Biomedical subjects

Joshua Millstein

Publications and source records attributed to Joshua Millstein.

6 recordsLinked to original sources

PubMed2006

Health effects of the 2003 Southern California wildfires on children.

RATIONALE: In late October 2003, Southern California wildfires burned more than 3,000 km2. The wildfires produced heavy smoke that affected several communities participating in the University of Southern California Children's Health Study (CHS). OBJECTIVES: To study the acute effects of fire smoke on the health of CHS participants. METHODS: A questionnaire was used to assess smoke exposure and occurrence of symptoms among CHS high-school students (n = 873; age, 17-18 yr) and elementary-school children (n = 5,551; age, 6-7 yr), in a total of 16 communities. Estimates of particulate matter (PM10) concentrations during the 5 d with the highest fire activity were used to characterize community smoke level. MAIN RESULTS: All symptoms (nose, eyes, and throat irritations; cough; bronchitis; cold; wheezing; asthma attacks), medication usage, and physician visits were associated with individually reported exposure differences within communities. Risks increased monotonically with the number of reported smoky days. For most outcomes, reporting rates between communities were also associated with the fire-related PM10 levels. Associations tended to be strongest among those without asthma. Individuals with asthma were more likely to take preventive action, such as wearing masks or staying indoors during the fire. CONCLUSIONS: Exposure to wildfire smoke was associated with increased eye and respiratory symptoms, medication use, and physician visits.

Adolescent↗

PubMed2005

Identifying susceptibility genes by using joint tests of association and linkage and accounting for epistasis.

Simulated Genetic Analysis Workshop 14 data were analyzed by jointly testing linkage and association and by accounting for epistasis using a candidate gene approach. Our group was unblinded to the "answers." The 48 single-nucleotide polymorphisms (SNPs) within the six disease loci were analyzed in addition to five SNPs from each of two non-disease-related loci. Affected sib-parent data was extracted from the first 10 replicates for populations Aipotu, Kaarangar, and Danacaa, and analyzed separately for each replicate. We developed a likelihood for testing association and/or linkage using data from affected sib pairs and their parents. Identical-by-descent (IBD) allele sharing between sibs was explicitly modeled using a conditional logistic regression approach and incorporating a covariate that represents expected IBD allele sharing given the genotypes of the sibs and their parents. Interactions were accounted for by performing likelihood ratio tests in stages determined by the highest order interaction term in the model. In the first stage, main effects were tested independently, and in subsequent stages, multilocus effects were tested conditional on significant marginal effects. A reduction in the number of tests performed was achieved by prescreening gene combinations with a goodness-of-fit chi square statistic that depended on mating-type frequencies. SNP-specific joint effects of linkage and association were identified for loci D1, D2, D3, and D4 in multiple replicates. The strongest effect was for SNP B03T3056, which had a median p-value of 1.98 x 10(-34). No two- or three-locus effects were found in more than one replicate.

Databases, Genetic↗

PubMed2005

A testing framework for identifying susceptibility genes in the presence of epistasis.

An efficient testing strategy called the "focused interaction testing framework" (FITF) was developed to identify susceptibility genes involved in epistatic interactions for case-control studies of candidate genes. In the FITF approach, likelihood-ratio tests are performed in stages that increase in the order of interaction considered. Joint tests of main effects and interactions are performed conditional on significant lower-order effects. A reduction in the number of tests performed is achieved by prescreening gene combinations with a goodness-of-fit chi2 statistic that depends on association among candidate genes in the pooled case-control group. Multiple testing is accounted for by controlling false-discovery rates. Simulation analysis demonstrated that the FITF approach is more powerful than marginal tests of candidate genes. FITF also outperformed multifactor dimensionality reduction when interactions involved additive, dominant, or recessive genes. In an application to asthma case-control data from the Children's Health Study, FITF identified a significant multilocus effect between the nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase gene (NQO1), myeloperoxidase gene (MPO), and catalase gene (CAT) (unadjusted P = .00026), three genes that are involved in the oxidative stress pathway. In an independent data set consisting primarily of African American and Asian American children, these three genes also showed a significant association with asthma status (P = .0008).

Black or African American↗

PubMed2005

Testing association and linkage using affected-sib-parent study designs.

