PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 8787994

Measuring gene-disease association using a general pair method.

P J Ward·C Bonaïti-Pellié
View original source ↗Export metadata ↓

Abstract

The general-pair-method (GPM) was applied to the analysis of the Problem 1 data set. GPM is a nonparametric, identity-by-state method for associating variation at a chromosomal locus with disease status. It can accommodate information from all pairs of individuals across any degree of genetic relatedness, including genetically unrelated individuals, within a single test statistic. Pairwise contrasts between members of different pedigrees, including "control" pedigrees containing no affected individuals, can therefore be exploited in order to increase the power of the test statistic. Such a strategy makes sense within the context of a candidate gene (direct association) study, where the alleles or genotypes of high disease risk are assumed to be the same ones within all families. Applied to the Problem 1 data set in this way, the GPM successfully identified the effect on disease status of locus 31 on chromosome 1, and of locus 23 on chromosome 5. The observed strength of gene-disease association at the other chromosomal loci was compatible with the null hypothesis.

Explore related subjects

Case-Control StudiesChromosome MappingGene FrequencyGenetic Diseases, InbornGenetic LinkageGenetic VariationHumansJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

P J Ward, C Bonaïti-Pellié. 1995. Measuring gene-disease association using a general pair method.. https://doi.org/10.1002/gepi.1370120627

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1997

A reevaluation of the risk for venous thromboembolism with the use of oral contraceptives and hormone replacement therapy.

BACKGROUND: There are many health benefits associated with the use or oral contraceptives (OCs) and hormone replacement therapy (HRT), but these agents are also associated with potential health risks. OBJECTIVE: To reevaluate the current practice of withholding OCs or HRT in women with previous venous thromboembolism (VTE) by critically reviewing the evidence that the use of OCs or HRT is associated with an increased risk for VTE. METHODS: A MEDLINE literature search was performed to identify studies investigating associations between OCs and VTE or HRT and VTE. Each study was rated according to methodologic quality (level 1, low potential for bias; level 2, moderate potential for bias; level 3, high potential for bias). Results were combined across studies of similar design to determine pooled risk ratios for VTE. The results from studies investigating third-generation OCs were reported separately. RESULTS: For OC studies (n = 22), the pooled risk ratios (95% confidence intervals) in case-control studies, retrospective cohort studies, prospective cohort studies, and randomized controlled trials were 3.0 (2.6-3.4), 4.8 (2.5-7.7), 2.4 (1.6-3.5), and 1.1 (0.4-2.9), respectively. In users of third-generation OCs, the pooled risk ratio (95% confidence interval) for VTE was 5.0 (2.5-7.5). No study was rated as level 1, 6 were rated as level 2, and 16 as level 3. Methodologic limitations in these studies would tend to exaggerate the risk for VTE with OC use. For HRT studies (n = 9), the pooled risk ratios (95% confidence intervals) in case-control studies, prospective cohort studies and randomized controlled trials were 2.4 (1.7-3.5), 1.7 (1.0-2.9), and 0.7 (0.3-1.6), respectively. No study was rated as level 1, 6 were rated as level 2, and 3 as level 3. CONCLUSIONS: First, an association between OC use and VTE is likely valid, but the reported risks are probably exaggerated. We estimate that users of non-third-generation OCs have a less than 3-fold increase in the risk for VTE compared with nonusers; the risk for VTE is possibly higher with the use of third-generation OCs. Second, an association between HRT use and VTE might exist; however, further investigation is required before definitive conclusions can be made.

Case-Control Studies↗
PubMed1997

Residential exposure to magnetic fields and acute lymphoblastic leukemia in children.

BACKGROUND: Previous studies found associations between childhood leukemia and surrogate indicators of exposure to magnetic fields (the power-line classification since known as "wire coding"), but not between childhood leukemia and measurements of 60-Hz residential magnetic fields. METHODS: We enrolled 638 children with acute lymphoblastic leukemia (ALL) who were under 15 years of age and were registered with the Children's Cancer Group and 620 controls in a study of residential exposure to magnetic fields generated by nearby power lines. In the subjects' current and former homes, data collectors measured magnetic fields for 24 hours in the child's bedroom and for 30 seconds in three or four other rooms and outside the front door. A computer algorithm assigned wire-code categories; based on the distance and configuration of nearby power lines, to the subjects' main residences (for 416 case patients and 416 controls) and to those where the family had lived during the mother's pregnancy with the subject (for 230 case patients and 230 controls). RESULTS: The risk of childhood ALL was not linked to summary time-weighted average residential magnetic-field levels, categorized according to a priori criteria. The odds ratio for ALL was 1.24 (95 percent confidence interval, 0.86 to 1.79) at exposures of 0.200 mu T or greater as compared with less than 0.065 mu T. The risk of ALL was not increased among children whose main residences were in the highest wire-code category (odds ratio as compared with the lowest category, 0.88; 95 percent confidence interval, 0.48 to 1.63). Furthermore, the risk was not significantly associated with either residential magnetic-field levels or the wire codes of the homes mothers resided in when pregnant with the subjects. CONCLUSIONS: Our results provide little evidence that living in homes characterized by high measured time-weighted average magnetic-field levels or by the highest wire-code category increases the risk of ALL in children.

Case-Control Studies↗