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Complex genetic traits

My laboratory focuses on complex cardiovascular genetic traits, using molecular biology and computational methods.
Blood pressure and hypertension are among the key interests of this laboratory. HTN is quantitavely the major cardiovascular risk factor. Heritability estimates indicate that 30-60% of this risk is genetic. But the pathogenesis of essential HTN is unclear. We work with several large European and US-cohorts to better understand the genetics of essential HTN.

This laboratory is currently collaborating in a consortial effort of investigating blood pressure genetics by genomewide association (CHARGE and ICBP consortia) and we have conducted an analysis in which ~70,000 participants were genotyped for hundreds of thousands of SNPs. The preliminary results indicate that the genetic contribution to hypertension is the effect of multiple variants with small effect sizes (within the frequency range of >5%).

Large sample sizes and specialized analytical methods are required to demonstrate effects and evaluate their importance. Another main interest of this group are large scale sequencing efforts for the discovery of genetic determinants of cardiovascular disease at the lower end of the allele spectrum. Using the knowledge gained by the '1000 Genome Project' this laboratory is involved in analyzing datasets with our collaboration partners.
This laboratory also serves as DNA repository for several projects, most notably the 'RAHYCO' project, the 'Seychelles' project and the 'SkiPOGH' project in collaboration with Dr. A. Pechère HUG and Prof. M. Bochud, CHUV.

Group's publications

Effects of Rare and Common Blood Pressure Gene Variants on Essential Hypertension: Results From the Family Blood Pressure Program, CLUE, and Atherosclerosis Risk in Communities Studies.
CIRCULATION RESEARCH
2013 vol. 112(2) pp. 318-326
NGUYEN KD AND AL.

Genes for blood pressure: an opportunity to understand hypertension.
EUROPEAN HEART JOURNAL
2013 vol. pp. 0-
EHRET GB, CAULFIELD MJ

Influence of CYP2D6 Activity on Pre-emptive Analgesia by the N-Methyl-D-Aspartate Antagonist Dextromethorphan in a Randomized Controlled Trial of Acute Pain.
PAIN PHYSICIAN
2013 vol. 16(1) pp. 45-56
EHRET GB AND AL.

A multi-SNP locus-association method reveals a substantial fraction of the missing heritability.
AMERICAN JOURNAL OF HUMAN GENETICS
2012 vol. 91(5) pp. 863-871
EHRET GB AND AL.

KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron.
NATURE GENETICS
2012 vol. 44(4) pp. 456-460
LOUIS-DIT-PICARD H AND AL.

Next-generation sequencing of human mitochondrial reference genomes uncovers high heteroplasmy frequency.
PLOS COMPUTATIONAL BIOLOGY
2012 vol. 8(10) pp. 1002737-1002737
SOSA MX AND AL.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
NATURE
2011 vol. 478(7367) pp. 103-109
EHRET GB AND AL.

Variation in the checkpoint kinase 2 gene is associated with type 2 diabetes in multiple populations.
ACTA DIABETOLOGICA
2009 vol. pp. 0-
NORTH KE AND AL.

Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study.
EUROPEAN JOURNAL OF HUMAN GENETICS
2009 vol. 17(12) pp. 1650-1657
EHRET GB, O'CONNOR AA, WEDER A, COOPER RS, CHAKRAVARTI A

Positional identification of variants of Adamts16 linked to inherited hypertension.
HUMAN MOLECULAR GENETICS
2009 vol. 18(15) pp. 2825-2838
JOE B AND AL.

Common variants at ten loci modulate the QT interval duration in the QTSCD Study.
NATURE GENETICS
2009 vol. 41(4) pp. 407-414
PFEUFER A AND AL.

Genome-wide association study of blood pressure and hypertension.
NATURE GENETICS
2009 vol. 41(6) pp. 677-687
LEVY D AND AL.

Multiple loci associated with indices of renal function and chronic kidney disease.
NATURE GENETICS
2009 vol. 41(6) pp. 712-717
KÖTTGEN A AND AL.

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
NATURE GENETICS
2009 vol. 41(11) pp. 1191-1198
GANESH SK AND AL.

Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry.
NATURE GENETICS
2009 vol. 41(8) pp. 879-881
BENJAMIN E AND AL.

