JOSE EDUARDO KRIEGER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
- Focal adhesion signaling: Vascular smooth muscle cell contractility beyond calcium mechanisms(2021) RIBEIRO-SILVA, J. C.; MIYAKAWA, A. A.; KRIEGER, J. E.Smooth muscle cell (SMC) contractility is essential to vessel tone maintenance and blood pressure regulation. In response to vasoconstrictors, calcium-dependent mechanisms promote the activation of the regulatory myosin light chain, leading to increased cytoskeleton tension that favors cell shortening. In contrast, SMC maintain an intrinsic level of a contractile force independent of vasoconstrictor stimulation and sustained SMC contraction beyond the timescale of calcium-dependent mechanisms suggesting the involvement of additional players in the contractile response. Focal adhesions (FAs) are conceivable candidates that may influence SMC contraction. They are required for actin-based traction employed by cells to sense and respond to environmental cues in a process termed mechanotransduction. Depletion of FA proteins impairs SMC contractility, producing arteries that are prone to dissection because of a lack of mechanical stability. Here, we discuss the role of calcium-independent FA signaling mechanisms in SMC contractility. We speculate that FA signaling contributes to the genesis of a variety of SMC phenotypes and discuss the potential implications for mechanical homeostasis in normal and diseased states. ©2021 The Author(s).
- Variant genotypes associated with reduced expression of RhCE antigens among Brazilian blood donors(2021) DEZAN, Marcia Regina; OLIVEIRA, Valeria B.; CONRADO, Marina C. A. V.; ROCHA, Mateus Cardoso da; LUZ, Fabio; GALLUCCI, Antonio; PEREIRA, Alexandre C.; KRIEGER, Jose E.; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; DINARDO, Carla LuanaBackground The genetic diversity of the RHCE gene locus has been explored in diverse populations of different racial backgrounds. Data referring to the diversity of RHCE encoding weakened expression of C, c, E, and e in multiethnic populations is still incomplete. Methods Samples from Brazilian blood donors presenting reduced expression of C, c, E, or e on gel method were selected for the study. All exons and flanking introns of RHCE were genotyped though direct Sanger sequencing for the included donors. Results Sixty-six donors were included: 23 with weak C, 22 with weak c, 6 with weak E, 14 with weak e, and 1 with weak c and E. Among the samples with weak C, the following altered RH*C were encountered: RHCE*CeMA (n = 3), RHCE*Ce941C (n = 1), and RHCE*CeVA (n = 1). RHD*D-CE(4-7)-D was detected in six cases, RHCE*CE was presumably present in five cases, and seven cases were unexplained. Two altered alleles underlay the weak c phenotype: RHCE*ceJAL (n = 20) and RHCE*ce340T (n = 2), and two altered RHCE justified weak e: RHCE*ceMO (n = 6) and RHCE*ceJAL (n = 8). Three variant RHCE were associated with weak E: RHCE*cEJU (n = 4), RHCE*cE382C (n = 1), and RHCE*cEIV (n = 1). The RHCE*cE905A justified one case of weak c and E. Conclusion We describe the distribution of RHCE variants found in association with weak expression of C, c, E, and e in blood donors of multiethnic origin, which differs in comparison to that previously reported for people of African or Caucasian descent.
- High stretch induces endothelial dysfunction accompanied by oxidative stress and actin remodeling in human saphenous vein endothelial cells(2021) GIRAO-SILVA, T.; FONSECA-ALANIZ, M. H.; RIBEIRO-SILVA, J. C.; LEE, J.; PATIL, N. P.; DALLAN, L. A.; BAKER, A. B.; HARMSEN, M. C.; KRIEGER, J. E.; MIYAKAWA, A. A.The rate of the remodeling of the arterialized saphenous vein conduit limits the outcomes of coronary artery bypass graft surgery (CABG), which may be influenced by endothelial dysfunction. We tested the hypothesis that high stretch (HS) induces human saphenous vein endothelial cell (hSVEC) dysfunction and examined candidate underlying mechanisms. Our results showed that in vitro HS reduces NO bioavailability, increases inflammatory adhesion molecule expression (E-selectin and VCAM1) and THP-1 cell adhesion. HS decreases F-actin in hSVECs, but not in human arterial endothelial cells, and is accompanied by G-actin and cofilin's nuclear shuttling and increased reactive oxidative species (ROS). Pre-treatment with the broad-acting antioxidant N-acetylcysteine (NAC) supported this observation and diminished stretch-induced actin remodeling and inflammatory adhesive molecule expression. Altogether, we provide evidence that increased oxidative stress and actin cytoskeleton remodeling play a role in HS-induced saphenous vein endothelial cell dysfunction, which may contribute to predisposing saphenous vein graft to failure.
- Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure(2021) WANG, Heming; NOORDAM, Raymond; CADE, Brian E.; SCHWANDER, Karen; WINKLER, Thomas W.; LEE, Jiwon; SUNG, Yun Ju; BENTLEY, Amy R.; MANNING, Alisa K.; ASCHARD, Hugues; KILPELAINEN, Tuomas O.; ILKOV, Marjan; BROWN, Michael R.; HORIMOTO, Andrea R.; RICHARD, Melissa; BARTZ, Traci M.; VOJINOVIC, Dina; LIM, Elise; NIERENBERG, Jovia L.; LIU, Yongmei; CHITRALA, Kumaraswamynaidu; RANKINEN, Tuomo; MUSANI, Solomon K.; FRANCESCHINI, Nora; RAURAMAA, Rainer; ALVER, Maris; ZEE, Phyllis C.; HARRIS, Sarah E.; MOST, Peter J. van Der; NOLTE, Ilja M.; MUNROE, Patricia B.; PALMER, Nicholette D.; KUHNEL, Brigitte; WEISS, Stefan; WEN, Wanqing; HALL, Kelly A.; LYYTIKAINEN, Leo-Pekka; CONNELL, Jeff O.; EIRIKSDOTTIR, Gudny; LAUNER, Lenore J.; VRIES, Paul S. de; ARKING, Dan E.; CHEN, Han; BOERWINKLE, Eric; KRIEGER, Jose E.; SCHREINER, Pamela J.; SIDNEY, Stephen; SHIKANY, James M.; RICE, Kenneth; CHEN, Yii-Der Ida; GHARIB, Sina A.; BIS, Joshua C.; I, Annemarie Luik; IKRAM, M. Arfan; UITTERLINDEN, Andre G.; AMIN, Najaf; XU, Hanfei; LEVY, Daniel; HE, Jiang; LOHMAN, Kurt K.; ZONDERMAN, Alan B.; RICE, Treva K.; SIMS, Mario; WILSON, Gregory; SOFER, Tamar; RICH, Stephen S.; PALMAS, Walter; YAO, Jie; GUO, Xiuqing; I, Jerome Rotter; BIERMASZ, Nienke R.; MOOK-KANAMORI, Dennis O.; MARTIN, Lisa W.; BARAC, Ana; WALLACE, Robert B.; GOTTLIEB, Daniel J.; KOMULAINEN, Pirjo; HEIKKINEN, Sami; MAGI, Reedik; MILANI, Lili; METSPALU, Andres; STARR, John M.; MILANESCHI, Yuri; WAKEN, R. J.; GAO, Chuan; WALDENBERGER, Melanie; PETERS, Annette; STRAUCH, Konstantin; MEITINGER, Thomas; ROENNEBERG, Till; VOLKER, Uwe; DORR, Marcus; SHU, Xiao-Ou; MUKHERJEE, Sutapa; HILLMAN, David R.; KAHONEN, Mika; WAGENKNECHT, Lynne E.; GIEGER, Christian; GRABE, Hans J.; ZHENG, Wei; PALMER, Lyle J.; LEHTIMAKI, Terho; GUDNASON, Vilmundur; MORRISON, Alanna C.; PEREIRA, Alexandre C.; FORNAGE, Myriam; PSATY, Bruce M.; DUIJN, Cornelia M. van; LIU, Ching-Ti; KELLY, Tanika N.; EVANS, Michele K.; BOUCHARD, Claude; FOX, Ervin R.; KOOPERBERG, Charles; ZHU, Xiaofeng; LAKKA, Timo A.; ESKO, Tonu; NORTH, Kari E.; DEARY, Ian J.; SNIEDER, Harold; PENNINX, Brenda W. J. H.; GAUDERMAN, W. James; RAO, Dabeeru C.; REDLINE, Susan; HEEMST, Diana vanLong and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 P-joint < 5 x 10(-8)), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P-int < 5 x 10(-8)). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (P-int = 2 x 10(-6)). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (P-int < 10(-3)). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
