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2. Identifying genetic determinants of inflammatory pain in mice using a large-scale gene-targeted screen

Author

Wotton, Janine M, Peterson, Emma, Flenniken, Ann M, Bains, Rasneer S, Veeraragavan, Surabi, Bower, Lynette R, Bubier, Jason A, Parisien, Marc, Bezginov, Alexandr, Haselimashhadi, Hamed, Mason, Jeremy, Moore, Michayla A, Stewart, Michelle E, Clary, Dave A, Delbarre, Daniel J, Anderson, Laura C, D'Souza, Abigail, Goodwin, Leslie O, Harrison, Mark E, Huang, Ziyue, Mckay, Matthew, Qu, Dawei, Santos, Luis, Srinivasan, Subhiksha, Urban, Rachel, Vukobradovic, Igor, Ward, Christopher S, Willett, Amelia M, Consortium, The International Mouse Phenotyping, Braun, Robert E, Brown, Steve DM, Dickinson, Mary E, Heaney, Jason D, Kumar, Vivek, Lloyd, KC Kent, Mallon, Ann-Marie, McKerlie, Colin, Murray, Stephen A, Nutter, Lauryl MJ, Parkinson, Helen, Seavitt, John R, Wells, Sara, Samaco, Rodney C, Chesler, Elissa J, Smedley, Damian, Diatchenko, Luda, Baumbauer, Kyle M, Young, Erin E, Bonin, Robert P, Mandillo, Silvia, and White, Jacqueline K

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Human Genome, Pain Research, Genetics, Biotechnology, Chronic Pain, 2.1 Biological and endogenous factors, Generic health relevance, Animals, Freund's Adjuvant, Mice, Mice, Knockout, Nociception, Pain, Pain Measurement, Nocifensive behavior, Sensitization, Formalin, Hargreaves, von Frey, Complete Freund's adjuvant, Single-gene knockout mouse, Screen, IMPC, Comorbidity, Autism, International Mouse Phenotyping Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Anesthesiology, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

AbstractIdentifying the genetic determinants of pain is a scientific imperative given the magnitude of the global health burden that pain causes. Here, we report a genetic screen for nociception, performed under the auspices of the International Mouse Phenotyping Consortium. A biased set of 110 single-gene knockout mouse strains was screened for 1 or more nociception and hypersensitivity assays, including chemical nociception (formalin) and mechanical and thermal nociception (von Frey filaments and Hargreaves tests, respectively), with or without an inflammatory agent (complete Freund's adjuvant). We identified 13 single-gene knockout strains with altered nocifensive behavior in 1 or more assays. All these novel mouse models are openly available to the scientific community to study gene function. Two of the 13 genes (Gria1 and Htr3a) have been previously reported with nociception-related phenotypes in genetically engineered mouse strains and represent useful benchmarking standards. One of the 13 genes (Cnrip1) is known from human studies to play a role in pain modulation and the knockout mouse reported herein can be used to explore this function further. The remaining 10 genes (Abhd13, Alg6, BC048562, Cgnl1, Cp, Mmp16, Oxa1l, Tecpr2, Trim14, and Trim2) reveal novel pathways involved in nociception and may provide new knowledge to better understand genetic mechanisms of inflammatory pain and to serve as models for therapeutic target validation and drug development.

Published
2022

4. Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain

Author

Parisien, Marc, van Reij, Roel R.I., Khoury, Samar, Koseli, Eda, Karaky, Mohamad, Silva, Jaqueline R., Taheri, Golnar, van den Hoogen, Nynke J., Peng, Garrie, Allegri, Massimo, De Gregori, Manuela, Chelly, Jacques E., Rakel, Barbara A., Aasvang, Eske K., Kehlet, Henrik, Buhre, Wolfgang F.F.A., Bryant, Camron D., Damaj, M. Imad, King, Irah L., Ghasemlou, Nader, Mogil, Jeffrey S., Joosten, Elbert A.J., and Diatchenko, Luda

Published
2024
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5. A prognostic risk score for development and spread of chronic pain

