Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

被引：47

作者：

Keaton, Jacob M. ^{[1
,2
]}

Kamali, Zoha ^{[3
,4
]}

Xie, Tian ^{[3
]}

Vaez, Ahmad ^{[3
,4
]}

Williams, Ariel ^{[1
]}

Goleva, Slavina B. ^{[1
]}

Ani, Alireza ^{[3
,4
]}

Evangelou, Evangelos ^{[5
,6
,7
]}

Hellwege, Jacklyn N. ^{[8
,9
,10
]}

Yengo, Loic ^{[11
]}

Young, William J. ^{[12
,13
]}

Traylor, Matthew ^{[12
,14
]}

Giri, Ayush ^{[2
,15
]}

Zheng, Zhili ^{[11
,16
]}

Zeng, Jian ^{[11
]}

Chasman, Daniel I. ^{[17
,18
,19
]}

Morris, Andrew P.

Caulfield, Mark J. ^{[12
,20
]}

Hwang, Shih-Jen ^{[21
,22
]}

Kooner, Jaspal S. ^{[23
]}

Conen, David ^{[24
]}

Attia, John R. ^{[25
]}

Morrison, Alanna C. ^{[26
]}

Loos, Ruth J. F. ^{[27
,28
,29
]}

Kristiansson, Kati ^{[30
]}

Schmidt, Reinhold ^{[31
]}

Hicks, Andrew A. ^{[32
,33
]}

Pramstaller, Peter P. ^{[32
,33
]}

Nelson, Christopher P. ^{[34
,35
]}

Samani, Nilesh J. ^{[34
,35
]}

Risch, Lorenz ^{[36
,37
]}

Gyllensten, Ulf ^{[38
]}

Melander, Olle ^{[39
,40
]}

Riese, Harriette ^{[41
]}

Wilson, James F. ^{[42
,43
]}

Campbell, Harry ^{[42
]}

Rich, Stephen S. ^{[44
]}

Psaty, Bruce M. ^{[45
,46
,47
]}

Lu, Yingchang ^{[48
]}

Rotter, Jerome I. ^{[49
]}

Guo, Xiuqing ^{[49
]}

Rice, Kenneth M. ^{[50
]}

Vollenweider, Peter ^{[51
,52
]}

Sundstroem, Johan ^{[53
,54
]}

Langenberg, Claudia ^{[55
,56
,57
]}

Tobin, Martin D. ^{[58
,59
]}

Giedraitis, Vilmantas ^{[60
]}

Luan, Jian'an ^{[55
]}

Tuomilehto, Jaakko ^{[30
,61
,62
]}

Kutalik, Zoltan ^{[63
,64
]}

机构：

[1] NHGRI, Ctr Precis Hlth Res, NIH, Bethesda, MD 20892 USA

[2] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, Nashville, TN USA

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[4] Isfahan Univ Med Sci, Dept Bioinformat, Esfahan, Iran

[5] Imperial Coll London, Dept Epidemiol & Biostat, London, England

[6] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece

[7] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Dept Biomed Res, Ioannina, Greece

[8] Vanderbilt Univ, Med Ctr, Dept Med, Div Genet Med, Nashville, TN USA

[9] Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA

[10] Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Biomed Lab Res & Dev, Nashville, TN USA

[11] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[12] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol, London, England

[13] Barts Hlth NHS Trust, St Bartholomews Hosp, Barts Heart Ctr, London, England

[14] Novo Nordisk Res Ctr Oxford, Dept Genet, Oxford, England

[15] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Div Quantitat Sci, Nashville, TN 37232 USA

[16] Broad Inst Harvard & MIT, Med & Populat Genet, Cambridge, MA USA

[17] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA

[18] Harvard Med Sch, Boston, MA 02115 USA

[19] Univ Manchester, Ctr Musculoskeletal Res, Ctr Genet & Genom Versus Arthrit, Manchester, Lancs, England

[20] Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Biomed Res Ctr, London, England

[21] NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA USA

[22] Boston Univ, Dept Biostat, Boston, MA 02215 USA

[23] Imperial Coll London, Natl Heart & Lung Inst, London, England

[24] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada

[25] Univ Newcastle, Fac Hlth & Med, Newcastle Upon Tyne, Tyne & Wear, England

[26] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA

[27] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[28] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA

[29] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark

[30] Finnish Inst Hlth & Welf, Dept Publ Hlth & Welf, Helsinki, Finland

[31] Med Univ Graz, Dept Neurol, Graz, Austria

[32] Eurac Res, Inst Biomed, Bolzano, Italy

[33] Univ Lubeck, Lubeck, Germany

[34] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England

[35] NIHR Leicester Biomed Res Ctr, Leicester, Leics, England

[36] Private Univ Principal Liechtenstein, Fac Med Sci, Triesen, Liechtenstein

[37] Dr Risch Anstalt, Dept Lab Med, Vaduz, Liechtenstein

[38] Uppsala Univ, Immunol Genet & Pathol, Uppsala, Sweden

[39] Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden

[40] Skane Univ Hosp, Dept Internal Med, Malmo, Sweden

[41] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands

[42] Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland

[43] Univ Edinburgh, Inst Genet & Canc, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[44] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[45] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[46] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[47] Univ Washington, Dept Hlth Syst & Populat Hlth, Seattle, WA 98195 USA

[48] Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Div Med Genet, Nashville, TN USA

[49] Harbor UCLA Med Ctr, Lundquist Inst Biomed Innovat, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA

[50] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

来源：

NATURE GENETICS | 2024年 / 56卷 / 05期

基金：

美国国家卫生研究院;

关键词：

PREDICTION MODELS; ASSOCIATION; VARIANTS; HYPERTENSION; LOCI; RARE; METAANALYSIS; EXPRESSION; IMPUTATION; DISCOVERY;

D O I：

10.1038/s41588-024-01714-w

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P<5x10(-8)) from the largest single-stage blood pressure (BP) genome-wide association study to date (n=1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P=2.22x10(-126)) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P=4.13x10(-44)) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, Delta AUROC, 0.035, P=1.98x10(-34)). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

引用

页码：778 / +

页数：36

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