- High-volume endurance exercise training stimulates hematopoiesis by increasing ACE NH2-terminal activity(2021) MAGALHAES, Flavio de Castro; FERNANDES, Tiago; BASSANEZE, Vinicius; MATTOS, Katt Coelho; SCHETTERT, Isolmar; MARQUES, Fabio Luiz Navarro; KRIEGER, Jose Eduardo; NAVA, Roberto; BARAUNA, Valerio Garrone; OLIVEIRA, Edilamar Menezes deOne of the health benefits of endurance exercise training (ET) is the stimulation of hematopoiesis. However, the mechanisms underlying ET-induced hematopoietic adaptations are understudied. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits proliferation of early hematopoietic progenitor cells. The angiotensin I-converting enzyme (ACE) NH2-terminal promotes hematopoiesis by inhibiting the anti-hematopoietic effect of Ac-SDKP. Here we demonstrate for the first time the role of ACE NH2-terminal in ET-induced hematopoietic adaptations. Wistar rats were subjected to 10 weeks of moderate-(T1) and high-(T2) volume swimming-training. Although both protocols induced classical ET-associated adaptations, only T2 increased plasma ACE NH2-domain activity (by 40%, P=0.0003) and reduced Ac-SDKP levels (by 50%, P<0.0001). T2 increased the number of hematopoietic stem cells (HSCs; similar to 200%, P=0.0008), early erythroid progenitor colonies (similar to 300%, P<0.0001) and reticulocytes (similar to 500%, P=0.0007), and reduced erythrocyte lifespan (similar to 50%, P=0.022). Following, Wistar rats were subjected to T2 or T2 combined with ACE NH2-terminal inhibition (captopril (Cap) treatment: 10 mg.kg(-1).day(-1)). T2 combined with ACE NH2-terminal inhibition prevented Ac-SDKP decrease and attenuated ET-induced hematopoietic adaptations. Altogether, our findings show that ET-induced hematopoiesis was at least partially associated with increased ACE NH2-terminal activity and reduction in the hematopoietic inhibitor Ac-SDKP.
- Dynamic Crosstalk between Vascular Smooth Muscle Cells and the Aged Extracellular Matrix(2021) RIBEIRO-SILVA, Joao Carlos; NOLASCO, Patricia; KRIEGER, Jose Eduardo; MIYAKAWA, Ayumi AureaVascular aging is accompanied by the fragmentation of elastic fibers and collagen deposition, leading to reduced distensibility and increased vascular stiffness. A rigid artery facilitates elastin to degradation by MMPs, exposing vascular cells to greater mechanical stress and triggering signaling mechanisms that only exacerbate aging, creating a self-sustaining inflammatory environment that also promotes vascular calcification. In this review, we highlight the role of crosstalk between smooth muscle cells and the vascular extracellular matrix (ECM) and how aging promotes smooth muscle cell phenotypes that ultimately lead to mechanical impairment of aging arteries. Understanding the underlying mechanisms and the role of associated changes in ECM during aging may contribute to new approaches to prevent or delay arterial aging and the onset of cardiovascular diseases.