Author

Tanguay-Sabourin, Christophe, Fillingim, Matt, Guglietti, Gianluca V., Zare, Azin, Parisien, Marc, Norman, Jax, Sweatman, Hilary, Da-ano, Ronrick, Heikkala, Eveliina, Perez, Jordi, Karppinen, Jaro, Villeneuve, Sylvia, Thompson, Scott J., Martel, Marc O., Roy, Mathieu, Diatchenko, Luda, and Vachon-Presseau, Etienne

Published
2023
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8. Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis

Author

Bang, Sangsu, Jiang, Changyu, Xu, Jing, Chandra, Sharat, McGinnis, Aidan, Luo, Xin, He, Qianru, Li, Yize, Wang, Zilong, Ao, Xiang, Parisien, Marc, de Araujo, Lorenna Oliveira Fernandes, Esfahani, Sahel Jahangiri, Zhang, Qin, Tonello, Raquel, Berta, Temugin, Diatchenko, Luda, and Ji, Ru-Rong

Subjects
Care and treatment, Physiological aspects, Analysis, Models, Risk factors, Health aspects, Homeostasis -- Analysis, Potassium channels -- Physiological aspects -- Health aspects, Ligands (Biochemistry) -- Physiological aspects -- Health aspects, Polyneuropathies -- Risk factors -- Models -- Care and treatment, Glia -- Physiological aspects -- Health aspects, Neuroglia -- Physiological aspects -- Health aspects
Abstract

Introduction Satellite glial cells (SGCs) reside in the peripheral nervous system (PNS), where they wrap around neuronal cell bodies and form a complete envelope, allowing for close neuron-SGC interactions in [...], G protein-coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR with largely unknown functions. Here, we report that Gpr37l1/GRP37L1 ranks among the most highly expressed GPCR transcripts in mouse and human dorsal root ganglia (DRGs) and is selectively expressed in satellite glial cells (SGCs). Peripheral neuropathy induced by streptozotoxin (STZ) and paclitaxel (PTX) led to reduced GPR37L1 expression on the plasma membrane in mouse and human DRGs. Transgenic mice with Gpr37l1 deficiency exhibited impaired resolution of neuropathic pain symptoms following PTX- and STZ-induced pain, whereas overexpression of Gpr37l1 in mouse DRGs reversed pain. GPR37L1 is coexpressed with potassium channels, including KCNj10 (Kir4.1) in mouse SGCs and both KCNJ3 (Kir3.1) and KCNj10 in human SGCs. GPR37L1 regulates the surface expression and function of the potassium channels. Notably, the proresolving lipid mediator maresin 1 (MaR1) serves as a ligand of GPR37L1 and enhances KCNJ10- or KCNJ3-mediated potassium influx in SGCs through GPR37L1. Chemotherapy suppressed KCNJ10 expression and function in SGCs, which MaR1 rescued through GPR37L1. Finally, genetic analysis revealed that the GPR37L1-E296K variant increased chronic pain risk by destabilizing the protein and impairing the protein's function. Thus, GPR37L1 in SGCs offers a therapeutic target for the protection of neuropathy and chronic pain.

Published
2024
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10. Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons

Author

Farinotti, Alex Bersellini, Wigerblad, Gustaf, Nascimento, Diana, Bas, Duygu B, Urbina, Carlos Morado, Nandakumar, Kutty Selva, Sandor, Katalin, Xu, Bingze, Abdelmoaty, Sally, Hunt, Matthew A, Möller, Kristina Ängeby, Baharpoor, Azar, Sinclair, Jon, Jardemark, Kent, Lanner, Johanna T, Khmaladze, Ia, Borm, Lars E., Zhang, Lu, Wermeling, Fredrik, Cragg, Mark S, Lengqvist, Johan, Chabot-Doré, Anne-Julie, Diatchenko, Luda, Belfer, Inna, Collin, Mattias, Kultima, Kim, Heyman, Birgitta, Jimenez-Andrade, Juan M., Codeluppi, Simone, Holmdahl, Rikard, and Svensson, Camilla I

Subjects
Quantitative Biology - Neurons and Cognition, Quantitative Biology - Tissues and Organs
Abstract

Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcR{\gamma} chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcR{\gamma} chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcR{\gamma} chain-deficient mice or mice lacking activating Fc{\gamma}Rs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.

