Meta-Analysis

. 2022 Aug;79(8):1656-1667.

doi: 10.1161/HYPERTENSIONAHA.122.19324. Epub 2022 Jun 2.

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

Tanika N Kelly^#^{1

2}, Xiao Sun^#¹, Karen Y He^#³, Michael R Brown^#⁴, Sarah A Gagliano Taliun^#⁵, Jacklyn N Hellwege^#^{6

7}, Marguerite R Irvin^#⁸, Xuenan Mi^#¹, Jennifer A Brody^#⁹, Nora Franceschini¹⁰, Xiuqing Guo¹¹, Shih-Jen Hwang¹², Paul S de Vries⁴, Yan Gao¹³, Arden Moscati¹⁴, Girish N Nadkarni^{14

15}, Lisa R Yanek¹⁶, Tali Elfassy¹⁷, Jennifer A Smith¹⁸, Ren-Hua Chung¹⁹, Amber L Beitelshees²⁰, Amit Patki²¹, Stella Aslibekyan⁸, Brandon M Blobner^{22

23}, Juan M Peralta²⁴, Themistocles L Assimes^{25

26}, Walter R Palmas²⁷, Chunyu Liu²⁸, Adam P Bress²⁹, Zhijie Huang¹, Lewis C Becker³⁰, Chii-Min Hwa³¹, Jeffrey R O'Connell²⁰, Jenna C Carlson³², Helen R Warren^{33

34}, Sayantan Das⁵, Ayush Giri^{7

35}, Lisa W Martin³⁶, W Craig Johnson³⁷, Ervin R Fox³⁸, Erwin P Bottinger³⁹, Alexander C Razavi¹, Dhananjay Vaidya¹⁶, Lee-Ming Chuang⁴⁰, Yen-Pei C Chang²⁰, Take Naseri⁴¹, Deepti Jain³⁷, Hyun Min Kang⁵, Adriana M Hung^{42

7}, Vinodh Srinivasasainagendra²¹, Beverly M Snively⁴³, Dongfeng Gu⁴⁴, May E Montasser²⁰, Muagututi'a Sefuiva Reupena⁴⁵, Benjamin D Heavner³⁷, Jonathon LeFaive⁵, James E Hixson⁴, Kenneth M Rice³⁷, Fei Fei Wang³⁷, Jonas B Nielsen^{46

47}, Jianfeng Huang^{2

44}, Alyna T Khan³⁷, Wei Zhou⁴⁸, Jovia L Nierenberg¹, Cathy C Laurie³⁷, Nicole D Armstrong⁸, Mengyao Shi¹, Yang Pan¹, Adrienne M Stilp³⁷, Leslie Emery³⁷, Quenna Wong³⁷, Nicola L Hawley⁴⁹, Ryan L Minster²³, Joanne E Curran²⁴, Patricia B Munroe^{33

34}, Daniel E Weeks^{23

50}, Kari E North⁹, Russell P Tracy⁵¹, Eimear E Kenny^{13

52}, Daichi Shimbo⁵³, Aravinda Chakravarti⁵⁴, Stephen S Rich⁵⁵, Alex P Reiner⁵⁶, John Blangero²⁴, Susan Redline⁵⁷, Braxton D Mitchell^{20

58}, Dabeeru C Rao⁵⁹, Yii-Der Ida Chen¹¹, Sharon L R Kardia¹⁸, Robert C Kaplan⁶⁰, Rasika A Mathias⁶¹, Jiang He¹, Bruce M Psaty^{1

62}, Myriam Fornage^{63

64}, Ruth J F Loos^{11

65}, Adolfo Correa⁶⁶, Eric Boerwinkle^{4

67}, Jerome I Rotter¹¹, Charles Kooperberg⁵⁶, Todd L Edwards^#^{68

7}, Gonçalo R Abecasis^#⁵, Xiaofeng Zhu^#³, Daniel Levy^#¹¹, Donna K Arnett^#⁶⁹, Alanna C Morrison^#⁴; Samoan Obesity, Lifestyle, and Genetic Adaptations Study (OLaGA) Group,‡ NHLBI Trans-Omics for Precision Medicine TOPMed) Consortium