We have developed a method for jointly testing linkage and association using data from affected sib pairs and their parents. We specify a conditional logistic regression model with two covariates, one that quantifies association (either direct association or indirect association via linkage disequilibrium), and a second that quantifies linkage. The latter covariate is computed based on expected identity-by-descend (ibd) sharing of marker alleles between siblings. In addition to a joint test of linkage and association, our general framework can be used to obtain a linkage test comparable to the mean test (Blackwelder and Elston [1985] Genet. Epidemiol. 2:85-97), and an association test comparable to the Family-Based Association Test (FBAT; Rabinowitz and Laird [2000] Hum. Hered. 50:211-223). We present simulation results demonstrating that our joint test can be more powerful than some standard tests of linkage or association. For example, with a relative risk of 2.7 per variant allele at a disease locus, the estimated power to detect a nearby marker with a modest level of LD was 58.1% by the mean test (linkage only), 69.8% by FBAT, and 82.5% by our joint test of linkage and association. Our model can also be used to obtain tests of linkage conditional on association and association conditional on linkage, which can be helpful in fine mapping.

Alleles↗

PubMed2005

Birth outcomes and prenatal exposure to ozone, carbon monoxide, and particulate matter: results from the Children's Health Study.

Exposures to ambient air pollutants have been associated with adverse birth outcomes. We investigated the effects of air pollutants on birth weight mediated by reduced fetal growth among term infants who were born in California during 1975-1987 and who participated in the Children's Health Study. Birth certificates provided maternal reproductive history and residence location at birth. Sociodemographic factors and maternal smoking during pregnancy were collected by questionnaire. Monthly average air pollutant levels were interpolated from monitors to the ZIP code of maternal residence at childbirth. Results from linear mixed-effects regression models showed that a 12-ppb increase in 24-hr ozone averaged over the entire pregnancy was associated with 47.2 g lower birth weight [95% confidence interval (CI), 27.4-67.0 g], and this association was most robust for exposures during the second and third trimesters. A 1.4-ppm difference in first-trimester carbon monoxide exposure was associated with 21.7 g lower birth weight (95% CI, 1.1-42.3 g) and 20% increased risk of intrauterine growth retardation (95% CI, 1.0-1.4). First-trimester CO and third-trimester O3 exposures were associated with 20% increased risk of intrauterine growth retardation. A 20-microg/m3 difference in levels of particulate matter < or = 10 microm in aerodynamic diameter (PM10) during the third trimester was associated with a 21.7-g lower birth weight (95% CI, 1.1-42.2 g), but this association was reduced and not significant after adjusting for O3. In summary, O3 exposure during the second and third trimesters and CO exposure during the first trimester were associated with reduced birth weight.

Adult↗

PubMed2004

Effects of ambient air pollutants on asthma medication use and wheezing among fourth-grade school children from 12 Southern California communities enrolled in The Children's Health Study.

To investigate the effects of 12 monthly average air pollution levels on monthly prevalence of respiratory morbidity, the authors examined retrospective questionnaire data on 2034 4th-grade children from 12 Southern California communities that were enrolled in The Children's Health Study. Wheezing during the spring and summer months was associated with community levels of airborne particulate matter with a diameter < or = 10 microm (PM10) (odds ratio (OR) = 2.91; 95% confidence interval (CI) = 1.46-5.80), but was not associated with community levels of ozone, nitrogen dioxide, PM2.5 (diameter < or = 2.5), nitric acid, or formic acid. Logistic regression was performed on data stratified into two seasonal groups, spring/summer and fall/winter. Among asthmatics, the monthly prevalence of asthma medication use was associated with monthly levels of ozone, nitric acid, and acetic acid (OR = 1.80 [95%CI = 1.19-2.70]; OR = 1.80 [95%CI = 1.23-2.65]; OR = 1.57 [95% CI = 1.11-2.21]; respectively). Asthma medication use was more prevalent among children who spent more time outdoors--with consequential exposure to ozone--than among children who spent more time indoors (OR = 3.07 [95%CI = 1.61-5.86]; OR = 1.31 [95%CI = 0.47-2.71]; respectively). The authors concluded that monthly variations in some ambient air pollutants were associated with monthly respiratory morbidity among school children.

Air Pollutants↗