AbstractBackgroundSerum 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.ResultsThe association betweenABOlocus and serum ALP levels was replicated (P = 2.50 × 10-21, 1.12 × 10-56and 2.82 × 10-27for SNP rs8176720, rs651007 and rs7025162 onABOlocus, 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 betweenABOrs651007 and overweight and obesity was observed (FDRfor 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.ConclusionsOur findings indicate thatABOlocus is a major determinant for serum ALP levels in Chinese Han population. Overweight and obesity modifies the effect ofABOlocus on serum ALP concentrations.