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3 results on '"Juhanson P"'

1. Targeting 160 candidate genes for blood pressure regulation with a genome-wide genotyping array.

Author

Siim Sõber, Elin Org, Katrin Kepp, Peeter Juhanson, Susana Eyheramendy, Christian Gieger, Peter Lichtner, Norman Klopp, Gudrun Veldre, Margus Viigimaa, Angela Döring, Kooperative Gesundheitsforschung in der Region Augsburg Study, Margus Putku, Piret Kelgo, HYPertension in ESTonia Study, Sue Shaw-Hawkins, Philip Howard, Abiodun Onipinla, Richard J Dobson, Stephen J Newhouse, Morris Brown, Anna Dominiczak, John Connell, Nilesh Samani, Martin Farrall, MRC British Genetics of Hypertension Study, Mark J Caulfield, Patricia B Munroe, Thomas Illig, H-Erich Wichmann, Thomas Meitinger, and Maris Laan

Subjects
Medicine, Science
Abstract

The outcome of Genome-Wide Association Studies (GWAS) has challenged the field of blood pressure (BP) genetics as previous candidate genes have not been among the top loci in these scans. We used Affymetrix 500K genotyping data of KORA S3 cohort (n = 1,644; Southern-Germany) to address (i) SNP coverage in 160 BP candidate genes; (ii) the evidence for associations with BP traits in genome-wide and replication data, and haplotype analysis. In total, 160 gene regions (genic region+/-10 kb) covered 2,411 SNPs across 11.4 Mb. Marker densities in genes varied from 0 (n = 11) to 0.6 SNPs/kb. On average 52.5% of the HAPMAP SNPs per gene were captured. No evidence for association with BP was obtained for 1,449 tested SNPs. Considerable associations (P50% of HAPMAP SNPs were tagged. In general, genes with higher marker density (>0.2 SNPs/kb) revealed a better chance to reach close to significance associations. Although, none of the detected P-values remained significant after Bonferroni correction (P

Published
2009
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2. Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion.

Author

Stephen Newhouse, Martin Farrall, Chris Wallace, Mimoza Hoti, Beverley Burke, Philip Howard, Abiodun Onipinla, Kate Lee, Sue Shaw-Hawkins, Richard Dobson, Morris Brown, Nilesh J Samani, Anna F Dominiczak, John M Connell, G Mark Lathrop, Jaspal Kooner, John Chambers, Paul Elliott, Robert Clarke, Rory Collins, Maris Laan, Elin Org, Peeter Juhanson, Gudrun Veldre, Margus Viigimaa, Susana Eyheramendy, Francesco P Cappuccio, Chen Ji, Roberto Iacone, Pasquale Strazzullo, Meena Kumari, Michael Marmot, Eric Brunner, Mark Caulfield, and Patricia B Munroe

Subjects
Medicine, Science
Abstract

WNK1--a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control--is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23-4.9), DBP 1.9 mmHg (95%CI:0.7-3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0-1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7 x 10(-3), combined with BRIGHT data-set p = 2 x 10(-4), n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p10 mmHg reduction) and risk for hypertension (OR

Published
2009
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3. Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion

Author

Eric J. Brunner, Abiodun Onipinla, Michael Marmot, G. Mark Lathrop, Susana Eyheramendy, Paul Elliott, Meena Kumari, Robert Clarke, Richard Dobson, Maris Laan, Nilesh J. Samani, Mark J. Caulfield, Philip Howard, Francesco P. Cappuccio, Chen Ji, Jaspal S. Kooner, John M. C. Connell, Kate L. Lee, Martin Farrall, Elin Org, Stephen Newhouse, Margus Viigimaa, Mimoza Hoti, Rory Collins, Morris J. Brown, Anna F. Dominiczak, Beverley Burke, Pasquale Strazzullo, Peeter Juhanson, Roberto Iacone, Catriona Wallace, Patricia B. Munroe, John C. Chambers, Gudrun Veldre, Sue Shaw-Hawkins, Wallace, Chris [0000-0001-9755-1703], Apollo - University of Cambridge Repository, Newhouse, S, Farrall, M, Wallace, C, Hoti, M, Burke, B, Howard, P, Onipinla, A, Lee, K, Shaw Hawkins, S, Dobson, R, Brown, M, Samani, Nj, Dominiczak, Af, Connell, Jm, Lathrop, Gm, Kooner, J, Chambers, J, Elliott, P, Clarke, R, Collins, R, Laan, M, Org, E, Juhanson, P, Veldre, G, Viigimaa, M, Eyheramendy, S, Cappuccio, Fp, Ji, C, Iacone, Roberto, Strazzullo, Pasquale, Kumari, M, Marmot, M, Brunner, E, Caulfield, M, and Munroe, Pb

Subjects
Male, Candidate gene, lcsh:Medicine, Blood Pressure, 030204 cardiovascular system & hematology, Essential hypertension, Cohort Studies, 0302 clinical medicine, WNK Lysine-Deficient Protein Kinase 1, WNK1 gene, lcsh:Science, Genetics and Genomics/Genetics of Disease, Genetics, 0303 health sciences, Multidisciplinary, Intracellular Signaling Peptides and Proteins, Middle Aged, Protein-Serine-Threonine Kinases, 3. Good health, Science & Technology - Other Topics, Female, Research Article, Adult, medicine.medical_specialty, General Science & Technology, Single-nucleotide polymorphism, Genetics and Genomics/Complex Traits, Biology, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Cardiovascular Disorders/Hypertension, Minor Histocompatibility Antigens, 03 medical and health sciences, Internal medicine, Genetics and Genomics/Population Genetics, MD Multidisciplinary, medicine, Humans, Polymorphism, Allele, 030304 developmental biology, Science & Technology, MULTIDISCIPLINARY SCIENCES, Haplotype, lcsh:R, Case-control study, Odds ratio, medicine.disease, QP, Endocrinology, Blood pressure, Case-Control Studies, Potassium, lcsh:Q
Abstract

WNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23–4.9), DBP 1.9 mmHg (95%CI:0.7–3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0–1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7×10−3, combined with BRIGHT data-set p = 2×10−4, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p−7). We identified several common haplotypes to be associated with increased BP and multiple low frequency haplotypes significantly associated with lower BP (>10 mmHg reduction) and risk for hypertension (OR

Published
2016

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