Affiliations

¹ Department of Epidemiology (T.N.K., X.S., X.M., Z.H., A.C.R., J.L.N., M.S., Y.P., J.H.), Tulane University, New Orleans, LA.
² Translational Sciences Institute (T.N.K., J.H.), Tulane University, New Orleans, LA.
³ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH (K.Y.H., X.Z.).
⁴ Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health (M.R.B., P.D.d.V., J.E.H., E.B., A.C.M.), The University of Texas Health Science Center at Houston' Houston' TX.
⁵ Department of Biostatistics (S.A.G.T., S.D., H.M.K., J.L., G.R.A.), University of Michigan, Ann Arbor' MI.
⁶ Division of Genetic Medicine, Department of Medicine (J.N.H.), Vanderbilt University Medical Center, Nashville, TN.
⁷ Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville' TN (J.N.H., A.G., A.M.H., T.L.E.).
⁸ Department of Epidemiology (M.R.I., S.A., N.D.A.), University of Alabama at Birmingham' AL.
⁹ Cardiovascular Health Research Unit, Department of Medicine (J.A.B., K.E.N.), University of Washington, Seattle' WA.
¹⁰ Department of Epidemiology, University of North Carolina, Chapel Hill (N.F.).
¹¹ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance' CA (X.G., Y.-D.I.C., J.I.R., D.L.).
¹² National Heart, Lung and Blood Institute, Population Sciences Branch, National Institutes of Health, Framingham, MA (S.-J.H.).
¹³ Department of Physiology and Biophysics (Y.G., E.E.K., R.J.F.L.), University of Mississippi Medical Center, Jackson' MS.
¹⁴ The Charles Bronfman Institute for Personalized Medicine (A.M., G.N.N.), The Icahn School of Medicine at Mount Sinai, New York, NY.
¹⁵ Department of Medicine (G.N.N.), The Icahn School of Medicine at Mount Sinai, New York, NY.
¹⁶ Division of General Internal Medicine, Department of Medicine (L.R.Y., D.V.), Johns Hopkins University School of Medicine, Baltimore, MD.
¹⁷ Division of Epidemiology, Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami' FL (T.E.).
¹⁸ Department of Epidemiology (J.A.S., S.L.R.K.), University of Michigan, Ann Arbor' MI.
¹⁹ Institute of Population Sciences, National Health Research Institutes, Taiwan (R.-H.C.).
²⁰ Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore' MD (A.L.B., J.R.O., Y.-P.C.C., M.E.M., B.D.M.).
²¹ Department of Biostatistics (A.P., V.S.), University of Alabama at Birmingham' AL.
²² Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services (B.M.P.), University of Washington, Seattle' WA.
²³ Department of Human Genetics (B.M.B., R.L.M., D.E.W.), University of Pittsburgh, PA.
²⁴ Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville' TX (J.M.P., J.E.C., J.B.).
²⁵ Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford' CA (T.L.A.).
²⁶ Division of Cardiology Medicine, Palo Alto VA HealthCare System, Palo Alto' CA (T.L.A.).
²⁷ Division of General Medicine, Department of Medicine, Columbia University, New York, NY (W.R.P.).
²⁸ Department of Biostatistics, Boston University, Boston' MA (C.L.).
²⁹ Division of Health System Innovation and Research, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City' UT (A.P.B.).
³⁰ Division of Cardiology, Department of Medicine (L.C.B.), Johns Hopkins University School of Medicine, Baltimore, MD.
³¹ Taichung Veterans General Hospital, Taichung, Taiwan (C.-M.H.).
³² Department of Biostatistics, Graduate School of Public Health (J.C.C.), University of Pittsburgh, PA.
³³ Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry (H.R.W., P.B.M.), Queen Mary University of London, United Kingdom.
