Genome-wide association study on serum alkaline phosphatase levels in a Chinese population
- Equal contributors
1 MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, 430030 Wuhan, Hubei, China
2 State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, China
3 Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, 442008 Shiyan, Hubei, China
4 Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
5 Department of Epidemiology, School of Public Health and Management, Chongqing Medical University, 400016 Chongqing, China
BMC Genomics 2013, 14:684 doi:10.1186/1471-2164-14-684Published: 5 October 2013
Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated.
The association between ABO locus and serum ALP levels was replicated (P = 2.50 × 10-21, 1.12 × 10-56 and 2.82 × 10-27 for SNP rs8176720, rs651007 and rs7025162 on ABO locus, respectively). SNP rs651007 accounted for 2.15% of the total variance of serum ALP levels independently of the other 2 SNPs. When comparing our findings with previously published studies, ethnic differences were observed across populations. A significant interaction between ABO rs651007 and overweight and obesity was observed (FDR for interaction was 0.036); for individuals with GG genotype, those with normal weight and those who were overweight or obese have similar serum ALP concentrations; minor allele A of rs651007 remarkably reduced serum ALP levels, but this effect was attenuated in overweight and obese individuals.
Our findings indicate that ABO locus is a major determinant for serum ALP levels in Chinese Han population. Overweight and obesity modifies the effect of ABO locus on serum ALP concentrations.