Published
2019
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12. Optimizing and Accelerating the Development of Precision Pain Treatments for Chronic Pain: IMMPACT Review and Recommendations

Author

Edwards, Robert R., Schreiber, Kristin L., Dworkin, Robert H., Turk, Dennis C., Baron, Ralf, Freeman, Roy, Jensen, Troels S., Latremoliere, Alban, Markman, John D., Rice, Andrew S.C., Rowbotham, Michael, Staud, Roland, Tate, Simon, Woolf, Clifford J., Andrews, Nick A., Carr, Daniel B., Colloca, Luana, Cosma-Roman, Doina, Cowan, Penney, Diatchenko, Luda, Farrar, John, Gewandter, Jennifer S., Gilron, Ian, Kerns, Robert D., Marchand, Serge, Niebler, Gwendolyn, Patel, Kushang V., Simon, Lee S., Tockarshewsky, Tina, Vanhove, Geertrui F., Vardeh, Daniel, Walco, Gary A., Wasan, Ajay D., and Wesselmann, Ursula

Published
2023
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13. Sodium-calcium exchanger-3 regulates pain “wind-up”: From human psychophysics to spinal mechanisms

Author

Trendafilova, Teodora, Adhikari, Kaustubh, Schmid, Annina B., Patel, Ryan, Polgár, Erika, Chisholm, Kim I., Middleton, Steven J., Boyle, Kieran, Dickie, Allen C., Semizoglou, Evangelia, Perez-Sanchez, Jimena, Bell, Andrew M., Ramirez-Aristeguieta, Luis Miguel, Khoury, Samar, Ivanov, Aleksandar, Wildner, Hendrik, Ferris, Eleanor, Chacón-Duque, Juan-Camilo, Sokolow, Sophie, Saad Boghdady, Mohamed A., Herchuelz, André, Faux, Pierre, Poletti, Giovanni, Gallo, Carla, Rothhammer, Francisco, Bedoya, Gabriel, Zeilhofer, Hanns Ulrich, Diatchenko, Luda, McMahon, Stephen B., Todd, Andrew J., Dickenson, Anthony H., Ruiz-Linares, Andres, and Bennett, David L.

Published
2022
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14. Disentangling the genetics of lean mass.

Author

Karasik, David, Zillikens, M, Hsu, Yi-Hsiang, Aghdassi, Ali, Akesson, Kristina, Amin, Najaf, Barroso, Inês, Bennett, David, Bertram, Lars, Bochud, Murielle, Borecki, Ingrid, Broer, Linda, Buchman, Aron, Byberg, Liisa, Campbell, Harry, Campos-Obando, Natalia, Cauley, Jane, Cawthon, Peggy, Chambers, John, Chen, Zhao, Cho, Nam, Choi, Hyung, Chou, Wen-Chi, Cummings, Steven, de Groot, Lisette, De Jager, Phillip, Demuth, Ilja, Diatchenko, Luda, Econs, Michael, Eiriksdottir, Gudny, Enneman, Anke, Eriksson, Joel, Eriksson, Johan, Estrada, Karol, Evans, Daniel, Feitosa, Mary, Fu, Mao, Gieger, Christian, Grallert, Harald, Gudnason, Vilmundur, Lenore, Launer, Hayward, Caroline, Hofman, Albert, Homuth, Georg, Huffman, Kim, Husted, Lise, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Johnson, Toby, Biffar, Reiner, Jordan, Joanne, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas, Klopp, Norman, Kloth, Jacqueline, Koller, Daniel, Kooner, Jaspal, Kraus, William, Kritchevsky, Stephen, Kutalik, Zoltán, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Langdahl, Bente, Lerch, Markus, Lewis, Joshua, Lill, Christina, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Livshits, Gregory, Ljunggren, Östen, Loos, Ruth, Lorentzon, Mattias, Luan, Jianan, Luben, Robert, Malkin, Ida, McGuigan, Fiona, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Michaëlsson, Karl, Mitchell, Braxton, Morris, Andrew, Mosekilde, Leif, Nethander, Maria, Newman, Anne, OConnell, Jeffery, Oostra, Ben, Orwoll, Eric, Palotie, Aarno, Peacock, Munro, Perola, Markus, and Peters, Annette

