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PubMed1992

Effects of physical activity on health status in older adults. II. Intervention studies.

This review has focused on a specific part of the relationship of exercise to health. The overall evidence supporting the health benefits of exercise is substantial and has been critically reviewed recently (18, 94). Thus, the United States Preventive Services Task Force recommends that all adults exercise regularly (94). The conclusions summarized below regarding older adults do not affect this basic recommendation. There is solid evidence that exercise can improve measures of fitness in older adults, particularly strength and aerobic capacity. These exercise effects occur in chronically ill adults, as well as in healthy adults. Because physical fitness is a determinant of functional status, it is logical to ask whether exercise can prevent or improve impairments in functional status in older adults. The evidence that exercise improves functional status is promising, but inconclusive. Problems with existing studies include a lack of randomized controlled trials, a lack of evidence that effects of exercise can be sustained over long periods of time, inadequate statistical power, and failure to target physically unfit individuals. Existing studies suggest that exercise may produce improvements in gait and balance. Arthritis patients may experience long-term functional status benefits from exercise, including improved mobility and decreased pain symptoms. Nonrandomized trials suggest exercise promotes bone mineral density and thereby decreases fracture risk. Recent studies have generally concluded that short-term exercise does not improve cognitive function. Yet the limited statistical power of these studies does not preclude what may be a modest, but functionally meaningful, effect of exercise on cognition. Future research, beyond correcting methodologic deficiencies in existing studies, should systematically study how functional status effects of exercise vary with the type, intensity, and duration of exercise. It should address issues in recruiting functionally impaired older adults into exercise studies, issues in promoting long-term adherence to exercise, and whether the currently low rate of exercise-related injuries in supervised classes can be sustained in more cost-effective interventions that require less supervision.

Activities of Daily Living↗
PubMed1999

Statistical analysis of adaptive response in sister chromatid exchanges in human lymphocytes after treatment with very low and extremely low doses of N-methyl-N'-nitro-N-nitrosoguanidine using a study design to control variability.

Previous studies have been interpreted as suggesting that low concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) have an adaptive effect in the cultured lymphocytes of responsive donors (that is, the cells are protected against the mutagenic effects of a subsequent challenge with a higher concentration of MNNG). The objectives of the present study were to investigate, under stringent experimental conditions, whether a protective effect exists at very low and extremely low doses of MNNG (10(-8) and 10(-24) M, respectively). Peripheral blood lymphocytes from a donor considered responsive in a previous study were stimulated to divide and were cultured under standard conditions. Pre-adaptive treatments with dilutions of MNNG were added to the cultures repeatedly before a challenge treatment with MNNG. Bromodeoxyuridine was added at the same time as the challenge treatment and, following mitotic arrest, cells were differentially stained so that the number of sister chromatid exchanges (SCEs) could be counted. The study was designed to address potential criticisms of earlier studies which did not include replicate cultures. Samples of blood were divided into two identical batches for independent processing. Five replicate cultures were prepared for each combination of pre-adaptive and challenge treatments in each batch. The complete experiment was repeated to provide a further test of the consistency of results. Five replicates per treatment combination were chosen in an attempt to provide an experiment of adequate statistical power. Considerable precautions were taken to minimise the effect of factors outside experimental control on the results. Scoring was done by three scorers. In order to minimise inter-scorer variation, 240 cells were scored at each treatment observation (five cells per-scorer, three scorers per culture, four cultures per batch, two batches per experiment and two experiments). The study was designed in this way to take account of the sources of variability to ensure that any response obtained would exceed that obtainable by experimental variability alone. A high level of quality assurance monitoring was undertaken throughout the investigation. Two measures of SCE induction were used: (i) the mean frequency of SCEs; (iii) proportion of cells with at least 20 SCEs. In both experiments, the challenge concentration of MNNG significantly increased SCE frequency. There were, however, highly significant differences between the two experiments. The proportion of high frequency cells (HFCs) in Experiment 1 was increased significantly; the proportion of HFCs was also increased in Experiment 2, but the increase was not statistically significant. The pre-adaptive concentrations of MNNG included an extremely low dilution of 6.8 x 10(-24) M and a very low dilution of 6.8 x 10(-8) M in Experiment 1 and 1.4 x 10(-7) M in Experiment 2. The various pre-adaptive concentrations used had no consistent protective effect against the SCE-inducing capacity of the challenge concentration of MNNG of 6.8 x 10(-6) M. It is concluded that an adaptive response to the alkylating agent MNNG could not be demonstrated in cultured human lymphocytes. Neither a very low nor an extremely low dilution of MNNG elicited an adaptive response in terms of SCE induction (measured either as SCE frequency or as proportion of HFCs). This is in contradiction to previous reports published by us and other groups. This study was carefully designed with large numbers of replicates, a preliminary statistical power calculation, predefined comparisons and extensive quality assurance at each treatment administration. Despite these precautions the variability between scorers and between batches was much larger than anticipated. This resulted in some statistically significant differences, but these are likely to be false positives. Our findings indicate the need for such methodological refinement in human cell adaptive response studies.

Carcinogens↗
PubMedDate not supplied

A comparison of bivariate and univariate QTL mapping in livestock populations.

This study presents a multivariate, variance component-based QTL mapping model implemented via restricted maximum likelihood (REML). The method was applied to investigate bivariate and univariate QTL mapping analyses, using simulated data. Specifically, we report results on the statistical power to detect a QTL and on the precision of parameter estimates using univariate and bivariate approaches. The model and methodology were also applied to study the effectiveness of partitioning the overall genetic correlation between two traits into a component due to many genes of small effect, and one due to the QTL. It is shown that when the QTL has a pleiotropic effect on two traits, a bivariate analysis leads to a higher statistical power of detecting the QTL and to a more precise estimate of the QTL's map position, in particular in the case when the QTL has a small effect on the trait. The increase in power is most marked in cases where the contributions of the QTL and of the polygenic components to the genetic correlation have opposite signs. The bivariate REML analysis can successfully partition the two components contributing to the genetic correlation between traits.

Animals↗
PubMed2005

A family study in Oman: large, consanguineous, polygamous Omani Arab pedigrees.

OBJECTIVE: To establish a suitable human model for the study of the genetics of complex diseases. METHODS: We have selected an Omani Arab population to provide the statistical power required to study the genetics of complex diseases with confidence. This model consists of five multigenerational highly inbred pedigrees, descending from a small number of founders just a few generations ago with environmental homogeneity, restricted geographical distribution, detailed records and well-ascertained and -validated pedigrees. Stringent criteria were adopted for defining the phenotypes of hypertension, diabetes mellitus, dyslipidemias and obesity. The SOLAR genetic software package was used to draw the pedigree structure. RESULTS: Outstanding statistical power to detect susceptibility loci was obtained. CONCLUSIONS: This model represents a large homogeneous human family-based population for the study of genetic and environmental factors contributing to complex diseases.

Consanguinity↗
PubMed2004

Effects of perfluorooctane sulfonate and perfluorooctanoic acid on the zooplanktonic community.

This comparative survey summarizes six individual studies on the ecological effects of two common perfluorinated surfactants, PFOS and PFOA, on zooplankton. We compare the test designs and quantify the relative sensitivity and statistical power (1-beta > or = 0.8). The survey compares 30-L indoor microcosm to 12,000-L outdoor microcosm experiments, with 225-mL single species laboratory tests as reference. By this we elucidate the extrapolation of ecological effects in space and complexity. Generally, zooplankton had lower tolerance toward PFOS than toward PFOA. With increasing concentrations the zooplankton community became simplified toward more robust rotifer species, which, as an indirect effect, increased their abundance due to a shift in competition and predation. The statistical power of the designs exhibits inverse proportionality between complexity and realism, indoor microcosm>outdoor microcosm. Surprisingly, the 30-L study had a lower LOEC value for Daphnia magna than the laboratory chronic test, indicating that D. magna and D. pulicaria were not the most sensitive species and that laboratory tests are not always conservative relative to microcosm experiments. Food scarcity due to phytotoxicity was not the reason for the difference.

Alkanesulfonic Acids↗
PubMed2003

Comparison of stratification and adaptive methods for treatment allocation in an acute stroke clinical trial.

