Browsing by Author "Chuang, Lee-Ming"

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A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2
(2014-02-15)
Wu, Ying
;
Gao, He
;
Li, Huaixing
;
Tabara, Yasuharu
;
Nakatochi, Masahiro
Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P 3.0 10(14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P 1.2 10(7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P 6.8 10(165)), ADIPOQ (P 1.8 10(22)), PEPD (P 3.6 10(12)), CMIP (P 2.1 10(10)), ZNF664 (P 2.3 10(7)) and GPR109A (P 7.4 10(6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (P-initial 0.020; P-conditional 7.0 10(7)). We further confirmed the independence of two pairs of closely located loci (2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P 3.3 10(4)), high density lipoprotein cholesterol (HDL-C, P 4.9 10(4)) and body mass index (BMI)-adjusted waisthip ratio (P 9.8 10(3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.
Simultaneous estimation of the locations and effects of multiple disease loci in case-control studies
(2015-04-01)
Chien, Li-Chu
;
Chiu, Yen-Feng
;
Liang, Kung-Yee
;
Chuang, Lee-Ming
;
統計學研究所
The genetic basis of complex diseases often involves multiple causative loci. Under such a disease etiology, assuming one disease locus in linkage disequilibrium mapping is likely to induce bias and lead to efficiency loss in disease locus estimation. An approach is needed for simultaneously localizing multiple functional loci within the same region. However, due to the increasing number of parameters accompanying disease loci, these estimates can be computationally infeasible. To circumvent this problem, we propose to estimate the main and two-adjacent-locus joint effects and a nuisance parameter at the disease loci separately through a linear approximation. Estimates of the genetic effects are entered into a generalized estimating equation to estimate disease loci, and the procedure is conducted iteratively until convergence. The proposed method provides estimates and confidence intervals (CIs) for the disease loci, the genetic main effects, and the joint effects of two adjacent disease loci, with the CIs for the disease loci providing useful regions for further fine-mapping. We apply the proposed approach to a data example of case-control studies. Results of the simulations and data example suggest that the developed method performs well in terms of bias, variance, and coverage probability under scenarios with up to three disease loci.