Abstract
To identify stop-codon variants associated with blood pressure (BP). Illumina exome chip was genotyped in 5453 individuals of the population-based Malmö Diet and Cancer Study. We compared BP levels between carriers and noncarriers of all stop-codon variants found in at least 10 individuals and characterized these further based on literature evidence of functionality. Next, the association to ischemic stroke was evaluated in 2278 cases of ischemic stroke and 5969 controls. We identified 19 stop-codon variants with nominally significant BP associations (P < 0.05). One of these, located in the phosphodiesterase 11A (PDE11A) gene (R307X), has previously been reported to cause loss of PDE11A function and Cushing's syndrome in female carriers. In the Malmö Diet and Cancer Study, 1% of the population carried R307X and had age and sex-adjusted (mean, 95% confidence interval) 5.0, 0.29-9.7 (P = 0.038), and 3.3, 0.83-5.7 (P = 0.009) mmHg higher SBP and DBP than noncarriers and also significantly higher waist circumference and BMI. Among females, carriers of the R307X had age adjusted 8.3, 2.3-14 (P = 0.006) and 4.7, 1.7-7.7 (P = 0.002) mmHg higher SBP and DBP, 4.3, 0.84-7.8 (P = 0.015) cm higher waist circumference and 1.7, 0.30-3.1 (P ...Continue Reading
References
Sep 18, 1982·Lancet·E J Ross, D C Linch
Sep 1, 1995·Nature Genetics·J H HanssonR P Lifton
Aug 1, 1995·Nature Genetics·T MuneP C White
Nov 4, 1994·Cell·R A ShimketsJ W Findling
Jan 1, 1993·Journal of Internal Medicine·G BerglundS A Larsson
Oct 21, 2000·Hypertension·D LevyR H Myers
Apr 17, 2001·BMJ : British Medical Journal·F A McAlister, S E Straus
Aug 18, 2004·Journal of Hypertension·Cristiano FavaOlle Melander
Jun 4, 2005·Stroke; a Journal of Cerebral Circulation·Katarina JoodChristina Jern
Oct 14, 2005·Kidney International·Fredrik von WowernOlle Melander
Jun 13, 2006·Nature Genetics·Anelia HorvathConstantine A Stratakis
Apr 10, 2008·Nature Reviews. Genetics·Mark I McCarthyJoel N Hirschhorn
May 12, 2009·Nature Genetics·Daniel LevyCornelia M van Duijn
May 12, 2009·Nature Genetics·Christopher Newton-ChehPatricia B Munroe
Jul 2, 2009·JAMA : the Journal of the American Medical Association·Olle MelanderThomas J Wang
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher
May 5, 2010·Circulation·Sofia EnhörningOlle Melander
Jul 22, 2010·The New England Journal of Medicine·Teri A Manolio
Sep 13, 2011·Nature·UNKNOWN International Consortium for Blood Pressure Genome-Wide Association StudiesToby Johnson
May 25, 2012·Trends in Genetics : TIG·Sandosh PadmanabhanAnna F Dominiczak
May 30, 2012·Nature Genetics·Adam KiezunShamil R Sunyaev
Oct 11, 2012·JAMA : the Journal of the American Medical Association·Olle MelanderMarju Orho-Melander
Dec 25, 2012·Nature Genetics·Jeroen R HuygheKaren L Mohlke
Jan 10, 2013·PLoS Computational Biology·William S Bush, Jason H Moore
Mar 29, 2013·BMJ : British Medical Journal·Julia Kate PragueBenjamin Cameron Whitelaw
Jun 1, 2014·Genes·Christopher Ryan King, Dan L Nicolae
Citations
Mar 3, 2018·International Journal of Molecular Sciences·Alessia RussoGiuseppe Matullo
Jun 7, 2018·Scientific Reports·Emma N BardsleyDavid J Paterson
Nov 1, 2020·Molecular and Cellular Endocrinology·Isaac LevyConstantine A Stratakis
Jul 3, 2021·Pharmaceutics·Constantin-Tudor LucaStela Iurciuc
Jul 1, 2021·Cardiology and Therapy·Lyudmila Korostovtseva