Achieving balance on prognostic factors between treatment groups in a clinical trial is important to ensure that any observed treatment effect may be attributed to the treatment itself. Improving the balance on prognostic factors also potentially increases the statistical power attained in a trial. Substantial imbalances may occur by chance if simple randomization is used. Allocation of the treatment according to stratified random blocks based on clinical features is the conventional approach to obtain treatment groups that are as similar as possible. An alternative approach, known as minimization (or more generally as adaptive stratification), has also been proposed. We assessed the feasibility of adaptive stratification in the context of a clinical trial of insulin to control plasma glucose level following acute stroke. We determined suitable settings for the parameters in the adaptive stratification procedure by simulation studies. Specifically, we assessed: the optimal probability for allocating a patient to the preferred (leading to least imbalance on prognostic factors) treatment group; the number of variables that could be incorporated in the adaptive stratification algorithm; the weighting that should be given to each variable; and whether interactions between variables should be included. We then compared the statistical power, across a range of simulated treatment effects, between trials where treatments were allocated by stratified random blocks and by adaptive stratification. Finally, we considered the importance of the method of analysis in realizing the gain in power which may potentially be achieved by allocating treatments using stratified random blocks or adaptive stratification.

Aged↗
PubMed1987

Treatment of acute pancreatitis. Comparison of animal and human studies.

In this review, we compared the outcome of 25 studies of experimentally induced pancreatitis in animals with 13 studies of human acute pancreatitis in which the same therapeutic agents were used (aprotinin, glucagon, 5-fluorouracil, somatostatin, peritoneal lavage). Whereas 81% of the animal studies had a positive outcome (improvement in survival), only 7.7% of the human studies showed a positive outcome on survival. Most animal studies suffered from a protocol in which treatment was not significantly delayed after induction of acute pancreatitis. Of the 12 human studies that showed no effect of treatment on survival, none had sufficient statistical power (1 - beta error) for the investigators to have confidence in the negative outcomes. This was due to the fact that the studies had too few patients or that the event rates in the untreated populations were too low. Only five of the human studies reported the complication rates of acute pancreatitis in patients who did not die of their disease. Treatment (by any agent) did not improve the complication rate in these studies, but only one of the five reports had sufficient statistical power for the investigators to have confidence in these negative results. Large multicenter studies with sufficient numbers of patients with severe pancreatitis (high mortality and complication rates) are needed to evaluate new therapies in this disease.

Acute Disease↗
PubMed1995

Limitations of head-up tilt test for evaluating the efficacy of therapeutic interventions in patients with vasovagal syncope: results of a controlled study of etilefrine versus placebo.

OBJECTIVES: This study assessed the efficacy of oral etilefrine (10 mg three times a day) in preventing a positive response to head-up tilt testing. BACKGROUND: Previous reports have suggested that oral etilefrine can be effective either in preventing a positive response to head-up tilt testing or in reducing syncopal recurrences in patients with vasovagal syncope. Up to now most studies assessing drug therapy in these patients have been uncontrolled. METHODS: This was a randomized double-blind crossover study of etilefrine versus placebo in 30 consecutive patients with syncope and a baseline positive head-up tilt test. After the first test, patients had no treatment for 3 days and were randomized to receive etilefrine or placebo for 4 additional days. They underwent tilt testing under treatment and again after 3 days of washout; they then received the alternative treatment for 4 days, and a third test was performed. RESULTS: Head-up tilt test results were negative in 13 (43%) patients with etilefrine and 15 (50%) with placebo (p = NS). Therefore, the statistical power of the study was only 10%. The rate of positive responses decreased with repeated testing irrespective of the assigned treatment: A positive response was obtained during the second head-up tilt test in 20 patients (10 with placebo, 10 with etilefrine) but in only 12 during the third (7 with etilefrine, 5 with placebo) (p < 0.05). CONCLUSIONS: Oral etilefrine (10 mg three times a day) was not superior to placebo in preventing a positive response to head-up tilt testing. Despite a low statistical power, the high rate of negative response with placebo (50%) suggests that controlled trials are needed to assess the real efficacy of any treatment in patients with vasovagal syncope.

Administration, Oral↗
PubMed1995

Blood transfusion and septic complications after hip replacement surgery.

