Publication Date:
2017-03-28
Description:
Background— Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP. Methods and Results— We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P 〈5.0 x 10 –8 and 2.5 x 10 – 6 , respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P =5.03 x 10 – 8 , stage-2 P =8.64 x 10 – 3 , joint P =2.63 x 10 – 8 ) and mean arterial pressure (stage-1 P =3.59 x 10 – 9 , stage-2 P =2.35 x 10 – 2 , joint P =2.64 x 10 – 8 ). Three previously reported BP loci ( WBP1L , NT5C2 , and ATP2B1 ) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P =8.55 x 10 – 6 , stage-2 P =1.62 x 10 – 5 , joint P =3.28 x 10 – 9 ) and mean arterial pressure (stage-1 P =9.19 x 10 – 7 , stage-2 P =9.69 x 10 – 5 , joint P =2.15 x 10 – 9 ) phenotypes. Fourteen genes ( TMEM180 , ACTR1A , SUFU , ARL3 , SFXN2 , WBP1L , CYP17A1 , C10orf32 , C10orf32 - ASMT , AS3MT , CNNM2 , and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes ( P =1.27 x 10 – 4 and 3.30 x 10 – 4 , respectively). Conclusions— We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians.
Keywords:
Genetic, Association Studies, High Blood Pressure
Print ISSN:
1942-325X
Electronic ISSN:
1942-3268
Topics:
Medicine
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