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1.  Genetic Variants on 15q25.1, Smoking, and Lung Cancer: An Assessment of Mediation and Interaction 
American Journal of Epidemiology  2012;175(10):1013-1020.
Genome-wide association studies have identified variants on chromosome 15q25.1 that increase the risks of both lung cancer and nicotine dependence and associated smoking behavior. However, there remains debate as to whether the association with lung cancer is direct or is mediated by pathways related to smoking behavior. Here, the authors apply a novel method for mediation analysis, allowing for gene-environment interaction, to a lung cancer case-control study (1992–2004) conducted at Massachusetts General Hospital using 2 single nucleotide polymorphisms, rs8034191 and rs1051730, on 15q25.1. The results are validated using data from 3 other lung cancer studies. Tests for additive interaction (P = 2 × 10−10 and P = 1 × 10−9) and multiplicative interaction (P = 0.01 and P = 0.01) were significant. Pooled analyses yielded a direct-effect odds ratio of 1.26 (95% confidence interval (CI): 1.19, 1.33; P = 2 × 10−15) for rs8034191 and an indirect-effect odds ratio of 1.01 (95% CI: 1.00, 1.01; P = 0.09); the proportion of increased risk mediated by smoking was 3.2%. For rs1051730, direct- and indirect-effect odds ratios were 1.26 (95% CI: 1.19, 1.33; P = 1 × 10−15) and 1.00 (95% CI: 0.99, 1.01; P = 0.22), respectively, with a proportion mediated of 2.3%. Adjustment for measurement error in smoking behavior allowing up to 75% measurement error increased the proportions mediated to 12.5% and 9.2%, respectively. These analyses indicate that the association of the variants with lung cancer operates primarily through other pathways.
doi:10.1093/aje/kwr467
PMCID: PMC3353137  PMID: 22306564
gene-environment interaction; lung neoplasms; mediation; pathway analysis; smoking
2.  Psychosocial Risk and Correlates of Early Menarche in Mexican-American Girls 
American Journal of Epidemiology  2011;173(10):1203-1210.
Mexican-American girls have one of the fastest rates of decline in age at menarche. To date, no study has addressed the role of psychosocial factors on age at menarche in this population. Using data from a longitudinal cohort of Mexican-American girls from the Houston, Texas, metropolitan area recruited in 2005, the authors investigated associations between family life and socioeconomic environment and age at menarche in 523 girls. After adjusting for maternal age at menarche, daughter's age, and body mass index at baseline, perception of family life environment as conflict-prone was significantly associated with an earlier age at menarche (< 11 years). Additionally, there was a 2-fold higher risk (odds ratio = 2.22, 95% confidence interval: 1.12, 4.40) of early menarche among daughters of mothers who were single parents compared with those who were not. Furthermore, girls who matured early had a 2.5-fold increased risk (odds ratio = 2.69, 95% confidence interval: 1.04, 6.96) of experimenting with cigarettes compared with those who had an average-to-late age at menarche (≥ 11 years). This study provides important information regarding the role of family life environment and single parenting on age at menarche in Mexican Americans. Awareness of the impact of the family life environment and fathers’ absence during the early years should be emphasized when addressing early age at menarche across cultures.
doi:10.1093/aje/kwq498
PMCID: PMC3121322  PMID: 21454827
family cohesion; family conflict; menarche; Mexican Americans; single parenting; smoking; social support
3.  The PhenX Toolkit: Get the Most From Your Measures 
American Journal of Epidemiology  2011;174(3):253-260.
The potential for genome-wide association studies to relate phenotypes to specific genetic variation is greatly increased when data can be combined or compared across multiple studies. To facilitate replication and validation across studies, RTI International (Research Triangle Park, North Carolina) and the National Human Genome Research Institute (Bethesda, Maryland) are collaborating on the consensus measures for Phenotypes and eXposures (PhenX) project. The goal of PhenX is to identify 15 high-priority, well-established, and broadly applicable measures for each of 21 research domains. PhenX measures are selected by working groups of domain experts using a consensus process that includes input from the scientific community. The selected measures are then made freely available to the scientific community via the PhenX Toolkit. Thus, the PhenX Toolkit provides the research community with a core set of high-quality, well-established, low-burden measures intended for use in large-scale genomic studies. PhenX measures will have the most impact when included at the experimental design stage. The PhenX Toolkit also includes links to standards and resources in an effort to facilitate data harmonization to legacy data. Broad acceptance and use of PhenX measures will promote cross-study comparisons to increase statistical power for identifying and replicating variants associated with complex diseases and with gene-gene and gene-environment interactions.
doi:10.1093/aje/kwr193
PMCID: PMC3141081  PMID: 21749974
environmental exposure; epidemiologic methods; genetic research; genetics; genome-wide association study; meta-analysis as topic; phenotype; research design

Results 1-3 (3)