People over the age of seventy are at greatest risk of fall-related mortality (Ivers et al., 1998). As the second leading cause of blindness in the United States (Resnikoff et al., 2004), glaucoma is a driving force behind visual impairment. Glaucoma can be distinguished from other conditions of optic neuropathy via the presentation of optic nerve tissue (pink versus loss of color) and optic nerve cup formation (present versus not present) (Kwon et al., 2009).
Multiple populations have been used in research into the heredity of diabetes (WONG et al., 2006), (Leslie and Pyke, 1982). SiMES genotyping methods followed those of the SP2 cohort as previously described (Sim et al., 2011). They identified a positive interaction effect between lutein/zeaxanthin intake and genetic risk (Wang et al., 2013).
As the second leading cause of blindness in the United States (Resnikoff et al., 2004), glaucoma is a leading cause of visual impairment. As part of the PAGE I study (Matise et al., 2011a), as the Epidemiological Architecture for Genes Linked to Environment (EAGLE) study, we accessed ~15,000 DNA samples from non-European ancestry individuals in BioVU (EAGLE BioVU) to perform genetic association studies in diverse populations. The EAGLE study, as part of the PAGE I study (Matise et al., 2011a), accesses clinical and epidemiologic collections with racially/ethnically diverse populations.
The type 2 diabetes algorithm was developed as part of the Electronic Medical Records and Genomics (eMERGE) network (Kho et al., 2012). In contrast, fifty percent of African American glaucoma patients go undiagnosed in the United States (Ladapo et al., 2012). As IOP rises, the mechanical stress is greater in axially longer eyes (Kuzin et al., 2010).
The overall number of women affected by POAG exceeds that of men in the US (Vajaranant et al., 2012b). The myocilin (MYOC) gene, which was originally named the Trabecular Reticulum-Inducible Glucocorticoid Response (TIGR) Gene, was discovered in 1997 (Polansky et al., 1997). It requires glycolysis to meet these needs instead of the more common oxidative phosphorylation mode of ATP production (Antonetti et al., 2006).
Multiple heritability studies of diabetes have been performed in different populations (WONG et al., 2006), (Leslie and Pyke, 1982). Mutations in TJP2 were found to cause familial hypercholenemia in the Lancaster County Old Order Amish (Carlton et al., 2003). In the Netherlands, women used an average of seventeen personal care products per day while men used six (Biesterbos et al., 2013).
These chemicals are frequently found in urine samples from adults and children in the United States (Calafat et al., 2008).
Appendix
Each study site performed association tests using logistic regression assuming an additive genetic model. Results are shown for nominally significant tests (p<0.05) adjusted for age, sex, body mass index, smoking status (ever/never) and HDL cholesterol (mg/dL) regardless of fasting status (Model 3). Direction of effect is given for ARIC, CHS and EAGLE for EA, AA and MA if data are available.
Supplementary Figure 1: Synthesis display plot of nominally significant (p < 0.05) meta-analysis association results for model 3 adjusted for site of ascertainment, age, sex, BMI, smoking status, and HDL cholesterol regardless of fasting status. Included are the results of SNPs that were nominally significant in model 2 but not in model 3 to facilitate comparison. The two models differed in HDL status (irrespective of fasting vs. fasting) and use of Asian cohort (SiMES only vs. SiMES/SP2).
Supplementary Table 4: Mitochondrial genetic association results for model adjusted for age, sex, BMI and smoking status.
Appendix
Supplementary Figure 2: Flowchart of the decision tree involved in the determination of type 2 diabetes in African Americans by EAGLE BioVU (n=1672). Supplementary Table 7: Study population characteristics of all POAG cases and controls among African Americans in EAGLE BioVU. Age at POAG diagnosis was determined by the date the POAG ICD was first mentioned in the records.
Age at last clinic visit (LCV) was taken as the date of the last CPT mentioned in the records of controls. A person was classified as hypertensive if he/she met one of three criteria: systolic blood pressure > 140 mm/Hg, diastolic blood pressure > 90 mm/Hg, or on hypertension medication, all within a two-year window of becoming diagnosed with POAG in cases and a two-year period of their LCV date for controls. Blood pressure (systolic and diastolic), lipids (total cholesterol, high-density cholesterol, low-density cholesterol, and triglycerides), and body mass index (height and weight) were calculated from laboratories or measurements within two years of POAG diagnosis or LCV.
Appendix
Supplementary Table 9: Twenty most significant results for genetic association analysis of CDKN2B-AS1 region in African American cases (n=138) and controls (n=1,376). Logistic regression assuming an additive genetic model was performed for adjusted for age, sex, and PC. Supplementary Figure 4: Quantile-quantile plots drawn in STATA 12.0 of p-values in the CDKN2B-AS1 association analyzes of logistic regression model adjusted by age, sex, and first three PC.
Supplementary Figure 3: Quantile-quantile plots drawn in STATA 12.0 of p-values in the CDKN2B-AS1 association analyzes of logistic regression model adjusted by age, gender and median diastolic blood pressure. Supplementary Figure 6: Quantile-quantile plots drawn in STATA 12.0 of p-values in the CDKN2B-AS1 association analyzes of logistic regression model adjusted by age, sex, first 3 PC, and Supplementary Figure 5: Power calculations determined in Quanto for the EAGLE BioVU African-American POAG cohort accepting 135 cases with a case: control ratio of 1:3, log-addition model, and a 2-tailed t-test. The color-coded lines represent the different allele frequencies tested for in these power calculations.
Supplementary Table 10: One hundred most significant results for genetic association analysis of Metabochip POAG cases and African Americans (n=138) and controls (n=1,376). Supplementary Table 11: One hundred most significant results for genetic association analysis of POAG cases with Metabochip and African Americans (n=138) and controls (n=1,376). Logistic regression assuming an additive genetic model was performed to adjust for age, sex, PC and mean diastolic blood pressure.
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