³⁴ National Institute for Health Research Barts Cardiovascular Biomedical Research Centre (H.R.W., P.B.M.), Queen Mary University of London, United Kingdom.
³⁵ Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN (A.G.).
³⁶ Division of Cardiology, Department of Medicine, George Washington University, Washington, DC (L.W.M.).
³⁷ Department of Biostatistics, School of Public Health (W.C.J., D.J., B.D.H., K.M.R., F.F.E., A.T.K., C.C.L., A.M.S., L.E., Q.W.), University of Washington, Seattle' WA.
³⁸ Division of Cardiology, Department of Medicine (E.R.F.), University of Mississippi Medical Center, Jackson' MS.
³⁹ Hasso Plattner Institute for Digital Health at Mount Sinai (E.P.B.), The Icahn School of Medicine at Mount Sinai, New York, NY.
⁴⁰ Department of Internal Medicine, National Taiwan University Hospital, Taipei' Taiwan (L.-M.C.).
⁴¹ Ministry of Health, Government of Samoa, Apia' Samoa (T.N.).
⁴² Division of Nephrology and Hypertension, Department of Medicine (A.M.H.), Vanderbilt University Medical Center, Nashville, TN.
⁴³ Division of Public Health Sciences, Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC (B.M.S.).
⁴⁴ Department of Epidemiology and Key Laboratory of Cardiovascular Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (D.G., J.H.).
⁴⁵ Lutia i Puava ae Mapu i Fagalele, Apia, Samoa (M.S.R.).
⁴⁶ Department of Internal Medicine: Cardiology (J.B.N.), University of Michigan, Ann Arbor' MI.
⁴⁷ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (J.B.N.).
⁴⁸ Department of Computational Medicine and Bioinformatics (W.Z.), University of Michigan, Ann Arbor' MI.
⁴⁹ Department of Chronic Disease Epidemiology, Yale University, New Haven, CT (N.L.H.).
⁵⁰ Department of Biostatistics (D.E.W.), University of Pittsburgh, PA.
⁵¹ Department of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington' VT (R.P.T.).
⁵² Department of Genetics and Genomics (E.E.K.), The Icahn School of Medicine at Mount Sinai, New York, NY.
⁵³ Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY (D.S.).
⁵⁴ Department of Medicine (A.C.), University of Mississippi Medical Center, Jackson' MS.
⁵⁵ Center for Public Health, University of Virginia, Charlottesville' VA (S.S.R.).
⁵⁶ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (A.P.R., C.K.).
⁵⁷ Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA (S.R.).
⁵⁸ Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore' MD (B.D.M.).
⁵⁹ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO (D.C.R.).
⁶⁰ Division of Social Medicine, Albert Einstein College of Medicine, Bronx, NY (R.C.K.).
⁶¹ Division of Allergy & Clinical Immunology, Department of Medicine (R.A.M.), Johns Hopkins University School of Medicine, Baltimore, MD.
⁶² Kaiser Permanente Washington Health Research Institute, Seattle' WA (B.M.P.).
⁶³ Brown Foundation Institute of Molecular Medicine (M.F.), The University of Texas Health Science Center at Houston' Houston' TX.
⁶⁴ Human Genetics Center (M.F.), The University of Texas Health Science Center at Houston' Houston' TX.
⁶⁵ The Mindich Child Health and Development Institute (R.J.F.L.), The Icahn School of Medicine at Mount Sinai, New York, NY.
⁶⁶ Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY (A.C.).
⁶⁷ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (E.B.).
⁶⁸ Division of Epidemiology, Department of Medicine (T.L.E.), Vanderbilt University Medical Center, Nashville, TN.
⁶⁹ College of Public Health, University of Kentucky, Lexington, KY (D.K.A.).

