Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = −0.62, P = 5.30 × 10−5) but not between CCT and primary open-angle glaucoma (r = −0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

RNA-RNA Noncovalent Interactions Investigated by Microspray Ionization Mass Spectrometry

Electrospray ionization mass spectrometry is playing an increasing role in the study of noncovalent interactions involving biomolecules. RNA-RNA complexes are important in many areas of biology, including RNA catalysis, RNA splicing, ribosome function, and gene regulation. Here, microelectrospray mass spectrometry (microESI-MS) is used to study noncovalent base-pairing interactions between RNA oligonucleotides, an area not previously explored by this technique. Using a set of complementary RNA oligonucleotides, we demonstrate the formation of the expected double-helical RNA complexes composed of three distinct oligonucleotides. The ability to study specific RNA noncovalent interactions by microESI-MS has the potential to provide a unique method by which to analyze and assign precise molecular masses to RNA-RNA complexes

Impacto da parada cardíaca induzida nas funções cognitivas após o implante de cardiodesfibrilador Impacto de la parada cardíaca inducida en las funciones cognitivas después del implante de desfibrilador cardiaco Impact of induced cardiac arrest on cognitive function after implantation of a cardioverter-defibrillator

JUSTIFICATIVA E OBJETIVOS: O cardiodesfibrilador implantável (CDI) foi introduzido na prática clínica em 1980 e é considerado o tratamento-padrão para indivíduos sob risco de desenvolverem disritmias ventriculares fatais. Com o intuito de garantir funcionamento adequado do cardiodesfibrilador, a energia necessária para o término da taquicardia ventricular ou da fibrilação ventricular deve ser determinada durante o implante, sendo esse procedimento chamado de teste do limiar de desfibrilação. Para a realização do teste é necessário que seja feita indução de fibrilação ventricular, para que o aparelho possa identificar o ritmo cardíaco e tratá-lo. O objetivo deste estudo foi verificar a ocorrência de disfunção cognitiva 24 horas após o implante de cardiodesfibrilador. MÉTODO: Foi selecionada uma amostra consecutiva de 30 pacientes com indicação de colocação de cardiodesfibrilador implantável (CDI) e 30 pacientes com indicação de implante de marca-passo (MP). Os pacientes foram avaliados nos seguintes momentos: 24 horas antes da colocação do CDI ou MP com ficha de avaliação pré-anestésica, Mini Exame do Estado Mental (MEEM) e Confusion Assessment Method (CAM). Durante o implante do CDI ou MP foram medidas as variáveis: número de paradas cardíacas e tempo total de parada cardíaca. Vinte e quatro horas após colocação do CDI ou MP, foram avaliadas as variáveis: MEEM e CAM. RESULTADOS: O teste de Fisher comprovou não haver diferença da freqüência de escores alterados do MEEM e do CAM entre os grupos antes e depois dos implantes. O tempo médio de PCR foi 7,06 segundos, com máximos e mínimos de 15,1 e 4,7 segundos. CONCLUSÕES: A indução de parada cardíaca durante o teste do limiar de desfibrilação não levou à disfunção cognitiva 24 horas após o implante de cardiodesfibrilador.<br>JUSTIFICATIVA Y OBJETIVOS: El desfibrilador cardiaco implantable (DCI) fue introducido en la práctica clínica en el 1980 y se considera el tratamiento estándar para individuos bajo el riesgo de desarrollar arritmias ventriculares fatales. Con el interés de garantizar el funcionamiento adecuado del desfibrilador cardiaco, la energía necesaria para el término de la taquicardia ventricular o de la fibrilación ventricular, debe ser determinada durante el implante, siendo este procedimiento llamado test del límite de desfibrilación. Para la realización del test es necesario que se haga la inducción de la fibrilación ventricular, para que el aparato pueda identificar el ritmo cardíaco y tratarlo. El objetivo de este estudio fue verificar la incidencia de disfunción cognitiva 24 horas después del implante del desfibrilador cardiaco. MÉTODO: Se seleccionó una muestra consecutiva de 30 pacientes con indicación de colocación de desfibrilador cardiaco implantable (DCI) y 30 pacientes con indicación de implante de marca-paso (MP). Los pacientes fueron evaluados en los siguientes momentos: 24 horas antes de la colocación del DCI o MP con ficha de evaluación preanestésica, Mini-Examen del Estado Mental (MEEM) y Confusion Assessment Method (CAM). Durante el implante del DCI o MP fueron medidas las variables: número de paradas cardíacas y tiempo total de parada cardíaca. Veinte y cuatro horas después de la colocación del DCI o MP, se evaluaron las variables: MEEM y CAM. RESULTADOS: El test de Fisher mostró que no había diferencia de la frecuencia de puntuaciones alteradas del MEEM y del CAM entre los grupos antes y después de los implantes. El tiempo promedio de PCR 7,06, con máximos y mínimos de 15,1 y 4,7 segundos. CONCLUSIONES: La inducción de parada cardíaca durante el test del límite de desfibrilación, no conllevó a la disfunción cognitiva veinte y cuatro horas después del implante del desfibrilador cardiaco.<br>BACKGROUND AND OBJECTIVES: Implantable cardioverter-defibrillators (ICD) were introduced in clinical practice in 1980 and they are considered the standard treatment for individuals at risk for fatal ventricular arrhythmias. To ensure proper working conditions, the energy necessary to interrupt ventricular tachycardia or ventricular fibrillation should be determined during implantation by a test called defibrillation threshold. For this test, it is necessary to induce ventricular fibrillation, which should be identified and treated by the device. The objective of the present study was to determine the frequency of cognitive dysfunction 24 hours after the implantation of a cardioverter-defibrillator. METHODS: Thirty consecutive patients with indication of cardioverter-defibrillator (ICD) placement and 30 patients with indication of implantable pacemaker (PM) were enrolled in this study. Patients were evaluated at the following moments: 24 hours before placement of the ICD or PM with a pre-anesthetic evaluation form, Mini Mental State Examination (MMSE), and Confusion Assessment Method (CAM); during implantation of the ICD or PM, the following parameters were determined: number of cardiac arrests and total time of cardiac arrest. Twenty-four hours after placement of the device, the following parameters were evaluated: MMSE and CAM. RESULTS: Differences in the frequency of altered MMSE and CAM scores between both groups before and after implantation were not detected by the Fisher Exact test. The mean time of cardiac arrest was 7.06 seconds, with a maximal of 15.1 and minimal of 4.7 seconds. CONCLUSIONS: Induction of cardiac arrest during defibrillation threshold testing did not cause cognitive dysfunction 24 hours after implantation of the cardioverter-defibrillator