Genome-wide association study of white-coat effect in hypertensive patients
Background: White-coat effect (WCE) confounds diagnosis and treatment of hypertension. The prevalence of white-coat hypertension is higher in Europe and Asia compared to other continents suggesting that genetic factors could play a role. Methods: To study genetic variation affecting WCE, we conducte...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-07-01
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| Series: | Blood Pressure |
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| Online Access: | http://dx.doi.org/10.1080/08037051.2019.1604066 |
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| author | Jenni M Rimpelä Teemu Niiranen Antti Jula Ilkka H Pörsti Antti Tikkakoski Aki Havulinna Terho Lehtimäki Veikko Salomaa Kimmo K Kontula Timo P Hiltunen |
| author_facet | Jenni M Rimpelä Teemu Niiranen Antti Jula Ilkka H Pörsti Antti Tikkakoski Aki Havulinna Terho Lehtimäki Veikko Salomaa Kimmo K Kontula Timo P Hiltunen |
| author_sort | Jenni M Rimpelä |
| collection | DOAJ |
| description | Background: White-coat effect (WCE) confounds diagnosis and treatment of hypertension. The prevalence of white-coat hypertension is higher in Europe and Asia compared to other continents suggesting that genetic factors could play a role. Methods: To study genetic variation affecting WCE, we conducted a two-stage genome-wide association study involving 1343 Finnish subjects. For the discovery stage, we used Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 206), providing the mean WCE values from up to four separate office/ambulatory recordings conducted on placebo. Associations with p values <1 × 10−5 were included in the replication step in three independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 182), Finn-Home study (n = 773) and Dietary, Lifestyle and Genetic Determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 182). Results: No single nucleotide polymorphisms reached genome-wide significance for association with either systolic or diastolic WCE. However, two loci provided suggestive evidence for association. A known coronary artery disease risk locus rs2292954 in SPG7 associated with systolic WCE (discovery p value = 2.2 × 10−6, replication p value = 0.03 in Finn-Home, meta-analysis p value 2.6 × 10−4), and rs10033652 in RASGEF1B with diastolic WCE (discovery p value = 4.9 × 10−6, replication p value = 0.04 in DILGOM, meta-analysis p value = 5.0 × 10−3). Conclusion: This study provides evidence for two novel candidate genes, SPG7 and RASGEF1B, associating with WCE. Our results need to be validated in even larger studies carried out in other populations. |
| first_indexed | 2024-03-12T00:39:11Z |
| format | Article |
| id | doaj.art-75daf4f67827468caf580984460b4797 |
| institution | Directory Open Access Journal |
| issn | 0803-7051 1651-1999 |
| language | English |
| last_indexed | 2024-03-12T00:39:11Z |
| publishDate | 2019-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Blood Pressure |
| spelling | doaj.art-75daf4f67827468caf580984460b47972023-09-15T08:45:22ZengTaylor & Francis GroupBlood Pressure0803-70511651-19992019-07-0128423924910.1080/08037051.2019.16040661604066Genome-wide association study of white-coat effect in hypertensive patientsJenni M Rimpelä0Teemu Niiranen1Antti Jula2Ilkka H Pörsti3Antti Tikkakoski4Aki Havulinna5Terho Lehtimäki6Veikko Salomaa7Kimmo K Kontula8Timo P Hiltunen9University of HelsinkiNational Institute for Health and Welfare, Helsinki, FinlandNational Institute for Health and Welfare, Helsinki, FinlandUniversity of Tampere and Tampere University HospitalTampere University HospitalFIMM, University of Helsinki, and Department of Health, National Institute for Health and WelfareUniversity of TampereNational Institute for Health and WelfareUniversity of HelsinkiUniversity of HelsinkiBackground: White-coat effect (WCE) confounds diagnosis and treatment of hypertension. The prevalence of white-coat hypertension is higher in Europe and Asia compared to other continents suggesting that genetic factors could play a role. Methods: To study genetic variation affecting WCE, we conducted a two-stage genome-wide association study involving 1343 Finnish subjects. For the discovery stage, we used Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 206), providing the mean WCE values from up to four separate office/ambulatory recordings conducted on placebo. Associations with p values <1 × 10−5 were included in the replication step in three independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 182), Finn-Home study (n = 773) and Dietary, Lifestyle and Genetic Determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 182). Results: No single nucleotide polymorphisms reached genome-wide significance for association with either systolic or diastolic WCE. However, two loci provided suggestive evidence for association. A known coronary artery disease risk locus rs2292954 in SPG7 associated with systolic WCE (discovery p value = 2.2 × 10−6, replication p value = 0.03 in Finn-Home, meta-analysis p value 2.6 × 10−4), and rs10033652 in RASGEF1B with diastolic WCE (discovery p value = 4.9 × 10−6, replication p value = 0.04 in DILGOM, meta-analysis p value = 5.0 × 10−3). Conclusion: This study provides evidence for two novel candidate genes, SPG7 and RASGEF1B, associating with WCE. Our results need to be validated in even larger studies carried out in other populations.http://dx.doi.org/10.1080/08037051.2019.1604066white-coat effecthypertensiongenegenome-widespg7rasgef1b |
| spellingShingle | Jenni M Rimpelä Teemu Niiranen Antti Jula Ilkka H Pörsti Antti Tikkakoski Aki Havulinna Terho Lehtimäki Veikko Salomaa Kimmo K Kontula Timo P Hiltunen Genome-wide association study of white-coat effect in hypertensive patients Blood Pressure white-coat effect hypertension gene genome-wide spg7 rasgef1b |
| title | Genome-wide association study of white-coat effect in hypertensive patients |
| title_full | Genome-wide association study of white-coat effect in hypertensive patients |
| title_fullStr | Genome-wide association study of white-coat effect in hypertensive patients |
| title_full_unstemmed | Genome-wide association study of white-coat effect in hypertensive patients |
| title_short | Genome-wide association study of white-coat effect in hypertensive patients |
| title_sort | genome wide association study of white coat effect in hypertensive patients |
| topic | white-coat effect hypertension gene genome-wide spg7 rasgef1b |
| url | http://dx.doi.org/10.1080/08037051.2019.1604066 |
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