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Results for “association testing”

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At least 289 records · Page 16Linked to original sources
PubMed2006

Testing association between LRRK2 and Parkinson's disease and investigating linkage disequilibrium.

BACKGROUND: We and others recently identified the gene underlying PARK8 linked Parkinson's disease (PD). This gene, LRRK2, contains mutations that cause an autosomal dominant PD, including a mutation, G2019S, which is the most common PD causing mutation identified to date. Common genetic variability in genes that contain PD causing mutations has previously been implicated as a risk factor for typical sporadic disease. METHODS: We undertook a case-control association analysis of LRRK2 in two independent European PD cohorts using 31 tagging single nucleotide polymorphisms (tSNPs) and five potentially functional SNPs. To assess the structure of this locus in different populations, we have performed linkage disequilibrium (LD) analysis using these variants in a human diversity panel. RESULTS: We show that common genetic variability in LRRK2 is not associated with risk for PD in the European populations studied here. We also show inter-population variability in the strength of LD across this locus. CONCLUSIONS: To our knowledge this is the first comprehensive analysis of common variability within LRRK2 as a risk factor for PD.

Adult↗
PubMed2001

Association tests in nuclear families.

We present a conditional likelihood approach for testing linkage disequilibrium in nuclear families having multiple affected offspring. The likelihood, conditioned on the identity-by-descent (IBD) structure of the sibling genotypes, is unaffected by familial correlation in disease status that arises from linkage between a marker locus and the unobserved trait locus. Two such conditional likelihoods are compared: one that conditions on IBD and phase of the transmitted alleles and a second which conditions only on IBD of the transmitted alleles. Under the log-additive model, the first likelihood is equivalent to the allele-counting methods proposed in the literature. The second likelihood is valid under the added assumption of equal male and female recombination fractions. In a simulation study, we demonstrated that in sibships having two or three affected siblings the score test from each likelihood had the correct test size for testing disequilibrium. They also led to equivalent power to detect linkage disequilibrium at the 5% significance level.

Computer Simulation↗
PubMed2004

Optimal designs for linkage disequilibrium mapping and candidate gene association tests in livestock populations.

Simulation was used to evaluate the performance of different selective genotyping strategies when using linkage disequilibrium across large half-sib families to position a QTL within a previously defined genomic region. Strategies examined included standard selective genotyping and different approaches of discordant and concordant sib selection applied to arbitrary or selected families. Strategies were compared as a function of effect and frequency of QTL alleles, heritability, and phenotypic expression of the trait. Large half-sib families were simulated for 100 generations and 2% of the population was genotyped in the final generation. Simple ANOVA was applied and the marker with the greatest F-value was considered the most likely QTL position. For traits with continuous phenotypes, genotyping the most divergent pairs of half-sibs from all families was the best strategy in general, but standard selective genotyping was somewhat more precise when heritability was low. When the phenotype was distributed in ordered categories, discordant sib selection was the optimal approach for positioning QTL for traits with high heritability and concordant sib selection was the best approach when genetic effects were small. Genotyping of a few selected sibs from many families was generally more efficient than genotyping many individuals from a few highly selected sires.

Alleles↗
PubMed2006

Early diagnosis of congestive heart failure: clinical utility of B-type natriuretic peptide testing associated with Doppler echocardiography.

OBJECTIVE: B-type natriuretic peptide (BNP) has emerged as an important diagnostic serum marker of congestive heart failure (CHF). The aim of this study was to evaluate whether BNP measurement associated with echocardiography could effectively stratify patients with new symptoms as part of a cost-effective heart failure programme based on cooperation between hospital cardiologists and primary care physicians. METHODS: Patients were referred to the cardiology clinic by general practitioners in case of clinical suspect of CHF. All patients underwent clinical examination, transthoracic echocardiography and plasma determination of BNP. Systolic dysfunction was defined as a left ventricular ejection fraction < 45%; diastolic dysfunction was defined as a preserved systolic function with signs of diastolic impairment. RESULTS: Three hundred and fifty-seven subjects were examined (50% males, mean age 73 years). BNP concentration was 469 +/- 505 pg/ml in the 240 patients diagnosed with CHF, compared with 43 +/- 105 pg/ml in the 117 patients without CHF (P = 0.001). CHF patients were grouped into those with diastolic dysfunction (n = 110; BNP 373 +/- 335 pg/ml), systolic dysfunction (n = 108; BNP 550 +/- 602 pg/ml), and both systolic and diastolic dysfunction (n = 22; BNP 919 +/- 604 pg/ml). At receiver operating characteristic analysis, the optimal BNP cut-off level for diagnosing CHF was 80 pg/ml (sensitivity 84%, specificity 91%). According to cost analysis, this cut-off level might provide a cost saving of 31% without affecting diagnostic accuracy. CONCLUSIONS: In patients referred by general practitioners for suspected CHF, plasma BNP levels might help to stratify subjects into different groups of cardiac dysfunction.

Aged↗