Replication of the Wellcome Trust genome-wide association study of essential hypertension: the Family Blood Pressure Program.
EUROPEAN JOURNAL OF HUMAN GENETICS
2008 vol. 16(12) pp. 1507-1511
EHRET GB AND AL.

Methadone-associated long QT syndrome: improving pharmacotherapy for dependence on illegal opioids and lessons learned for pharmacology.
EXPERT OPINION ON DRUG SAFETY
2007 vol. 6(3) pp. 289-303
EHRET GB, DESMEULES JA, BROERS B

An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension.
HUMAN MOLECULAR GENETICS
2007 vol. 16(14) pp. 1752-1764
WEN G AND AL.

Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.
PLOS GENETICS
2007 vol. 3(7) pp. 115-115
SCUTERI A AND AL.

Drug-induced long QT syndrome in injection drug users receiving methadone - High frequency in hospitalized patients and risk factors
ARCHIVES OF INTERNAL MEDICINE
2006 vol. 166 pp. 1280-1287
EHRET GB, VOIDE C, GEX-FABRY M, CHABERT J, SHAH D, BROERS B, PIGUET V, MUSSET T, GASPOZ JM, PERRIER A, DAYER P, DESMEULES JA

Systemic allergic reaction and diffuse bone pain after exposure to a preparation of betamethasone
EUROPEAN JOURNAL OF INTERNAL MEDICINE
2005 vol. 16 pp. 612-614
ERHET G, DELUZE C, DAYER P, DESMEULES JULES

QT interval prolongation in patients on methadone with concomitant drugs
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
2004 vol. 24 pp. 446-448
PIGUET V, DESMEULES J, EHRET G, STOLLER R, DAYER P

DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites.
JOURNAL OF BIOLOGICAL CHEMISTRY
2001 vol. 276(9) pp. 6675-6688
EHRET GB, REICHENBACH P, SCHINDLER U, HORVATH CM, FRITZ S, NABHOLZ M, BUCHER P

