Kayama T.,Yamagata University |
Fukao A.,Advanced Molecular Epidemiology Research Institute AMERI |
Kubota I.,Respiratory and Cardiovascular Diseases Research Center |
Kato T.,Metabolic and Degenerative Diseases Research Center |
And 55 more authors.
PLoS ONE | Year: 2014
For forty-three clinical test values presumably associated to common complex human diseases, we carried out a genomewide association study using 600K SNPs in a general Japanese population of 1,639 individuals (1,252 after quality control procedures) drawn from a regional cohort, followed by a replication study for statistically significant SNPs (p = 1.95×10-9- 8.34×10-39) using an independent population of 1,671 from another cohort. In this single two-stage study, we newly found strong and robust associations of common variants at the ABO histo-blood glycosyltransferase locus in 9q32 with the plasma levels of pancreatic lipase (P-LIP), in addition to successful confirmation of the known ABO association of angiotensin converting enzyme (ACE) independent of the ACE1 gene in 17q23.2 with the ACE level. Our results are compatible with the previously reported association between the ABO gene and pancreatic cancer, and show that the effect of these common variants at the ABO locus on the P-LIP and ACE levels is largely opposing and pleiotropic. © 2014 Tamiya et al.