Estudio de una estrategia alternativa de ingeniería genética para incrementar la fijación biológica de nitrógeno atmosférico

Para satisfacer los altos rendimientos que impulsan la agricultura moderna la aplicación de fertilizantes nitrogenados ha sido fundamental. Dado que la base de la producción industrial de los fertilizantes químicos esta basado en el uso de combustibles fósiles, estos, actualmente, incrementan el costo económico debido a la disminución constante de las reservas de petróleo. Además, dada la baja eficiencia en el uso del fertilizante aplicado por parte de las plantas y el alto impacto ambiental debido a la emisión de óxido nitroso, resulta necesario emprender la búsqueda de nuevas estrategias para aumentar la concentración del nitrógeno fijado. Una de las propuestas para disminuir la aplicación de fertilizantes es el uso de microorganismos fijadores de nitrógeno; que ya son ampliamente utilizados en leguminosas por su capacidad de establecer asociaciones simbióticas; las cuales, lamentablemente, aún no han sido encontradas entre los principales cultivos de cereales. El objetivo del presente trabajo es la producción de una técnica de ingeniería genética que permita obtener bacterias fijadoras de nitrógeno recombinantes capaces de asociarse a distintos cultivos vegetales incrementando la productividad de los mismos. Para ello, los genes que sintetizan la nitrogenasa (nif), que están co-localizados en una isla genómica, en Pseudomonas stutzeri A1501 se transfirieron, vía el cósmido recombinante X940, a un promotor del crecimiento vegetal, Pseudomonas protegens Pf-5. La bacteria recombinante obtenida, P. protegens Pf-5 X940, fue capaz de crecer en medios de cultivo deficientes en nitrógeno o con el agregado de amonio; mostró una alta actividad nitrogenasa, liberando al medio de cultivo cantidades significativas de amonio y presentó expresión de los genes nif, sugiriendo que el proceso de fijación, en esta bacteria, es constitutivo. Las inoculaciones de especies vegetales (arabidopsis, alfalfa, festuca alta y maíz)con Pf-5 X940 aumentaron la concentración de amonio en el suelo y la productividad de las plantas en condiciones deficientes de nitrógeno. Estos resultados inician un nuevo camino hacia la producción efectiva de inoculantes recombinantes para la fijación de nitrógeno en un amplio rango de cultivo

How to Improve Soil Anti-adhesion by Studying the Micro Relief of the Cuticle Surface of Digging Beetles: Exploring the Sulcophanaeus batesi Pronotum Using Translucent Replicas

For some years, we have been studying the microtopography of soil diggers beetles fromArgentina to find the anti-adhesion pattern to decrease a soil particle adhesion for agricultural machinery components. In 2018, we designed a macro topographic pattern for the upper surface of a steel shovel for tilling (agricultural tool) fromthe study of the microtopography (microrelief) of the cuticular surface of the pronotum of Diloboderus abderus (Coleoptera, Scarabaeidae), whose main feature is the presence of dimples randomly distributed.Fil: Guillén, Noelia Belén. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Setten, Lorena María. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Fil: Sánchez, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales; ArgentinaFil: Favret, Eduardo A. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Bot-graphy: An original technique for plant anatomy study based o metallography

Plant anatomists are recurrently looking for safer and faster methods to improve the observations of plants tissues, searching for images with better resolution. Nevertheless, some plant materials are difficult to handle due to their consistency, such as those with very hard tissue or with a combination of soft and hard tissues (e. g. parenchyma and sclerenchyma). In these cases, softening techniques have been developed [1]. But they do not completely solve this problem since their success depends on the thickness of the plant organ (Argentinian anatomists, pers. commun., 2020). To find a solution to this limitation, a standard procedure of metallography is proposed, as an alternative, for the study of plant organs. The standard technique consists of mounting the specimen in a castable resin (liquid polymer film), followed by grinding the sample with abrasive papers of different granulometry and observing the sample surface with optical reflection microscopy [2]. In this work, an example is shown, the basal internodes of 2.5 to 3 cm in diameter of sugarcane, harvested in Famaillá, Tucumán, Argentina.Fil: Montero, Ricardo. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Gomez, Fernando. Universidad Nacional de San Martin. Instituto de Tecnología Sabato; ArgentinaFil: Setten, Lorena. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Favret, Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Torres, Dario. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentin

Hydroxybutyrate prevents protein aggregation in the halotolerant bacterium Pseudomonas sp. CT13 under abiotic stress

Polyhydroxybutyrate (PHB), a typical carbon and energy storage compound, is widely found in Bacteria and Archae domains. This polymer is produced in response to conditions of physiological stress. PHB is composed of repeating units of β-hydroxybutyrate (R-3HB). It has been previously shown that R-3HB functions as an osmolyte in extremophile strains. In this study, Pseudomonas sp. CT13, a halotolerant bacterium, and its PHB synthase-minus mutant (phaC) were used to analyze the chaperone role of R-3HB. The production of this compound was found to be essential to salt stress resistance and positively correlated with salt concentration, suggesting that PHB monomer acts as a compatible solute in Pseudomonas sp. CT13. R-3HB accumulation was also associated with the prevention of protein aggregation under combined salt and thermal stresses in Pseudomonas sp. CT13. Physiological concentrations of R-3HB efficiently reduced citrate synthase (CS) aggregation and stabilized the enzymatic activities of CS during thermal stress. Docking analysis of the CS/R-3HB interaction predicted the stability of this complex under physiological concentrations of R-3HB. Thus, in vivo, in vitro and in silico analyses suggest that R-3HB can act as a chemical chaperone.Fil: Soto, Gabriela Cynthia. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Setten, Lorena María. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; Argentina. Universidad de Morón; ArgentinaFil: Lisi, Christian Daniel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Maurelis, Camila. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Mozzicafreddo, Matteo. Università degli Studi di Camerino; ItaliaFil: Cuccioloni, Massimiliano. Università degli Studi di Camerino; ItaliaFil: Angeletti, Mauro. Università degli Studi di Camerino; ItaliaFil: Ayub, Nicolás Daniel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; Argentin