Research's domains




DATABASE-RESEARCH	GROUP OF CLINICAL PATIENT RESEARCH

Georg Ehret/François Mach	Head of group CV	Research subject	Members of the group


	Links about the group Dr Georg Ehret Fondation Recherches Médicales 64 Avenue de la Roseraie 1211 Genève 4 Suisse Georg.Ehret@hcuge.ch Tel.: +41 22 372 71 91 Group's web site / department Comments Pages updated the 17.11.2015		Reseach's subject \| Group's publications \| Research's domains Complex genetic traits My laboratory focuses on complex cardiovascular genetic traits, using molecular biology and computational methods. Blood pressure and hypertension are among the key interests of this laboratory. HTN is quantitavely the major cardiovascular risk factor. Heritability estimates indicate that 30-60% of this risk is genetic. But the pathogenesis of essential HTN is unclear. We work with several large European and US-cohorts to better understand the genetics of essential HTN. This laboratory is currently collaborating in a consortial effort of investigating blood pressure genetics by genomewide association (CHARGE and ICBP consortia) and we have conducted an analysis in which ~70,000 participants were genotyped for hundreds of thousands of SNPs. The preliminary results indicate that the genetic contribution to hypertension is the effect of multiple variants with small effect sizes (within the frequency range of >5%). Large sample sizes and specialized analytical methods are required to demonstrate effects and evaluate their importance. Another main interest of this group are large scale sequencing efforts for the discovery of genetic determinants of cardiovascular disease at the lower end of the allele spectrum. Using the knowledge gained by the '1000 Genome Project' this laboratory is involved in analyzing datasets with our collaboration partners. This laboratory also serves as DNA repository for several projects, most notably the 'RAHYCO' project, the 'Seychelles' project and the 'SkiPOGH' project in collaboration with Dr. A. Pechère HUG and Prof. M. Bochud, CHUV. Group's publications Effects of Rare and Common Blood Pressure Gene Variants on Essential Hypertension: Results From the Family Blood Pressure Program, CLUE, and Atherosclerosis Risk in Communities Studies. CIRCULATION RESEARCH 2013 vol. 112(2) pp. 318-326 NGUYEN KD AND AL. Genes for blood pressure: an opportunity to understand hypertension. EUROPEAN HEART JOURNAL 2013 vol. pp. 0- EHRET GB, CAULFIELD MJ Influence of CYP2D6 Activity on Pre-emptive Analgesia by the N-Methyl-D-Aspartate Antagonist Dextromethorphan in a Randomized Controlled Trial of Acute Pain. PAIN PHYSICIAN 2013 vol. 16(1) pp. 45-56 EHRET GB AND AL. A multi-SNP locus-association method reveals a substantial fraction of the missing heritability. AMERICAN JOURNAL OF HUMAN GENETICS 2012 vol. 91(5) pp. 863-871 EHRET GB AND AL. KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. NATURE GENETICS 2012 vol. 44(4) pp. 456-460 LOUIS-DIT-PICARD H AND AL. Next-generation sequencing of human mitochondrial reference genomes uncovers high heteroplasmy frequency. PLOS COMPUTATIONAL BIOLOGY 2012 vol. 8(10) pp. 1002737-1002737 SOSA MX AND AL. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. NATURE 2011 vol. 478(7367) pp. 103-109 EHRET GB AND AL. Variation in the checkpoint kinase 2 gene is associated with type 2 diabetes in multiple populations. ACTA DIABETOLOGICA 2009 vol. pp. 0- NORTH KE AND AL. Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study. EUROPEAN JOURNAL OF HUMAN GENETICS 2009 vol. 17(12) pp. 1650-1657 EHRET GB, O'CONNOR AA, WEDER A, COOPER RS, CHAKRAVARTI A Positional identification of variants of Adamts16 linked to inherited hypertension. HUMAN MOLECULAR GENETICS 2009 vol. 18(15) pp. 2825-2838 JOE B AND AL. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. NATURE GENETICS 2009 vol. 41(4) pp. 407-414 PFEUFER A AND AL. Genome-wide association study of blood pressure and hypertension. NATURE GENETICS 2009 vol. 41(6) pp. 677-687 LEVY D AND AL. Multiple loci associated with indices of renal function and chronic kidney disease. NATURE GENETICS 2009 vol. 41(6) pp. 712-717 KÖTTGEN A AND AL. Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. NATURE GENETICS 2009 vol. 41(11) pp. 1191-1198 GANESH SK AND AL. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. NATURE GENETICS 2009 vol. 41(8) pp. 879-881 BENJAMIN E AND AL. Replication of the Wellcome Trust genome-wide association study of essential hypertension: the Family Blood Pressure Program. EUROPEAN JOURNAL OF HUMAN GENETICS 2008 vol. 16(12) pp. 1507-1511 EHRET GB AND AL. Methadone-associated long QT syndrome: improving pharmacotherapy for dependence on illegal opioids and lessons learned for pharmacology. EXPERT OPINION ON DRUG SAFETY 2007 vol. 6(3) pp. 289-303 EHRET GB, DESMEULES JA, BROERS B An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension. HUMAN MOLECULAR GENETICS 2007 vol. 16(14) pp. 1752-1764 WEN G AND AL. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLOS GENETICS 2007 vol. 3(7) pp. 115-115 SCUTERI A AND AL. Drug-induced long QT syndrome in injection drug users receiving methadone - High frequency in hospitalized patients and risk factors ARCHIVES OF INTERNAL MEDICINE 2006 vol. 166 pp. 1280-1287 EHRET GB, VOIDE C, GEX-FABRY M, CHABERT J, SHAH D, BROERS B, PIGUET V, MUSSET T, GASPOZ JM, PERRIER A, DAYER P, DESMEULES JA Systemic allergic reaction and diffuse bone pain after exposure to a preparation of betamethasone EUROPEAN JOURNAL OF INTERNAL MEDICINE 2005 vol. 16 pp. 612-614 ERHET G, DELUZE C, DAYER P, DESMEULES JULES QT interval prolongation in patients on methadone with concomitant drugs JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY 2004 vol. 24 pp. 446-448 PIGUET V, DESMEULES J, EHRET G, STOLLER R, DAYER P DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites. JOURNAL OF BIOLOGICAL CHEMISTRY 2001 vol. 276(9) pp. 6675-6688 EHRET GB, REICHENBACH P, SCHINDLER U, HORVATH CM, FRITZ S, NABHOLZ M, BUCHER P Research's domains