Subjects
ADAMTS Proteins, Absorptiometry, Photon, Adipose Tissue, Adolescent, Adult, Aged, Aged, 80 and over, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Composition, Body Fluid Compartments, Electric Impedance, Extracellular Matrix Proteins, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Muscle, Skeletal, Phenotype, Polymorphism, Single Nucleotide, RNA-Binding Proteins, Receptor, Melanocortin, Type 4, Versicans, White People, Young Adult
Abstract

BACKGROUND: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. OBJECTIVES: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. METHODS: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). RESULTS: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as sumo wrestler loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed body builder loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in body builder loci were associated with metabolic protection. CONCLUSIONS: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

Published
2019

15. Single-cell RNA sequencing reveals time- and sex-specific responses of mouse spinal cord microglia to peripheral nerve injury and links ApoE to chronic pain

Author

Tansley, Shannon, Uttam, Sonali, Ureña Guzmán, Alba, Yaqubi, Moein, Pacis, Alain, Parisien, Marc, Deamond, Haley, Wong, Calvin, Rabau, Oded, Brown, Nicole, Haglund, Lisbet, Ouellet, Jean, Santaguida, Carlo, Ribeiro-da-Silva, Alfredo, Tahmasebi, Soroush, Prager-Khoutorsky, Masha, Ragoussis, Jiannis, Zhang, Ji, Salter, Michael W., Diatchenko, Luda, Healy, Luke M., Mogil, Jeffrey S., and Khoutorsky, Arkady

Published
2022
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16. The more you test, the more you find: Smallest P-values become increasingly enriched with real findings as more tests are conducted

Author

Vsevolozhskaya, Olga A., Kuo, Chia-Ling, Ruiz, Gabriel, Diatchenko, Luda, and Zaykin, Dmitri V.

Subjects
Quantitative Biology - Genomics, Statistics - Methodology
Abstract

Increasing accessibility of data to researchers makes it possible to conduct massive amounts of statistical testing. Rather than follow a carefully crafted set of scientific hypotheses with statistical analysis, researchers can now test many possible relations and let P-values or other statistical summaries generate hypotheses for them. Genetic epidemiology field is an illustrative case in this paradigm shift. Driven by technological advances, testing a handful of genetic variants in relation to a health outcome has been abandoned in favor of agnostic screening of the entire genome, followed by selection of top hits, e.g., by selection of genetic variants with the smallest association P-values. At the same time, nearly total lack of replication of claimed associations that has been shaming the field turned to a flow of reports whose findings have been robustly replicating. Researchers may have adopted better statistical practices by learning from past failures, but we suggest that a steep increase in the amount of statistical testing itself is an important factor. Regardless of whether statistical significance has been reached, an increased number of tested hypotheses leads to enrichment of smallest P-values with genuine associations. In this study, we quantify how the expected proportion of genuine signals (EPGS) among top hits changes with an increasing number of tests. When the rate of occurrence of genuine signals does not decrease too sharply to zero as more tests are performed, the smallest P-values are increasingly more likely to represent genuine associations in studies with more tests.

Published
2016

17. Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Author

Zillikens, M Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M, Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L, Kutalik, Zoltán, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Hua Zhao, Jing, Zhang, Weihua, Aghdassi, Ali, Åkesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Inês, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos Obanda, Natalia, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Jin Choi, Hyung, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie AM, Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W, Erdos, Mike, Eriksson, Johan G, Eriksson, Joel, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L, Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L, Hayward, Caroline, Hofman, Albert, Hoffman, Eric P, Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J, Hubbard, Alan, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline SL, Koistinen, Heikki A, Kraus, William E, Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Launer, Lenore J, Lee, Jong-Young, Lerch, Markus M, Lewis, Joshua R, Lind, Lars, Lindgren, Cecilia, and Liu, Yongmei

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome
Abstract

A correction to this article has been published and is linked from the HTML version of this article.