- Novel Chest Radiographic Biomarkers for COVID-19 Using Radiomic Features Associated with Diagnostics and Outcomes(2021) FERREIRA JUNIOR, Jose Raniery; CARDENAS, Diego Armando Cardona; MORENO, Ramon Alfredo; REBELO, Marina de Fatima de Sa; KRIEGER, Jose Eduardo; GUTIERREZ, Marco AntonioCOVID-19 is a highly contagious disease that can cause severe pneumonia. Patients with pneumonia undergo chest X-rays (XR) to assess infiltrates that identify the infection. However, the radiographic characteristics of COVID-19 are similar to the other acute respiratory syndromes, hindering the imaging diagnosis. In this work, we proposed identifying quantitative/radiomic biomarkers for COVID-19 to support XR assessment of acute respiratory diseases. This retrospective study used different cohorts of 227 patients diagnosed with pneumonia; 49 of them had COVID-19. Automatically segmented images were characterized by 558 quantitative features, including gray-level histogram and matrices of co-occurrence, run-length, size zone, dependence, and neighboring gray-tone difference. Higher-order features were also calculated after applying square and wavelet transforms. Mann-Whitney U test assessed the diagnostic performance of the features, and the log-rank test assessed the prognostic value to predict Kaplan-Meier curves of overall and deterioration-free survival. Statistical analysis identified 51 independently validated radiomic features associated with COVID-19. Most of them were wavelet-transformed features; the highest performance was the small dependence matrix feature of ""low gray-level emphasis"" (area under the curve of 0.87, sensitivity of 0.85, p<0.001). Six features presented short-term prognostic value to predict overall and deterioration-free survival. The features of histogram ""mean absolute deviation"" and size zone matrix ""non-uniformity"" yielded the highest differences on Kaplan-Meier curves with a hazard ratio of 3.20 (p<0.05). The radiomic markers showed potential as quantitative measures correlated with the etiologic agent of acute infectious diseases and to stratify short-term risk of COVID-19 patients.
- Metabolomic Evaluation of Chronic Periodontal Disease in Older Adults(2021) RODRIGUES, Wellington F.; MIGUEL, Camila B.; AGOSTINHO, Ferdinando; V, Gabriela da Silva; LAZO-CHICA, Javier E.; SCAPIN, Sandra M. Naressi; NAPIMOGA, Marcelo H.; TRINDADE-DA-SILVA, Carlos A.; KRIEGER, Jose E.; PEREIRA, Alexandre da Costa; OLIVEIRA, Carlo J. Freire; SOARES, Siomar de Castro; UEIRA-VIEIRA, Carlos; KLEINJAN, AlexPeriodontal disease is an infectious inflammatory disease related to the destruction of supporting tissues of the teeth, leading to a functional loss of the teeth. Inflammatory molecules present in the exudate are catalyzed and form different metabolites that can be identified and quantified. Thus, we evaluated the inflammatory exudate present in crevicular fluid to identify metabolic biological markers for diagnosing chronic periodontal disease in older adults. Research participants were selected from long-term institutions in Brazil. Participants were individuals aged 65 years or older, healthy, or with chronic periodontal disease. Gas chromatography/mass spectrometry was used to evaluate potential biomarkers in 120 crevicular fluid samples. We identified 969 metabolites in the individuals. Of these, 15 metabolites showed a variable importance with projection score>1 and were associated with periodontal disease. Further analysis showed that among the 15 metabolites, two (5-aminovaleric acid and serine, 3TMS derivative) were found at higher concentrations in the crevicular fluid, indicating their potential diagnostic power for periodontal disease in older adults. Our findings indicated that some metabolites are present at high concentrations in the crevicular fluid in older adults with periodontal disease and can be used as biomarkers of periodontal disease.
- Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci(2021) FUENTES, Lisa de las; SUNG, Yun Ju; NOORDAM, Raymond; WINKLER, Thomas; FEITOSA, Mary F.; SCHWANDER, Karen; BENTLEY, Amy R.; BROWN, Michael R.; GUO, Xiuqing; MANNING, Alisa; CHASMAN, Daniel I.; ASCHARD, Hugues; BARTZ, Traci M.; BIELAK, Lawrence F.; CAMPBELL, Archie; CHENG, Ching-Yu; DORAJOO, Rajkumar; HARTWIG, Fernando P.; HORIMOTO, A. R. V. R.; LI, Changwei; LI-GAO, Ruifang; LIU, Yongmei; MARTEN, Jonathan; MUSANI, Solomon K.; NTALLA, Ioanna; RANKINEN, Tuomo; RICHARD, Melissa; SIM, Xueling; SMITH, Albert V.; TAJUDDIN, Salman M.; TAYO, Bamidele O.; VOJINOVIC, Dina; WARREN, Helen R.; XUAN, Deng; ALVER, Maris; BOISSEL, Mathilde; CHAI, Jin-Fang; CHEN, Xu; CHRISTENSEN, Kaare; DIVERS, Jasmin; EVANGELOU, Evangelos; GAO, Chuan; GIROTTO, Giorgia; HARRIS, Sarah E.; HE, Meian; HSU, Fang-Chi; KUEHNEL, Brigitte; LAGUZZI, Federica; LI, Xiaoyin; LYYTIKAINEN, Leo-Pekka; NOLTE, Ilja M.; POVEDA, Alaitz; RAURAMAA, Rainer; RIAZ, Muhammad; RUEEDI, Rico; SHU, Xiao-ou; SNIEDER, Harold; SOFER, Tamar; TAKEUCHI, Fumihiko; VERWEIJ, Niek; WARE, Erin B.; WEISS, Stefan; YANEK, Lisa R.; AMIN, Najaf; ARKING, Dan E.; ARNETT, Donna K.; BERGMANN, Sven; BOERWINKLE, Eric; BRODY, Jennifer A.; BROECKEL, Ulrich; BRUMAT, Marco; BURKE, Gregory; CABRERA, Claudia P.; CANOUIL, Mickael; CHEE, Miao Li; CHEN, Yii-Der Ida; COCCA, Massimiliano; CONNELL, John; SILVA, H. Janaka de; VRIES, Paul S. de; EIRIKSDOTTIR, Gudny; FAUL, Jessica D.; FISHER, Virginia; FORRESTER, Terrence; FOX, Ervin F.; FRIEDLANDER, Yechiel; GAO, He; GIGANTE, Bruna; GIULIANINI, Franco; GU, Chi Charles; GU, Dongfeng; HARRIS, Tamara B.; HE, Jiang; HEIKKINEN, Sami; HENG, Chew-Kiat; HUNT, Steven; IKRAM, M. Arfan; IRVIN, Marguerite R.; KAHONEN, Mika; KAVOUSI, Maryam; KHOR, Chiea Chuen; KILPELAINEN, Tuomas O.; KOH, Woon-Puay; KOMULAINEN, Pirjo; KRAJA, Aldi T.; KRIEGER, J. E.; LANGEFELD, Carl D.; LI, Yize; LIANG, Jingjing; LIEWALD, David C. M.; LIU, Ching-Ti; LIU, Jianjun; LOHMAN, Kurt K.; MAGI, Reedik; MCKENZIE, Colin A.; MEITINGER, Thomas; METSPALU, Andres; MILANESCHI, Yuri; MILANI, Lili; MOOK-KANAMORI, Dennis O.; NALLS, Mike A.; NELSON, Christopher P.; NORRIS, Jill M.; O'CONNELL, Jeff; OGUNNIYI, Adesola; PADMANABHAN, Sandosh; PALMER, Nicholette D.; PEDERSEN, Nancy L.; PERLS, Thomas; PETERS, Annette; PETERSMANN, Astrid; PEYSER, Patricia A.; POLASEK, Ozren; PORTEOUS, David J.; RAFFEL, Leslie J.; RICE, Treva K.; ROTTER, Jerome I.; RUDAN, Igor; RUEDA-OCHOA, Oscar-Leonel; SABANAYAGAM, Charumathi; SALAKO, Babatunde L.; SCHREINER, Pamela J.; SHIKANY, James M.; SIDNEY, Stephen S.; SIMS, Mario; SITLANI, Colleen M.; SMITH, Jennifer A.; STARR, John M.; STRAUCH, Konstantin; SWERTZ, Morris A.; TEUMER, Alexander; THAM, Yih Chung; UITTERLINDEN, Andre G.; VAIDYA, Dhananjay; ENDE, M. Yldau van der; WALDENBERGER, Melanie; WANG, Lihua; WANG, Ya-Xing; WEI, Wen-Bin; WEIR, David R.; WEN, Wanqing; YAO, Jie; YU, Bing; YU, Caizheng; YUAN, Jian-Min; ZHAO, Wei; ZONDERMAN, Alan B.; BECKER, Diane M.; BOWDEN, Donald W.; DEARY, Ian J.; DOERR, Marcus; ESKO, Tonu; FREEDMAN, Barry I.; FROGUEL, Philippe; GASPARINI, Paolo; GIEGER, Christian; JONAS, Jost