BACKGROUND: The purpose of this study was to address some methodologic issues that might help explain the disagreement between the findings of earlier reports on the presumed association between allogeneic blood transfusion and the increased postoperative infection rates seen in orthopedic surgery patients. STUDY DESIGN AND METHODS: A retrospective review of the incidence of postoperative septic complications in 367 patients from Olmsted County, Minnesota, who underwent 420 elective total hip arthroplasties between 1986 and 1993, was conducted. The infection rates in the exposed patients (those who had perioperatively received allogeneic blood components only or allogeneic and autologous blood components) were compared with those in the untransfused patients and patients who received only autologous blood. The study had sufficient statistical power to detect a deleterious effect of allogeneic blood transfusion equal to the 2.8-fold effect observed in a recent randomized clinical trial of patients undergoing elective abdominal surgery. RESULTS: There was no association of allogeneic blood transfusion with postoperative infection (p = 0.226). Nineteen infections occurred in 201 exposed patients (9.5%), as compared to 14 infections in 219 unexposed patients (6.4%). CONCLUSION: Allogeneic blood transfusion does not increase the incidence of post-operative septic complications in patients undergoing elective total hip arthroplasty, at least to the extent that the statistical power of this study allowed the determination.

Bacterial Infections↗
PubMedDate not supplied

Influence of sampling on the reproducibility of ovarian follicle counts in mouse toxicity studies.

Different ovarian follicle counting procedures were investigated to reduce labor while retaining statistical power. Intact ovaries of untreated CD-1 mice (20/group) from National Toxicology Program Reproductive Assessment by Continuous Breeding (RACB) studies were serially sectioned at 6 microm. Mean numbers of small and growing follicles were used to assess sampling efficiency. In 10 mice per group, comparisons were made between 10% nonrandom samples from every 10th section starting at either the first or sixth section having follicles (approximately 40 sections per ovary). These 10% counts were compared with 5% (20 sections) and 20% (80 sections) nonrandom samples and with 1% (4 sections), 5%, or 10% random samples from the same 10 animals. For two studies, a 10% nonrandom sample was analyzed from 20 mice per group. Follicle counts for each group were comparable regardless of the sampling paradigm. Four to 10 animals provided 90% confidence that a 20% difference in mean counts would be detected. The 1% sample had a larger error term and, thus, slightly reduced statistical power. These data suggest that follicle counts from 1% or 5% random samples may provide a suitable screen for ovarian toxicity.

Animals↗
PubMed2002

Feasibility of the physiological cost index as an outcome measure for the assessment of energy expenditure during walking.

OBJECTIVE: To determine if the Physiological Cost Index (PCI) can be recommended as an outcome measure in clinical trials. DESIGN: Three assessments were performed, 2 with shoes, 1 without. The difference between walking with shoes and walking barefoot was used to study the ability of the PCI to detect a change in the criterion standard. SETTING: A research department affiliated with a rehabilitation hospital in the Netherlands. PARTICIPANTS: Twelve children with cerebral palsy. INTERVENTIONS: During the first and third assessments, the children walked with shoes. During the intermediate assessment, the children walked without shoes. MAIN OUTCOME MEASURE: Breath-by-breath oxygen uptake, heart rate (HR), and walking speed were measured at a self-selected comfortable speed. Oxygen cost (EO(2)) and the PCI were subsequently calculated offline. Feasibility judgments were made regarding the ability of the PCI to detect changes in a criterion standard and the statistical power of the outcome measure. RESULTS: Pearson correlation coefficients were.66 and.62 for HR(walking)-HR(baseline) and HR(walking), respectively. The smallest detectable difference of the PCI and EO(2) were 69% and 32%, respectively. A difference of at least 69% or 32% should be found before one can conclude a difference with a certainty of 95%. CONCLUSIONS: The reproducibility of the PCI and the ability to show small differences in EO(2) were moderate. Subtracting HR(baseline) when calculating the PCI is probably not useful because it only increased within-subject variability. With respect to statistical power of a new clinical trial, we recommend using EO(2) instead of the PCI.

Cerebral Palsy↗
PubMed2007

Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events.

For rare outcomes, meta-analysis of randomized trials may be the only way to obtain reliable evidence of the effects of healthcare interventions. However, many methods of meta-analysis are based on large sample approximations, and may be unsuitable when events are rare. Through simulation, we evaluated the performance of 12 methods for pooling rare events, considering estimability, bias, coverage and statistical power. Simulations were based on data sets from three case studies with between five and 19 trials, using baseline event rates between 0.1 and 10 per cent and risk ratios of 1, 0.75, 0.5 and 0.2. We found that most of the commonly used meta-analytical methods were biased when data were sparse. The bias was greatest in inverse variance and DerSimonian and Laird odds ratio and risk difference methods, and the Mantel-Haenszel (MH) odds ratio method using a 0.5 zero-cell correction. Risk difference meta-analytical methods tended to show conservative confidence interval coverage and low statistical power at low event rates. At event rates below 1 per cent the Peto one-step odds ratio method was the least biased and most powerful method, and provided the best confidence interval coverage, provided there was no substantial imbalance between treatment and control group sizes within trials, and treatment effects were not exceptionally large. In other circumstances the MH OR without zero-cell corrections, logistic regression and the exact method performed similarly to each other, and were less biased than the Peto method.

