TY - JOUR
T1 - Genome-wide association study identifies novel loci associated with serum level of vitamin B12 in Chinese men
AU - Lin, Xiaoling
AU - Lu, Daru
AU - Gao, Yong
AU - Tao, Sha
AU - Yang, Xiaobo
AU - Feng, Junjie
AU - Tan, Aihua
AU - Zhang, Haiying
AU - Hu, Yanling
AU - Qin, Xue
AU - Kim, Seongtae
AU - Peng, Tao
AU - Li, Li
AU - Mo, Linjian
AU - Zhang, Shijun
AU - Trent, Jeffrey M.
AU - Mo, Zengnan
AU - Zheng, S. Lilly
AU - Xu, Jianfeng
AU - Sun, Jielin
PY - 2012/6/1
Y1 - 2012/6/1
N2 - Vitamin B12 (VitB12 or cobalamin) is an essential cofactor in several metabolic pathways. Clinically, VitB12 deficiency is associated with pernicious anemia, neurodegenerative disorder, cardiovascular disease and gastrointestinal disease. Although previous genome-wide association studies (GWAS) identified several genes, including FUT2, CUBN, TCN1 and MUT, that may influence VitB12 levels in European populations, common genetic determinants of VitB12 remain largely unknown, especially in Asian populations. Here we performed a GWAS in 1999 healthy Chinese men and replicated the top findings in an independent Chinese sample with 1496 subjects. We identified four novel genomic loci that were significantly associated with serum level of VitB12 at a genome-wide significance level of 5.00 × 10-8. These four loci were MS4A3 (11q12.1; rs2298585; P= 2.64 × 10-15), CLYBL (13q32; rs41281112; P= 9.23 × 10-10), FUT6 (19p13.3; rs3760776; P= 3.68 × 10-13) and 5q32 region (rs10515552; P= 3.94 × 10-8). In addition, we also confirmed the association with the serum level of VitB12 for the previously reported FUT2 gene and identified one novel non-synonymous single-nucleotide polymorphism in FUT2 gene in this Chinese population (19q13.33; rs1047781; P= 3.62 × 10-36). The new loci identified offer new insights into the biochemical pathways involved in determining the serum level of VitB12 and provide opportunities to better delineate the role of VitB12 in health and disease. © The Author 2012. Published by Oxford University Press. All rights reserved.
AB - Vitamin B12 (VitB12 or cobalamin) is an essential cofactor in several metabolic pathways. Clinically, VitB12 deficiency is associated with pernicious anemia, neurodegenerative disorder, cardiovascular disease and gastrointestinal disease. Although previous genome-wide association studies (GWAS) identified several genes, including FUT2, CUBN, TCN1 and MUT, that may influence VitB12 levels in European populations, common genetic determinants of VitB12 remain largely unknown, especially in Asian populations. Here we performed a GWAS in 1999 healthy Chinese men and replicated the top findings in an independent Chinese sample with 1496 subjects. We identified four novel genomic loci that were significantly associated with serum level of VitB12 at a genome-wide significance level of 5.00 × 10-8. These four loci were MS4A3 (11q12.1; rs2298585; P= 2.64 × 10-15), CLYBL (13q32; rs41281112; P= 9.23 × 10-10), FUT6 (19p13.3; rs3760776; P= 3.68 × 10-13) and 5q32 region (rs10515552; P= 3.94 × 10-8). In addition, we also confirmed the association with the serum level of VitB12 for the previously reported FUT2 gene and identified one novel non-synonymous single-nucleotide polymorphism in FUT2 gene in this Chinese population (19q13.33; rs1047781; P= 3.62 × 10-36). The new loci identified offer new insights into the biochemical pathways involved in determining the serum level of VitB12 and provide opportunities to better delineate the role of VitB12 in health and disease. © The Author 2012. Published by Oxford University Press. All rights reserved.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84861127422&origin=inward
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84861127422&origin=inward
U2 - 10.1093/hmg/dds062
DO - 10.1093/hmg/dds062
M3 - Article
C2 - 22367966
SN - 0964-6906
VL - 21
SP - 2610
EP - 2617
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 11
M1 - dds062
ER -
