Ethnicity-specific associations with 5 pathways
Analysis using the semantic model for ethnicity-specific SNPs identified 5, 7, and 100 CEU-specific, JPT-specific, and YRI-specific biochemical pathways, respectively. In hemostasis (REACT:604), associated with cardiovascular diseases, plasminogen activator inhibitor-1 activity levels of Africans are lower compared to Caucasians. These negative effects can be seen already at a young age. If addressed in early life, it is possibly adjustable through behavior and optimal dietary changes [30]. Systemic lupus activity measure (SLAM; KEGG:05322) scores were higher in African-Americans (mean = 12.6) and Hispanics (11.0) than in Caucasians (8.5). It caused lack of health insurance, onset of abrupt disease, presence of anti-Ro (SSA) antibody, absence of HLA-DRB, high levels of helplessness, and abnormal illness behaviors. Caucasians lived under less crowded conditions, had less abnormal illness behaviors, and had more education. The results of the regression analyses were showed significant association between higher SLAM scores and higher helplessness, absence of HLA-DRB1*0301, and presence of HLA-DRB*0201 (p < 0.01) [31]. Prostate cancer (KEGG:05215) is a diagnosed male reproductive system cancer. Incidence of prostate cancer in African-American men is higher than in European men (1.6 times). Amundadottir et al. [32] identified that the chromosomal 8q24 region is most frequently gained in prostate cancers, and this gained region has been correlated with aggressive tumors [33]. Estimated population attributable risk is greater in Africans than in European populations. Hepatitis C virus (HCV; KEGG:05160) is a major cause of chronic liver disease in humans. Rates of HCV prevalence in sub-Saharan Africa are the highest in central Africa (3.0%) compared with the median (2.2%). Conjeevaram et al. [34] showed that African-Americans with chronic HCV have lower response to interferon-based antiviral therapy than Caucasian Americans [35]. Rheumatoid arthritis (RA; KEGG:05323) is an autoimmune disease and may affect many organs. The RA prevalence in urban South Africans is similar in Caucasians [36].
In the current study, the pathways shared between all populations were signal transduction (REACT:111102), olfactory transduction (KEGG:04740), and metabolic pathways (KEGG:01100). These pathways were common disease-pathway interactions in previous research. Although ethnicity-specific genes are identified in each population, it is generally observed that genes that are associated with a trait or disease can converge to the same pathway [37]. Those genes are also supposed to converge to common pathways shared between all populations. Therefore, a pathway-based approach allows us to systematically evaluate multiple polymorphic genes from different populations with respect to pathways as a biological unit [38]. Moreover, the pathway-based approach has more capability to detect rare genetic variants with a small effect that do not survive at the stringent significance level [39].
We identified ethnicity-specific SNPs from HapMap data and constructed a semantic network model for the HapMap SNP dataset. Functional studies were analyzed with genebased ethnicity-specific SNPs. Our semantic network model showed robust interactions between ethnic-specific SNPs and public data. However, this model is still in the early stage, and greater data connection and development of more flexible algorithms are required. We expect that our semantic network model is useful for ethnicity-specific SNPs, and our findings will provide prioritization of ethnicity-specific gene-based SNP candidates.