^# Contributed equally.

PMID: 35652341
PMCID: PMC9593435
DOI: 10.1161/HYPERTENSIONAHA.122.19324

Meta-Analysis

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

Tanika N Kelly et al. Hypertension. 2022 Aug.

. 2022 Aug;79(8):1656-1667.

doi: 10.1161/HYPERTENSIONAHA.122.19324. Epub 2022 Jun 2.

Authors

Affiliations

¹ Department of Epidemiology (T.N.K., X.S., X.M., Z.H., A.C.R., J.L.N., M.S., Y.P., J.H.), Tulane University, New Orleans, LA.
² Translational Sciences Institute (T.N.K., J.H.), Tulane University, New Orleans, LA.
³ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH (K.Y.H., X.Z.).
⁴ Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health (M.R.B., P.D.d.V., J.E.H., E.B., A.C.M.), The University of Texas Health Science Center at Houston' Houston' TX.
⁵ Department of Biostatistics (S.A.G.T., S.D., H.M.K., J.L., G.R.A.), University of Michigan, Ann Arbor' MI.
⁶ Division of Genetic Medicine, Department of Medicine (J.N.H.), Vanderbilt University Medical Center, Nashville, TN.
⁷ Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626)/Vanderbilt University, Nashville' TN (J.N.H., A.G., A.M.H., T.L.E.).
⁸ Department of Epidemiology (M.R.I., S.A., N.D.A.), University of Alabama at Birmingham' AL.
⁹ Cardiovascular Health Research Unit, Department of Medicine (J.A.B., K.E.N.), University of Washington, Seattle' WA.
¹⁰ Department of Epidemiology, University of North Carolina, Chapel Hill (N.F.).
¹¹ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance' CA (X.G., Y.-D.I.C., J.I.R., D.L.).
¹² National Heart, Lung and Blood Institute, Population Sciences Branch, National Institutes of Health, Framingham, MA (S.-J.H.).
¹³ Department of Physiology and Biophysics (Y.G., E.E.K., R.J.F.L.), University of Mississippi Medical Center, Jackson' MS.
¹⁴ The Charles Bronfman Institute for Personalized Medicine (A.M., G.N.N.), The Icahn School of Medicine at Mount Sinai, New York, NY.
¹⁵ Department of Medicine (G.N.N.), The Icahn School of Medicine at Mount Sinai, New York, NY.
¹⁶ Division of General Internal Medicine, Department of Medicine (L.R.Y., D.V.), Johns Hopkins University School of Medicine, Baltimore, MD.
¹⁷ Division of Epidemiology, Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami' FL (T.E.).
¹⁸ Department of Epidemiology (J.A.S., S.L.R.K.), University of Michigan, Ann Arbor' MI.
¹⁹ Institute of Population Sciences, National Health Research Institutes, Taiwan (R.-H.C.).
²⁰ Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore' MD (A.L.B., J.R.O., Y.-P.C.C., M.E.M., B.D.M.).
²¹ Department of Biostatistics (A.P., V.S.), University of Alabama at Birmingham' AL.
²² Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services (B.M.P.), University of Washington, Seattle' WA.
²³ Department of Human Genetics (B.M.B., R.L.M., D.E.W.), University of Pittsburgh, PA.
²⁴ Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville' TX (J.M.P., J.E.C., J.B.).
²⁵ Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford' CA (T.L.A.).
²⁶ Division of Cardiology Medicine, Palo Alto VA HealthCare System, Palo Alto' CA (T.L.A.).
²⁷ Division of General Medicine, Department of Medicine, Columbia University, New York, NY (W.R.P.).
²⁸ Department of Biostatistics, Boston University, Boston' MA (C.L.).
²⁹ Division of Health System Innovation and Research, Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City' UT (A.P.B.).
³⁰ Division of Cardiology, Department of Medicine (L.C.B.), Johns Hopkins University School of Medicine, Baltimore, MD.
³¹ Taichung Veterans General Hospital, Taichung, Taiwan (C.-M.H.).
³² Department of Biostatistics, Graduate School of Public Health (J.C.C.), University of Pittsburgh, PA.
³³ Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry (H.R.W., P.B.M.), Queen Mary University of London, United Kingdom.
³⁴ National Institute for Health Research Barts Cardiovascular Biomedical Research Centre (H.R.W., P.B.M.), Queen Mary University of London, United Kingdom.
³⁵ Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN (A.G.).
³⁶ Division of Cardiology, Department of Medicine, George Washington University, Washington, DC (L.W.M.).
³⁷ Department of Biostatistics, School of Public Health (W.C.J., D.J., B.D.H., K.M.R., F.F.E., A.T.K., C.C.L., A.M.S., L.E., Q.W.), University of Washington, Seattle' WA.