Bruno; KAMMERER, Candace M.; KATO, Norihiro; LAKKA, Timo A.; LEANDER, Karin; LEHTIMAKI, Terho; MAGNUSSON, Patrik K. E.; MARQUES-VIDAL, Pedro; PENNINX, Brenda W. J. H.; SAMANI, Nilesh J.; HARST, Pim van der; WAGENKNECHT, Lynne E.; WU, Tangchun; ZHENG, Wei; ZHU, Xiaofeng; BOUCHARD, Claude; COOPER, Richard S.; CORREA, Adolfo; EVANS, Michele K.; GUDNASON, Vilmundur; HAYWARD, Caroline; HORTA, Bernardo L.; KELLY, Tanika N.; KRITCHEVSKY, Stephen B.; LEVY, Daniel; PALMAS, Walter R.; PEREIRA, A. C.; PROVINCE, Michael M.; PSATY, Bruce M.; RIDKER, Paul M.; ROTIMI, Charles N.; TAI, E. Shyong; DAM, Rob M. van; DUIJN, Cornelia M. van; WONG, Tien Yin; RICE, Kenneth; GAUDERMAN, W. James; MORRISON, Alanna C.; NORTH, Kari E.; KARDIA, Sharon L. R.; CAULFIELD, Mark J.; ELLIOTT, Paul; MUNROE, Patricia B.; FRANKS, Paul W.; RAO, Dabeeru C.; FORNAGE, MyriamEducational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, ""Some College"" (yes/no) and ""Graduated College"" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 x 10(-8)). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
- Evening preference correlates with regional brain volumes in the anterior occipital lobe(2021) EVANS, SL.; LEOCADIO-MIGUEL, M. A.; TAPOROSKI, T. P.; GOMEZ, L. M.; HORIMOTO, A. R. V. R.; ALKAN, E.; BEIJAMINI, F.; PEDRAZZOLI, M.; KNUTSON, K. L.; KRIEGER, J. E.; VALLADA, H. P.; STERR, A.; PEREIRA, A. C.; NEGRAO, A. B.; SCHANTZ, M. vonChronotype or diurnal preference is a questionnaire-based measure influenced both by circadian period and by the sleep homeostat. In order to further characterize the biological determinants of these measures, we used a hypothesis-free approach to investigate the association between the score of the morningness-eveningness questionnaire (MEQ) and the Munich chronotype questionnaire (MCTQ), as continuous variables, and volumetric measures of brain regions acquired by magnetic resonance imaging (MRI). Data were collected from the Baependi Heart Study cohort, based in a rural town in South-Eastern Brazil. MEQ and anatomical 1.5-T MRI scan data were available from 410 individuals, and MCTQ scores were available from a subset of 198 of them. The average MEQ (62.2 +/- 10.6) and MCTQ (average MSFsc 201 +/- 85 min) scores were suggestive of a previously reported strong general tendency toward morningness in this community. Setting the significance threshold at P > .002 to account for multiple comparisons, we observed a significant association between lower MEQ score (eveningness) and greater volume of the left anterior occipital sulcus (beta = -0.163, p = .001) of the occipital lobe. No significant associations were observed for MCTQ. This may reflect the smaller dataset for MCTQ, and/or the fact that MEQ, which asks questions about preferred timings, is more trait-like than the MCTQ, which asks questions about actual timings. The association between MEQ and a brain region dedicated to visual information processing is suggestive of the increasingly recognized fluidity in the interaction between visual and nonvisual photoreception and the circadian system, and the possibility that chronotype includes an element of masking.