Biomedical subjects

Kijoung Song

Publications and source records attributed to Kijoung Song.

4 recordsLinked to original sources

PubMed2006

A powerful method of combining measures of association and Hardy-Weinberg disequilibrium for fine-mapping in case-control studies.

We present a new method for fine-mapping a disease susceptibility locus using a case-control design. The new method, termed the 'weighted average (WA) statistic', averages the Cochran-Armitage (CA) trend test statistic and the difference between the Hardy Weinberg disequilibrium test statistics (the HWD trend) for cases and controls. The main features of the WA statistic are that it mitigates against the weaknesses, and maintains the strong points, of both the CA trend test and the HWD trend test. To allow for the extra variance induced by population structure and cryptic relatedness, the WA statistic can be adjusted for variance inflation. Based on the results of a simulation study, when there is no population structure the WA test statistic shows good performance under a variety of genetic disease models. When there is population structure, the adjusted WA statistic maintains the correct probability of type I error. Under all genetic disease models investigated, the adjusted WA statistic has better power than the adjusted CA trend test, the HWD trend test or the product of the adjusted CA trend test and the HWD trend test statistics.

Case-Control Studies↗

PubMed2005

Fine-mapping using the weighted average method for a case-control study.

We present a new method for fine-mapping a disease susceptibility locus using a case-control design. The new method, termed the weighted average (WA) statistic, averages the Cochran-Armitage (CA) trend test statistic and the difference between the Hardy-Weinberg disequilibrium test statistic for cases and controls (the HWD trend). The main characteristics of the WA statistic are that it improves on the weaknesses, and maintains the strengths, of both the CA trend test and the HWD trend test. Data from three different populations in the Genetic Analysis Workshop 14 (GAW14) simulated dataset (Aipotu, Karangar, and Danacaa) were first subjected to model-free linkage analysis to find regions exhibiting linkage. Then, for fine-scale mapping, 140 SNPs within the significant linkage regions were analyzed with the WA test statistic on replicates of the three populations, both separately and combined. The regions that were significant in the multipoint linkage analysis were also significant in this fine-scale mapping. The most significant regions that were obtained using the WA statistic were regions in chromosome 3 (B03T3056-B03T3058, p-value < 1 x 10(-10)) and chromosome 9 (B09T8332-B09T8334, p-value 1 x 10(-6)). Based on the results of the simulated GAW14 data, the WA test statistic showed good performance and could narrow down the region containing the susceptibility locus. However, the strength of the signal depends on both the strength of the linkage disequilibrium and the heterozygosity of the linked marker.

Case-Control Studies↗

PubMed2004

Higher offspring survival among Tibetan women with high oxygen saturation genotypes residing at 4,000 m.

Here we test the hypothesis that high-altitude native resident Tibetan women with genotypes for high oxygen saturation of hemoglobin, and thus less physiological hypoxic stress, have higher Darwinian fitness than women with low oxygen saturation genotypes. Oxygen saturation and genealogical data were collected from residents of 905 households in 14 villages at altitudes of 3,800-4,200 m in the Tibet Autonomous Region along with fertility histories from 1,749 women. Segregation analysis confirmed a major gene locus with an autosomal dominant mode of inheritance for high oxygen saturation levels, associated with a 10% higher mean. Oxygen saturation genotypic probability estimators were then used to calculate the effect of the inferred oxygen saturation locus on measures of fertility, in a subsample of 691 women (20-59 years of age and still married to their first husbands, those with the highest exposure to the risk of pregnancy). The genotypic probability estimators were not significantly associated with the number of pregnancies or live births. The high oxygen saturation genotypic mean offspring mortality was significantly lower, at 0.48 deaths compared with 2.53 for the low oxygen saturation homozygote, because of lower infant mortality. Tibetan women with a high likelihood of possessing one to two alleles for high oxygen saturation had more surviving children. These findings suggest that high-altitude hypoxia is acting as an agent of natural selection on the locus for oxygen saturation of hemoglobin by the mechanism of higher infant survival of Tibetan women with high oxygen saturation genotypes.

Adolescent↗

PubMed2003

Tests for a disease-susceptibility locus allowing for an inbreeding coefficient (F).

We begin by discussing the false positive test results that arise because of cryptic relatedness and population substructure when testing a disease susceptibility locus. We extend and evaluate the Hardy-Weinberg disequilibrium (HWD) method, allowing for an inbreeding coefficient (F) in a similar way that Devlin and Roeder (1999) allowed for inbreeding in a case-control study. Then we compare the HWD measure and the common direct measure of linkage disequilibrium, both when there is no population substructure (F = 0) and when there is population substructure (F not = 0), for a single marker. The HWD test statistic gives rise to false positives caused by population stratification. These false positives can be controlled by adjusting the test statistic for the amount of variance inflation caused by the inbreeding coefficient (F). The power loss for the HWD test that arises when controlling for population structure is much less than that which arises for the common direct measure of linkage disequilibrium. However, in the multiplicative model, the HWD test has virtually no power even when allowing for non-zero F.

Computer Simulation↗