however, these involve survey methodologies and have several shortcomings. We present a valid and efficient method for predicting healthcare resource utilization among asthmatics in an Health Maintenance Organization (HMO) population. First, various diagnosis, procedure and pharmacy billing codes were used to identify the asthmatics within the database. The screening algorithm awards points each time one of these codes is identified for an HMO member. By varying the number of points necessary to consider a patient asthmatic, the sensitivity, specificity, positive and negative predictive values of the algorithm can be adjusted. Once identified as asthmatic, subjects were then stratified into severity levels based on pharmacy data. Severity stratification was validated directly by measuring asthma-related bed days utilized during the 12 months following the date of stratification. Our identification algorithm estimated an asthma prevalence of 3.84% within the studied population, with age-specific prevalence estimates that closely mirrored previously published survey data. There was a monotonic relationship between pharmacy severity levels and inpatient resource utilization. For example, asthmatics in severity level 1 used only 92 hospital days per 1000 asthmatics in the year following characterization, while those in levels 2-5 used 133, 156, 277 and 1168 hospital days (P < 0.001), respectively. Results from this model can be used as adjusters in other predictive models or stand alone to represent a patient's severity of illness.

Adolescent↗
PubMedDate not supplied

[Population size and areas of stratification in the variational model of ecosystem].

The formulations of the variational task for finding the relative population size of species in community at a stationary stage of growth and of the theorem of stratification are given. Algorithms of finding the relative size of populations for communities consisting of two and three species consuming two or three resources were obtained. The borders of areas of stratification were described in which one, two, or three resources are limiting. For two species and two resources, the formulae of the dependence of relative size on the ratio of resources were derived, and the shape of this dependence for real requirements of species was demonstrated.

Algorithms↗
PubMed2006

Spatial stratification of soil bacterial populations in aggregates of diverse soils.

Most soil microbial community studies to date have focused on homogenized bulk soil samples. However, it is likely that many important microbial processes occur in spatially segregated microenvironments in the soil leading to a microscale biogeography. This study attempts to localize specific microbial populations to different fractions or compartments within the soil matrix. Microbial populations associated with macroaggregates and inner- versus total-microaggregates of three diverse soils were characterized using culture-independent, molecular methods. Despite their relative paucity in most surveys of soil diversity, representatives of Gemmatimonadetes and Actinobacteria subdivision Rubrobacteridae were found to be highly abundant in inner-microaggregates of most soils analyzed. By contrast, clones affiliated with Acidobacteria were found to be relatively enriched in libraries derived from macroaggregate fractions of nearly all soils, but poorly represented in inner-microaggregate fractions. Based upon analysis of 16S rRNA, active community members within microaggregates of a Georgian Ultisol were comprised largely of Gemmatimonadetes and Rubrobacteridae, while within microaggregates of a Nebraska Mollisol, Rubrobacteridae and Alphaproteobacteria were the predominant active bacterial lineages. This work suggests that microaggregates represent a unique microenvironment that selects for specific microbial lineages across disparate soils.

Actinobacteria↗
PubMed2001

Preprocedural risk stratification: identifying an appropriate population for carotid stenting.

PURPOSE: Given the uncertainties associated with carotid angioplasty and stenting, the initial assessment of the procedure may be best undertaken in a subgroup of patients at increased risk for complications with standard carotid surgery. In an effort to characterize such a subgroup, we reviewed the results of carotid endarterectomy in patients with and without significant medical comorbidity. METHODS: During a 10-year period 3061 carotid endarterectomies were performed at a single institution and entered prospectively into a registry. A high-risk patient subgroup was identified, defined by the presence of severe coronary artery disease, chronic obstructive lung disease, or renal insufficiency. The outcome of carotid endarterectomy was assessed with respect to perioperative stroke, myocardial infarction, or death, as well as the combined end point of one or more of the end points. RESULTS: The rate of the composite end point stroke/myocardial infarction/death was 3.8% in the total group of 3061 patients who underwent endarterectomy. As individual end points, the rate of stroke was 2.1%, myocardial infarction 1.2%, and death 1.1%. Among the high-risk subset, the composite end point stroke/myocardial infarction/death occurred in 7.4%. This rate was significantly greater than the corresponding rate of 2.9% in the low-risk subset (P <.0005). Similarly, the rate of stroke (3.5% vs 1.7%, P =.008) or death (4.4% vs 0.3%, P <.001) as solitary events was significantly greater in high-risk patients. CONCLUSIONS: Although carotid endarterectomy is an extremely safe procedure in most patients, results are not as favorable in a high-risk subset with severe coronary, pulmonary, or renal disease. The initial clinical evaluation of carotid stenting might best be undertaken in such a high-risk population, one that comprises patients for whom standard therapy is associated with a high rate of complications.

Angioplasty, Balloon↗