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
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits(2021) SUN, D.; RICHARD, M. A.; MUSANI, S. K.; SUNG, Y. J.; WINKLER, T. W.; SCHWANDER, K.; CHAI, J. F.; GUO, X.; KILPELäINEN, T. O.; VOJINOVIC, D.; ASCHARD, H.; HORTA, B. L.; LIU, C.-T.; BIELAK, L. F.; MOOK-KANAMORI, D. O.; MORRISON, A. C.; PEREIRA, A. C.; PSATY, B. M.; AMIN, N.; FOX, E. R.; KOOPERBERG, C.; WEN, W.; SIM, X.; BIERUT, L.; ROTTER, J. I.; BROWN, M. R.; KARDIA, S. L. R.; FRANCESCHINI, N.; RAO, D. C.; FORNAGE, M.; Lifelines Cohort Study; CHITRALA, K.; YANEK, L. R.; HARTWIG, F. P.; HORIMOTO, A. R. V. R.; LIU, Y.; MANNING, A. K.; NOORDAM, R.; SMITH, A. V.; HARRIS, S. E.; KüHNEL, B.; LYYTIKäINEN, L.-P.; NOLTE, I. M.; ARKING, D. E.; RAURAMAA, R.; MOST, P. J. van der; WANG, R.; WARE, E. B.; WEISS, S.; ARNETT, D. K.; BARAC, A.; BOERWINKLE, E.; BROECKEL, U.; CHAKRAVARTI, A.; CHEN, Y.-D. I.; CUPPLES, L. A.; LUIK, A. I.; DAVIGULUS, M. L.; FUENTES, L. de las; MUTSERT, R. de; VRIES, P. S. de; DELANEY, J. A. C.; ROUX, A. V. Diez; DöRR, M.; FAUL, J. D.; FRETTS, A. M.; GALLO, L. C.; MARTIN, L. W.; GRABE, H. J.; GU, C. C.; HARRIS, T. B.; HARTMAN, C. C. A.; HEIKKINEN, S.; IKRAM, M. A.; ISASI, C.; JOHNSON, W. C.; JONAS, J. B.; KAPLAN, R. C.; MEITINGER, T.; KOMULAINEN, P.; KRIEGER, J. E.; LEVY, D.; LIU, J.; LOHMAN, K.; MILANESCHI, Y.; O'CONNELL, J. R.; PALMAS, W. R.; PETERS, A.; PEYSER, P. A.; PULKKI-RåBACK, L.; RAFFEL, L. J.; ZHAO, W.; REINER, A. P.; RICE, K.; ROBINSON, J. G.; ROSENDAAL, F. R.; SCHMIDT, C. O.; SCHREINER, P. J.; SCHWETTMANN, L.; SHIKANY, J. M.; SHU, X.-O.; SIDNEY, S.; ZHU, X.; SIMS, M.; SMITH, J. A.; SOTOODEHNIA, N.; STRAUCH, K.; TAI, E. S.; TAYLOR, K. D.; UITTERLINDEN, A. G.; DUIJN, C. M. van; WALDENBERGER, M.; WEE, H.-L.; ZONDERMAN, A. B.; WEI, W.-B.; WILSON, G.; XUAN, D.; YAO, J.; ZENG, D.; BECKER, D. M.; DEARY, I. J.; GIEGER, C.; LAKKA, T. A.; LEHTIMäKI, T.; NORTH, K. E.; OLDEHINKEL, A. J.; BARTZ, T. M.; PENNINX, B. W. J. H.; SNIEDER, H.; WANG, Y.-X.; WEIR, D. R.; ZHENG, W.; EVANS, M. K.; GAUDERMAN, W. J.; GUDNASON, V.Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations. © 2020 The Author(s)
- 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.
- 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.
- Genome-Wide Association of Proprotein Convertase Subtilisin/Kexin Type 9 Plasma Levels in the ELSA-Brasil Study(2021) BENSENOR, Isabela; PADILHA, Kallyandra; LIMA, Isabella Ramos; SANTOS, Raul Dias; LAMBERT, Gilles; RAMIN-MANGATA, Stephane; BITTENCOURT, Marcio S.; GOULART, Alessandra C.; SANTOS, Itamar S.; MILL, Jose G.; KRIEGER, Jose E.; LOTUFO, Paulo A.; PEREIRA, Alexandre C.Pharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option to treat hypercholesterolemia, and plasma PCSK9 levels have been implicated in cardiovascular disease incidence. A number of genetic variants within the PCSK9 gene locus have been shown to modulate PCSK9 levels, but these only explain a very small percentage of the overall PCSK9 interindividual variation. Here we present data on the genetic association structure between PCSK9 levels and genom-wide genetic variation in a healthy sample from the general population. We performed a genome-wide association study of plasma PCSK9 levels in a sample of Brazilian individuals enrolled in the Estudo Longitudinal de Saude do Adulto cohort (n=810). Enrolled individuals were free from cardiovascular disease, diabetes and were not under lipid-lowering medication. Genome-wide genotyping was conducted using the Axiom_PMRA.r3 array, and imputation was performed using the TOPMED multi-ancestry sample panel as reference. Total PCSK9 plasma concentrations were determined using the Quantikine SPC900 ELISA kit. We observed two genome-wide significant loci and seven loci that reached the pre-defined value of p threshold of 1x10(-6). Significant variants were near KCNA5 and KCNA1, and LINC00353. Genetic variation at the PCSK9 locus was able to explain approximately 4% of the overall interindividual variations in PCSK9 levels. Colocalization analysis using eQTL data suggested RWDD3, ATXN7L1, KCNA1, and FAM177A1 to be potential mediators of some of the observed associations. Our results suggest that PCSK9 levels may be modulated by trans genetic variation outside of the PCSK9 gene and this may have clinical implications. Understanding both environmental and genetic predictors of PCSK9 levels may help identify new targets for cardiovascular disease treatment and contribute to a better assessment of the benefits of long-term PCSK9 inhibition.