Análisis y caracterización de poblaciones bacterianas solubilizadoras de P en un ensayo de larga duración con diferentes secuencias de cultivo

Se conoce bien que diferentes sistemas de uso y manejos de suelos afectan la abundancia, la actividad y la composición de la comunidad microbiana del suelo. En este trabajo se estudió el comportamiento de las poblaciones bacterianas cultivables y, en particular, las bacterias solubilizadoras de P (BSP) en muestras de suelo provenientes de un ensayo de larga duración con diferentes secuencias de cultivo. Los resultados obtenidos ponen en evidencia que el desmonte y el uso agrícola posterior luego de 11 años generó una disminución de la población de bacterias cultivables en general, y de las bacterias solubilizadoras de P en particular, con respecto al suelo prístino. Se obtuvieron aislamientos con una alta eficiencia de solubilización de P de los suelos provenientes de las diferentes rotaciones. Estos aislamientos eficientes se clasificaron taxonómicamente particular, la caracterización de los sobrenadantes de cultivos de los aislamientos Pseudomonas koreensis y Paenibacillus pabuli mostraron que son productoras de ácidos orgánicos. Los ensayos de inoculación combinada de estas dos cepas sobre plantas de maíz en cámara de cultivo pusieron de manifiesto un efecto sinérgico sobre la promoción del crecimiento de esta especie. Los resultados aquí presentados sugieren que si bien las poblaciones de BSP son más numerosas en suelos prístinos, determinadas rotaciones de cultivos a largo plazo favorecen el incremento de bacterias solubilizadoras más eficientes, un aspecto que debería tenerse en cuenta al diseñar futuras estrategias de búsqueda de potenciales bioinoculantes.It is well known that different soil use and management systems affect the abundance, activity and composition of the soil microbial community. In this work, the behavior of cultivable bacterial populations and, in particular, P (PSB) solubilizing bacteria in soil samples from a long-term trial with different culture sequences was studied. The results obtained show that the clearing and subsequent agricultural use after 11 years generated a decrease in the population of cultivable bacteria in general, and of P-solubilizing bacteria in particular, with respect to the pristine soil. Isolates with high P solubilization efficiency were obtained from the soils from the different rotations. These efficient isolates were taxonomically classified by 16S RNA analysis as belonging to the genera Bacillus, Paenibacillus, Pseudomonas and Xanthomonas. In particular, the characterization of the culture supernatants of the isolates Pseudomonas koreensis and Paenibacillus pabuli showed they are producers of organic acids. The combined inoculation tests of these two strains on maize plants in a culture chamber revealed a synergistic effect on the growth promotion of this species. The results presented here suggest that although PSB populations are more numerous in pristine soils, certain long-term crop rotations favor the increase of more efficient solubilizing bacteria, an aspect that should be considered when designing future search strategies for potential bioinoculants.Fil: Rorig, Marcela Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Rodríguez, Analía Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Frasier, Ileana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Setten, Lorena María. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Otero Estrada, Edit. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Solans, Mariana. Universidad Nacional del Comahue. Instituto de Investigaciones en Biodiversidad y Medioambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Scervino, José M. Universidad Nacional del Comahue. Instituto de Investigaciones en Biodiversidad y Medioambiente. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Grasso, Daniel Horacio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentin

Guía de buenas prácticas para la aplicación agrícola de digeridos

La presente Guía tiene por objeto brindar información sobre la adopción de buenas prácticas y la correcta aplicación agrícola de los digeridos provenientes de plantas de digestión anaeróbicas, fomentando el uso agrícola sustentable de estos materiales, considerando y tomando como base la Normativa existente en Argentina: Norma Técnica para la Aplicación Agrícola de Digerido Proveniente de Plantas de Digestión Anaeróbica (Resolución 19/2019 - Anexo G); desde aquí referenciada como Norma Técnica. La Guía propone transmitir de manera sencilla y amena lo establecido en la Norma Técnica y desarrollar un plan de aplicación con medidas tendientes a minimizar efectos adversos en la calidad del suelo y el agua, preservando la salud humana, animal y de los servicios ecosistémicos.Instituto de Ingeniería RuralFil: Mortola, Natalia Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Carfagno, Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Otero Estrada, Edit. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Roba, Marcos Andrés. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Ingeniería Rural. Laboratorio de Terramecánica e Implantación de Cultivos; ArgentinaFil: Eiza, Maximiliano J. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce. Unidad Integrada. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Sainz, Daiana S. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Rorig, Marcela Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Rodríguez, Analía Mercedes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Cosentino, Vanina Rosa Noemi. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Cátedra de Fertilidad y Fertilizantes; ArgentinaFil: Romaniuk, Romina Ingrid. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Brutti, Lucrecia Noemi. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Cátedra de Edafología; ArgentinaFil: Setten, Lorena María. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Manosalva, Jonatan. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Ingeniería Rural; ArgentinaFil: Butti, Mariano. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino; ArgentinaFil: Torti, María Juliana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino; ArgentinaFil: Branzini, Agustina. Ministerio de Agricultura, Ganadería y Pesca (MAGYP). Bioenergía; ArgentinaFil: Donato, Lidia Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Ingeniería Rural; Argentin

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding Information: GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file : Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe