TY - JOUR
T1 - A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure
AU - The CHARGE Neurology Working Group
AU - The COGENT-Kidney Consortium
AU - The GIANT consortium
AU - Lifelines Cohort Study
AU - Sung, Yun J.
AU - Winkler, Thomas W.
AU - de las Fuentes, Lisa
AU - Bentley, Amy R.
AU - Brown, Michael R.
AU - Kraja, Aldi T.
AU - Schwander, Karen
AU - Ntalla, Ioanna
AU - Guo, Xiuqing
AU - Franceschini, Nora
AU - Lu, Yingchang
AU - Cheng, Ching Yu
AU - Sim, Xueling
AU - Vojinovic, Dina
AU - Marten, Jonathan
AU - Musani, Solomon K.
AU - Li, Changwei
AU - Feitosa, Mary F.
AU - Kilpeläinen, Tuomas O.
AU - Richard, Melissa A.
AU - Noordam, Raymond
AU - Aslibekyan, Stella
AU - Aschard, Hugues
AU - Bartz, Traci M.
AU - Dorajoo, Rajkumar
AU - Liu, Yongmei
AU - Manning, Alisa K.
AU - Rankinen, Tuomo
AU - Smith, Albert Vernon
AU - Tajuddin, Salman M.
AU - Tayo, Bamidele O.
AU - Warren, Helen R.
AU - Zhao, Wei
AU - Zhou, Yanhua
AU - Matoba, Nana
AU - Sofer, Tamar
AU - Alver, Maris
AU - Amini, Marzyeh
AU - Boissel, Mathilde
AU - Chai, Jin Fang
AU - Chen, Xu
AU - Divers, Jasmin
AU - Gandin, Ilaria
AU - Gao, Chuan
AU - Giulianini, Franco
AU - Goel, Anuj
AU - Harris, Sarah E.
AU - Hartwig, Fernando Pires
AU - Horimoto, Andrea R.V.R.
AU - Meitinger, Thomas
N1 - Publisher Copyright:
© 2018 American Society of Human Genetics
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10−8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10−8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).
AB - Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10−8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10−8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).
KW - GWAS
KW - GxE interactions
KW - blood pressure
KW - lifestyle
KW - multi-ancestry
KW - smoking
UR - https://www.scopus.com/pages/publications/85042027943
U2 - 10.1016/j.ajhg.2018.01.015
DO - 10.1016/j.ajhg.2018.01.015
M3 - Article
C2 - 29455858
AN - SCOPUS:85042027943
SN - 0002-9297
VL - 102
SP - 375
EP - 400
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -