Abstract 11738: A Genome-wide Association Analysis Identifies PDE1A DNAJC10 Locus on Chromosome 2 Associated With Idiopathic Pulmonary Arterial Hypertension in the Japanese Population
Background: Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease with a mean survival period estimated to be around 3 years if not treated. Although many familial cases of IPAH exhibit an autosomal dominant mode of inheritance with the majority having mutations in BMPR2, the penetrance is low with an estimated lifetime risk of 20 %. To explain the low penetrance of IPAH associated with BMPR2 mutations, it was hypothesized that other genetic loci as well as environmental factors play roles.
Purpose: To identify genetic factors associated with IPAH with/ without BMPR2 mutation, we conducted a genome-wide association study (GWAS) followed by a validation study.
Methods and Results: We performed GWAS in the Japanese population comprising a total of 44 individuals with IPAH and 2,993 controls. The IPAH cases were identified at three major pulmonary hypertension centers in Japan. The controls consisted of 2,002 and 991 healthy Japanese individuals, which were collected at two different times by Japan PGx Data Science Consortium (JPDSC). At first, we conducted discovery GWAS to identify SNPs related to the disease, comparing 23 cases with IPAH (first set) and 2,002 controls at 1,347,690 SNPs, and identified 8 loci each of which had more than one SNP with P values under 10-5. We then attempted to validate the associations observed in the discovery phase using 21 patients (second set) and 991 controls who were independent of the samples used in the discovery GWAS. In the validation study, we examined the associations of 9 SNPs at 8 loci, and only 2 SNPs at one locus showed significant association. And finally, we identified a novel susceptibility locus PDE1A
Author Disclosures: M. Kimura: None. Y. Tamura: None. M. Takei: None. K. Kosaki: None. N. Tanabe: None. K. Tatsumi: None. T. Saji: None. T. Saji: None. T. Satoh: None. S. Kamitsuji: None. N. Kamatani: None. M. Sano: None. K. Fukuda: None.
- © 2015 by American Heart Association, Inc.