Evidence map›Paper›PMID 35604428›Full record

ArticleCirculation. Genomic and precision medicine2022

Multi-Trait Genetic Analysis Reveals Clinically Interpretable Hypertension Subtypes.

Felix Vaura, Hyunkyung Kim, Miriam S Udler, FinnGen*, Veikko Salomaa, Leo Lahti, Teemu Niiranen

Abstract read
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Article in Circulation. Genomic and precision medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

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6citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Felix VauraDepartment of Internal Medicine (F.V., T.N.), University of Turku, Turku, Finland.ORCID 0000-0002-6036-889X
Hyunkyung KimDiabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston (H.K., M.U.).ORCID 0000-0001-7964-3073
Miriam S UdlerDiabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston (H.K., M.U.).ORCID 0000-0003-3824-9162
FinnGen*
Veikko SalomaaDepartment of Public Health & Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland (V.S., T.N.).ORCID 0000-0001-7563-5324
Leo LahtiDepartment of Computing (L.L.), University of Turku, Turku, Finland.ORCID 0000-0001-5537-637X
Teemu NiiranenDepartment of Internal Medicine (F.V., T.N.), University of Turku, Turku, Finland.ORCID 0000-0002-7394-7487

Funding

Clinical Implications of Genetically Defined Diabetes Subtypes and Application to Electronic Health Medical Record SystemsK23DK114551 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI UDLER, MIRIAM SARGON · 2017 to 2021
$1000k
Extension of Type 2 Diabetes Genetic Clustering to Populations of non-European AncestryR03DK131249 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI UDLER, MIRIAM SARGON · 2022 to 2023
$252k
NIDDK NIH HHS K23 DK114551NIDDK NIH HHS L30 DK106874NIDDK NIH HHS R03 DK131249
6 · The paper itself

Abstract

backgroundHypertension comprises a heterogeneous range of phenotypes. We asked whether underlying genetic structure could explain a part of this heterogeneity.

methodsOur study sample comprised N=198 148 FinnGen participants (56% women, mean age 58 years) and N=21 168 well-phenotyped FINRISK participants (53% women, mean age 50 years). First, we identified genetic hypertension components with an unsupervised Bayesian non-negative matrix factorization algorithm using public genome-wide association data for 144 genetic hypertension variants and 16 clinical traits. For these components, we computed their (1) cross-sectional associations with clinical traits in FINRISK using linear regression and (2) longitudinal associations with incident adverse outcomes in FinnGen using Cox regression.

resultsWe observed 4 genetic hypertension components corresponding to recognizable clinical phenotypes: obesity (high body mass index), dyslipidemia (low high-density lipoprotein cholesterol and high triglycerides), hypolipidemia (low low-density lipoprotein cholesterol and low total cholesterol), and short stature. In FINRISK, all hypertension components had robust associations with their respective clinical characteristics. In FinnGen, the Obesity component was associated with increased diabetes risk (hazard ratio per 1 SD increase 1.08 [Bonferroni corrected CI, 1.05-1.10]) and the Hypolipidemia component with increased autoimmune disease risk (hazard ratio per 1 SD increase 1.05 [Bonferroni corrected CI, 1.03-1.07]). In addition, all hypertension components were related to both hypertension and cardiovascular disease.

conclusionsOur unsupervised analysis demonstrates that the genetic basis of hypertension can be understood as a mixture of 4 broad, clinically interpretable components capturing disease heterogeneity. These components could be used to stratify individuals into specific genetic subtypes and, therefore, to benefit personalized health care and pharmaceutical research.

Indexed as

Genome-Wide Association StudyHypertensionBayes TheoremCholesterolCross-Sectional StudiesFemaleHumansMaleObesityPhenotypeRisk FactorsCholesterolcardiovascular diseasesepidemiologyhypertensionmedical geneticsprecision medicinerisk factorsrisk scores

Identifiers

PMID35604428
PMCPMC9558213

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