Analysis of Variance↗
PubMed1997

Y-chromosome effects on Drosophila geotaxis interact with genetic or cytoplasmic background.

Previously, all of the major fruit fly, Drosophila melanogaster, chromosomes (I, II and III) have been shown to be associated with geotaxis, but the Y chromosome has not. Using two methods (back-crossing and chromosome substitution), Y chromosomes from lines that have evolved stable, extreme expressions of geotaxis were placed into different genetic and cytoplasmic backgrounds to test the resulting males for geotaxis. The results of the back-crossing do not support the interpretation of Y-chromosome effects on geotaxis. These tests do not have sufficient statistical power, however, to detect small genetic effects. In the chromosome substitution experiment, the geotaxis-line Y chromosomes were placed into high- and low-selected lines, Canton-S and Champaign wild-type backgrounds. The results of the chromosome substitution experiment provide evidence for a Y-chromosome effect on geotaxis in selected geotaxis lines, but not in wild-type stock, backgrounds. These results suggest that the Y chromosome has a small effect on geotaxis, whose detection depends on genetic and/or cytoplasmic background. The implications of these results are discussed for behaviour genetic analysis of D. melanogaster and for issues of statistical power in detecting small genetic effects.

Animals↗
PubMed2006

G-protein beta3 subunit gene variant (C825T) is unlikely to have a significant influence on serum total cholesterol level in Japanese workers.

We investigated the association between hypercholesterolemia or serum total cholesterol level and the C825T polymorphism in the G-protein ss3 subunit gene in Japanese workers using multivariate analysis to control possible confounding factors. The study subjects were 1,452 males and 1,169 females selected from 3,834 males and 2,591 females. Hypercholesterolemia was classified as either a total serum cholesterol $5.7 mmol/L (220 mg/dL) or taking lipid-lowering medication. The statistical power of the study was estimated as 99.9% based on total cholesterol levels of previous significant studies in Caucasians and Japanese. The genotype distributions in males with hypercholesterolemia (CC = 78, CT = 154, TT = 78) and females (CC = 60, CT = 137, TT = 52) were not significantly different from normal males (CC = 280, CT = 595, TT = 267) or females (CC = 234, CT = 501, TT = 185). Allele distributions also were not significantly different in either sex. Logistic regression analysis of hypercholesterolemia data and analysis of variance, t-test and multiple regression of serum total cholesterol data demonstrated no significant relationship with the C825T genotype. Despite sufficient statistical power, this study did not demonstrate a significant influence of C825T on hypercholesterolemia or serum total cholesterol level. The targeting of this polymorphism therefore is unlikely to be beneficial in preventing hypercholesterolemia in the general Japanese population.

Alleles↗
PubMed2006

Susceptibility of biallelic haplotype and genotype frequencies to genotyping error.

With the availability of fast genotyping methods and genomic databases, the search for statistical association of single nucleotide polymorphisms with a complex trait has become an important methodology in medical genetics. However, even fairly rare errors occurring during the genotyping process can lead to spurious association results and decrease in statistical power. We develop a systematic approach to study how genotyping errors change the genotype distribution in a sample. The general M-marker case is reduced to that of a single-marker locus by recognizing the underlying tensor-product structure of the error matrix. Both method and general conclusions apply to the general error model; we give detailed results for allele-based errors of size depending both on the marker locus and the allele present. Multiple errors are treated in terms of the associated diffusion process on the space of genotype distributions. We find that certain genotype and haplotype distributions remain unchanged under genotyping errors, and that genotyping errors generally render the distribution more similar to the stable one. In case-control association studies, this will lead to loss of statistical power for nondifferential genotyping errors and increase in type I error for differential genotyping errors. Moreover, we show that allele-based genotyping errors do not disturb Hardy-Weinberg equilibrium in the genotype distribution. In this setting we also identify maximally affected distributions. As they correspond to situations with rare alleles and marker loci in high linkage disequilibrium, careful checking for genotyping errors is advisable when significant association based on such alleles/haplotypes is observed in association studies.

Alleles↗
PubMed1997

Validation and calibration of dietary intake measurements in the EPIC project: methodological considerations. European Prospective Investigation into Cancer and Nutrition.

The statistical power of prospective studies on diet in relation to chronic disease risk can be improved by maximizing the variation in true intake levels actually distinguished--or 'predicted'--by dietary questionnaire assessments collected at baseline. This can be achieved by 1) developing a questionnaire method that provides measurements with the smallest possible random errors, thus maximizing the correlation of measured with true habitual intake levels; and 2) increasing the between-person variation in true dietary intake levels when combining multiple cohorts in populations with diverse consumption patterns. The first approach implies that, during the development or selection of the questionnaire method, correlations between measurements and true intake levels can be monitored; the second approach requires adjustment for between-centre differences in over--or underestimation of dietary questionnaire measurements. Besides optimizing the statistical power, it is important that the magnitude of the predicted variation in true intake level is estimated accurately, so as to allow unbiased estimations of relative risks. To meet these various objectives, substudies must be conducted for the 'validation' or 'calibration' of dietary questionnaire assessments, by comparison with additional measurements that have independent sources of error. This paper reviews the methodological considerations underlying the design and implementation of such substudies in the EPIC project, a collaborative multicentre study in nine Western European countries.

Diet↗
PubMed2006

A comparison of two dietary instruments for evaluating the fat-breast cancer relationship.

BACKGROUND: Previous research suggests food diaries may be more efficient than food frequency questionnaires (FFQ) in detecting a dietary fat-breast cancer relationship. We assessed this further using 4 day food records (FRs) and FFQs in a large sample. METHODS: Participants were from the non-intervention group of the dietary modification component of the Women's Health Initiative Clinical Trial: 603 breast cancer cases and 1206 controls matched on age, clinic, and length of follow-up. Relative risks (RRs) were estimated using unconditional logistic regression, adjusted for confounders and for the selection into the trial of women with an FFQ report exceeding 32% calories from fat. Direct comparison of the statistical power of the two instruments used the standardized log RR. An alternative analysis after removing subjects with missing covariate data was also conducted. RESULTS: The RR estimate for breast cancer in the top quintile of total fat intake, adjusted for confounders and total energy, was 1.82 (P for trend 0.02) for the FR but 0.67 for the FFQ (P for trend 0.24). Following adjustment for selection, estimates were 2.09 (P for trend 0.008) for the FR (alternative: 2.54, P for trend 0.006) and 1.71 (P for trend 0.18) for the FFQ (alternative: 1.24, P for trend 0.41). Similar results were seen for fat subtypes, particularly unsaturated fats. Comparisons showed higher statistical power for the FR than the FFQ (e.g. total fat, P = 0.08: alternative P = 0.01). CONCLUSIONS: Alternative instruments, such as FRs, may be preferable to FFQs for evaluating diet-disease relationships in cohort studies. The results support a positive association between dietary fat and breast cancer.

Aged↗
PubMed1997

Mapping genes underlying ethnic differences in disease risk by linkage disequilibrium in recently admixed populations.

Where recent admixture has occurred between two populations that have different disease rates for genetic reasons, family-based association studies can be used to map the genes underlying these differences, if the ancestry of the alleles at each locus examined can be assigned to one of the two founding populations. This article explores the statistical power and design requirements of this approach. Markers suitable for assigning the ancestry of genomic regions could be defined by grouping alleles at closely spaced microsatellite loci into haplotypes, or generated by representational difference analysis. For a given relative risk between populations, the sample size required to detect a disease locus that accounts for this relative risk by linkage-disequilibrium mapping in an admixed population is not critically dependent on assumptions about genotype penetrances or allele frequencies. Using the transmission-disequilibrium test to search the genome for a locus that accounts for a relative risk of between 2 and 3 in a high-risk population, compared with a low-risk population, generally requires between 150 and 800 case-parent pairs of mixed descent. The optimal strategy is to conduct an initial study using markers spaced at < or = 10 cM with cases from the second and third generations of mixed descent, and then to map the disease loci more accurately in a subsequent study of a population with a longer history of admixture. This approach has greater statistical power than allele-sharing designs and has obvious applications to the genetics of hypertension, non-insulin-dependent diabetes, and obesity.

Alleles↗