Dataset Information

Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

ABSTRACT:

Background

The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.

Methods

We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.

Results

Two blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P<5×10^-8). Among them, a rare intergenic variant at novel locus, LOC100506274, was associated with lower systolic blood pressure in stage-1 (beta [SE]=-32.6 [6.0]; P=4.99×10^-8) but not stage-2 analysis (P=0.11). Furthermore, a novel common variant at the known INSR locus was suggestively associated with diastolic blood pressure in stage-1 (beta [SE]=-0.36 [0.07]; P=4.18×10^-7) and attained genome-wide significance in stage-2 (beta [SE]=-0.29 [0.03]; P=7.28×10^-23). Nineteen additional signals suggestively associated with blood pressure in meta-analysis of single and aggregate rare variant findings (P<1×10^-6 and P<1×10^-4, respectively).

Discussion

We report one promising but unconfirmed rare variant for blood pressure and, more importantly, contribute insights for future blood pressure sequencing studies. Our findings suggest promise of aggregate analyses to complement single variant analysis strategies and the need for larger, diverse samples, and family studies to enable robust rare variant identification.

SUBMITTER: Kelly TN

PROVIDER: S-EPMC9593435 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

Kelly Tanika N TN Sun Xiao X He Karen Y KY Brown Michael R MR Taliun Sarah A Gagliano SAG Hellwege Jacklyn N JN Irvin Marguerite R MR Mi Xuenan X Brody Jennifer A JA Franceschini Nora N Franceschini Nora N Guo Xiuqing X Hwang Shih-Jen SJ de Vries Paul S PS Gao Yan Y Moscati Arden A Nadkarni Girish N GN Yanek Lisa R LR Elfassy Tali T Smith Jennifer A JA Chung Ren-Hua RH Beitelshees Amber L AL Patki Amit A Aslibekyan Stella S Blobner Brandon M BM Peralta Juan M JM Assimes Themistocles L TL Palmas Walter R WR Liu Chunyu C Bress Adam P AP Huang Zhijie Z Becker Lewis C LC Hwa Chii-Min CM O'Connell Jeffrey R JR Carlson Jenna C JC Warren Helen R HR Das Sayantan S Giri Ayush A Martin Lisa W LW Craig Johnson W W Fox Ervin R ER Bottinger Erwin P EP Razavi Alexander C AC Vaidya Dhananjay D Chuang Lee-Ming LM Chang Yen-Pei C YC Naseri Take T Jain Deepti D Kang Hyun Min HM Hung Adriana M AM Srinivasasainagendra Vinodh V Snively Beverly M BM Gu Dongfeng D Montasser May E ME Reupena Muagututi'a Sefuiva MS Heavner Benjamin D BD LeFaive Jonathon J Hixson James E JE Rice Kenneth M KM Wang Fei Fei FF Nielsen Jonas B JB Huang Jianfeng J Khan Alyna T AT Zhou Wei W Nierenberg Jovia L JL Laurie Cathy C CC Armstrong Nicole D ND Shi Mengyao M Pan Yang Y Stilp Adrienne M AM Emery Leslie L Wong Quenna Q Hawley Nicola L NL Minster Ryan L RL Curran Joanne E JE Munroe Patricia B PB Weeks Daniel E DE North Kari E KE Tracy Russell P RP Kenny Eimear E EE Shimbo Daichi D Chakravarti Aravinda A Rich Stephen S SS Reiner Alex P AP Blangero John J Redline Susan S Mitchell Braxton D BD Rao Dabeeru C DC Ida Chen Yii-Der YD Kardia Sharon L R SLR Kaplan Robert C RC Mathias Rasika A RA He Jiang J Psaty Bruce M BM Fornage Myriam M Loos Ruth J F RJF Correa Adolfo A Boerwinkle Eric E Rotter Jerome I JI Kooperberg Charles C Edwards Todd L TL Abecasis Gonçalo R GR Zhu Xiaofeng X Levy Daniel D Arnett Donna K DK Morrison Alanna C AC

Hypertension (Dallas, Tex. : 1979) 20220602 8

<h4>Background</h4>The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.<h4>Methods</h4>We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=38 ...[more]

PMID: 35652341

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Dataset Information

Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

Background

Methods

Results

Discussion

Publications

Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

Similar Datasets

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