³⁸ Division of Cardiology, Department of Medicine (E.R.F.), University of Mississippi Medical Center, Jackson' MS.
³⁹ Hasso Plattner Institute for Digital Health at Mount Sinai (E.P.B.), The Icahn School of Medicine at Mount Sinai, New York, NY.
⁴⁰ Department of Internal Medicine, National Taiwan University Hospital, Taipei' Taiwan (L.-M.C.).
⁴¹ Ministry of Health, Government of Samoa, Apia' Samoa (T.N.).
⁴² Division of Nephrology and Hypertension, Department of Medicine (A.M.H.), Vanderbilt University Medical Center, Nashville, TN.
⁴³ Division of Public Health Sciences, Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC (B.M.S.).
⁴⁴ Department of Epidemiology and Key Laboratory of Cardiovascular Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (D.G., J.H.).
⁴⁵ Lutia i Puava ae Mapu i Fagalele, Apia, Samoa (M.S.R.).
⁴⁶ Department of Internal Medicine: Cardiology (J.B.N.), University of Michigan, Ann Arbor' MI.
⁴⁷ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (J.B.N.).
⁴⁸ Department of Computational Medicine and Bioinformatics (W.Z.), University of Michigan, Ann Arbor' MI.
⁴⁹ Department of Chronic Disease Epidemiology, Yale University, New Haven, CT (N.L.H.).
⁵⁰ Department of Biostatistics (D.E.W.), University of Pittsburgh, PA.
⁵¹ Department of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington' VT (R.P.T.).
⁵² Department of Genetics and Genomics (E.E.K.), The Icahn School of Medicine at Mount Sinai, New York, NY.
⁵³ Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY (D.S.).
⁵⁴ Department of Medicine (A.C.), University of Mississippi Medical Center, Jackson' MS.
⁵⁵ Center for Public Health, University of Virginia, Charlottesville' VA (S.S.R.).
⁵⁶ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (A.P.R., C.K.).
⁵⁷ Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA (S.R.).
⁵⁸ Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore' MD (B.D.M.).
⁵⁹ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO (D.C.R.).
⁶⁰ Division of Social Medicine, Albert Einstein College of Medicine, Bronx, NY (R.C.K.).
⁶¹ Division of Allergy & Clinical Immunology, Department of Medicine (R.A.M.), Johns Hopkins University School of Medicine, Baltimore, MD.
⁶² Kaiser Permanente Washington Health Research Institute, Seattle' WA (B.M.P.).
⁶³ Brown Foundation Institute of Molecular Medicine (M.F.), The University of Texas Health Science Center at Houston' Houston' TX.
⁶⁴ Human Genetics Center (M.F.), The University of Texas Health Science Center at Houston' Houston' TX.
⁶⁵ The Mindich Child Health and Development Institute (R.J.F.L.), The Icahn School of Medicine at Mount Sinai, New York, NY.
⁶⁶ Center for Human Genetics and Genomics, New York University Grossman School of Medicine, New York, NY (A.C.).
⁶⁷ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (E.B.).
⁶⁸ Division of Epidemiology, Department of Medicine (T.L.E.), Vanderbilt University Medical Center, Nashville, TN.
⁶⁹ College of Public Health, University of Kentucky, Lexington, KY (D.K.A.).

^# Contributed equally.

PMID: 35652341
PMCID: PMC9593435
DOI: 10.1161/HYPERTENSIONAHA.122.19324

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.

Keywords: allele; blood pressure; genome; hypertension; whole genome sequencing.

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Figures

**Figure 1.**
Design of the multi-stage genomic study of blood pressure phenotypes.

**Figure 2.**
Venn diagrams displaying suggestive BP signals across multi-ancestry and ancestry-specific analyses for: (A.) 113 novel BP loci; (B.) 122 potentially novel variants at previously reported BP loci; (C.) 69 genes; (D.) 262 sliding windows; and (E.) 279 signal driving variants from leave-one-out analyses. (F.) This diagram displays the overlap of suggestive BP signals across 235 SNVs identified by single variant analyses, including 113 from novel loci and 122 from previously reported loci, and 279 signal driving variants from leave-one-out analyses of suggestive genes and sliding windows.

**Figure 3.**
Regional association plots displaying signals at: (A.) *LOC100506274*; and (B.) *INSR*.

**Figure 4.**
Lachesis plots integrating aggregate and single variant signals at: (A.) *LEXM*; (B.) *ERBB4*; (C.) *LINC01520*; and (D.) *DAND5*.

See this image and copyright information in PMC

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous