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Metabolome-wide association study identified the association between a circulating polyunsaturated fatty acids variant rs174548 and lung cancer.
Wang, C, Qin, N, Zhu, M, Chen, M, Xie, K, Cheng, Y, Dai, J, Liu, J, Xia, Y, Ma, H, et al
Carcinogenesis. 2017;(11):1147-1154
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Abstract
Quantitative trait loci (QTLs) are widely used as instruments to infer causal risk factors of diseases based on the idea of mendelian randomization. Plasma metabolites can serve as risk factors of cancer, and the heritability of many circulating metabolites was high. We conducted a metabolome-wide association study (MWAS) to systematically investigate the effects of genetic variants on metabolites and lung cancer based on published genome-wide association study (GWASs) and metabolic-QTL (mQTL) study. Then we confirmed the results by subsequent genetic and metabolic validations and inferred the causal relationship between identified metabolites and lung cancer through genetic variant(s). We firstly identified six polyunsaturated fatty acids (PUFAs) represented by rs174548-linked haplotype were significantly associated with lung cancer risk in a Chinese GWAS (2311 cases and 3077 controls). Rs174548 was further confirmed to be associated with lung cancer in 13 821 Europeans and 18 471 Asians (ORmeta = 0.87, Pmeta = 1.76 × 10-15) and the effect was much stronger in females (Pinteraction = 6.00 × 10-4). We next validated rs174548-plasma PUFA association in 253 Chinese subjects (β = -0.57, P = 1.68 × 10-3). Rs174548 was also found associated with FADS1 (the major fatty acid desaturase of identified PUFAs) expression in liver tissues. Taken together, we found that rs174548 was associated with both PUFAs and lung cancer. Because rs174548 was the only mQTL variant of PUFAs reported by previous GWASs and explained a large proportion of heritability, we proposed that plasma PUFAs could be causally associated with lung cancer based on the idea of mendelian randomization. These findings provide a diet-related risk factor and may have important implications for prevention on lung cancer.
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CD40 C/T-1 polymorphism plays different roles in Graves' disease and Hashimoto's thyroiditis: a meta-analysis.
Li, M, Sun, H, Liu, S, Yu, J, Li, Q, Liu, P, Shen, H, Sun, D
Endocrine journal. 2012;(12):1041-50
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Abstract
CD40 plays a pathogenic role in various autoimmune diseases. However, studies investigating the association between CD40 C/T-1 polymorphism and autoimmune thyroid diseases risk have reported conflicting results and their relative population effect remains unclear; therefore, a meta-analysis was conducted. The data for this meta-analysis included 14 (4214 cases and 3851 controls) and 4 studies (623 cases and 774 controls) for the association of the CD40 C/T-1 polymorphism with Graves' disease (GD) and Hashimoto's thyroiditis (HT), respectively. Results suggested significant association for CD40 C/T-1 polymorphism (odds ratio 1.267 per C allele, p = 0.000) with GD but without HT. The individuals who carried the C/C or C/T genotype have significantly increased GD risk compared with those who carried T/T genotype (C/C vs. T/T: OR = 1.596, 95% CI, 1.256~2.028; C/T vs. T/T: OR = 1.210, 95% CI, 1.032~1.419; dominant model: OR = 1.366, 95% CI, 1.175~1.587; recessive model: OR = 1.322, 95% CI, 1.147~1.523), while no association was observed in HT. When stratified by ethnicity, the significant association between polymorphism and GD risk of Caucasians was found only in recessive models; but that of Asians was found in all models. In the subgroup analysis of study design, we found thyroid antibody status should be ascertained in controls and euthyroidism subjects with higher levels of thyroid antibody should be excluded from control and included into HT to avoid bias. Our meta-analysis showed that CD40 C/T-1 polymorphism plays different roles in GD and HT. Further studies will be needed to confirm our findings.