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Dastani, Z., Hivert, M. - F., Timpson, N., Perry, J. R. B., Yuan, X., Scott, R. A., et al. (2012). Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet, 8(3), e1002607.
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5x10(-8)-1.2x10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3x10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3x10(-3), n = 22,044), increased triglycerides (p = 2.6x10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8x10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4x10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5x10(-13), n = 96,748) and decreased BMI (p = 1.4x10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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Lu, X., Peloso, G. M., Liu, D. J., Wu, Y., Zhang, H., Zhou, W., et al. (2017). Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease (Vol. 49).
Abstract: Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.
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Tang, C. S., Zhang, H., Cheung, C. Y., Xu, M., Ho, J. C., Zhou, W., et al. (2015). Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese. Nature communications, 6, 10206.
Abstract: Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P
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Xiang, Y., Zhou, Z., Deng, C., & Leslie, R. D. (2013). Latent autoimmune diabetes in adults in Asians: similarities and differences between East and West. J Diabetes, 5(2), 118–126.
Abstract: Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with features of both type 1 and type 2 diabetes and in the middle of the diabetes spectrum. Scientists clash on the question of whether this type of diabetes is a unique diabetes subtype. Multicenter studies have been performed in different countries, including the Korea National Diabetes Program (KNDP) collaboratory group, the Ehime study in Japan, the Not Insulin-Requiring Autoimmune Diabetes (NIRAD) study in Italy, the Nord-Trondelag Health (HUNT) study in Norway, the UK Prospective Diabetes Study (UKPDS) in the UK, the Action LADA study in Europe and the LADA China study in China. These studies found universal immunogenetic effects associated with LADA, but with some ethnic differences. Herein we summarize those multicenter studies and compare the ethnic similarities and differences between East and West from epidemiological, clinical, immune, and genetic viewpoints.
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