Published
2017

18. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Author

Zillikens, M Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M, Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L, Kutalik, Zoltán, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Hua Zhao, Jing, Zhang, Weihua, Aghdassi, Ali, Åkesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Inês, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos Obanda, Natalia, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Jin Choi, Hyung, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie AM, Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W, Erdos, Mike, Eriksson, Johan G, Eriksson, Joel, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L, Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L, Hayward, Caroline, Hofman, Albert, Hoffman, Eric P, Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J, Hubbard, Alan, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline SL, Koistinen, Heikki A, Kraus, William E, Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Launer, Lenore J, Lee, Jong-Young, Lerch, Markus M, Lewis, Joshua R, Lind, Lars, Lindgren, Cecilia, and Liu, Yongmei

Subjects
Humans, Thinness, 17-Hydroxysteroid Dehydrogenases, Aldehyde Oxidoreductases, Extracellular Matrix Proteins, Body Composition, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Regulatory Elements, Transcriptional, Versicans, Genome-Wide Association Study, Insulin Receptor Substrate Proteins, ADAMTS Proteins, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Human Genome, Genetics, 1.1 Normal biological development and functioning
Abstract

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p

Published
2017

23. Adipose-Derived miR-133a-3p And Its Role in Mechanical Sensitivity in Chronic Primary Pain Conditions

Author

Hernandez, Nathaniel P., primary, Chen, Jiegen, additional, Zhang, Xin, additional, Wang, Yaomin, additional, Gao, Xianglong, additional, Ciszek, Brittney P., additional, Kanke, Matt, additional, Karaky, Mohamad, additional, Klein, Marguerita E., additional, Sethupathy, Praveen, additional, Diatchenko, Luda, additional, and Nackley, Andrea G., additional

Published
2024
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24. Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain

Author

Medische staf Anesthesiologie, Circulatory Health, Parisien, Marc, van Reij, Roel R.I., Khoury, Samar, Koseli, Eda, Karaky, Mohamad, Silva, Jaqueline R., Taheri, Golnar, van den Hoogen, Nynke J., Peng, Garrie, Allegri, Massimo, De Gregori, Manuela, Chelly, Jacques E., Rakel, Barbara A., Aasvang, Eske K., Kehlet, Henrik, Buhre, Wolfgang F.F.A., Bryant, Camron D., Damaj, M. Imad, King, Irah L., Ghasemlou, Nader, Mogil, Jeffrey S., Joosten, Elbert A.J., Diatchenko, Luda, Medische staf Anesthesiologie, Circulatory Health, Parisien, Marc, van Reij, Roel R.I., Khoury, Samar, Koseli, Eda, Karaky, Mohamad, Silva, Jaqueline R., Taheri, Golnar, van den Hoogen, Nynke J., Peng, Garrie, Allegri, Massimo, De Gregori, Manuela, Chelly, Jacques E., Rakel, Barbara A., Aasvang, Eske K., Kehlet, Henrik, Buhre, Wolfgang F.F.A., Bryant, Camron D., Damaj, M. Imad, King, Irah L., Ghasemlou, Nader, Mogil, Jeffrey S., Joosten, Elbert A.J., and Diatchenko, Luda

Published
2024

26. Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia

Author

Verma, Vivek, Drury, Gillian L., Parisien, Marc, Özdağ Acarli, Ayşe N., Al-Aubodah, Tho-Alfakar, Nijnik, Anastasia, wen, Xia, Tugarinov, Nicol, Verner, Maria, Klares, Richie, III, Linton, Alexander, Krock, Emerson, Morado Urbina, Carlos E., Winsvold, Bendik, Fritsche, Lars G., Fors, Egil A., Piccirillo, Ciriaco, Khoutorsky, Arkady, Svensson, Camilla I., Fitzcharles, Mary A., Ingelmo, Pablo M., Bernard, Nicole F., Dupuy, Franck P., Üçeyler, Nurcan, Sommer, Claudia, King, Irah L., Meloto, Carolina B., and Diatchenko, Luda

Published
2021
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29. Satellite glial GPR37L1 regulates maresin and potassium channel signaling for pain control

Author

Bang, Sangsu, primary, Jiang, Changyu, additional, Xu, Jing, additional, Chandra, Sharat, additional, McGinnis, Aidan, additional, Luo, Xin, additional, He, Qianru, additional, Li, Yize, additional, Wang, Zilong, additional, Ao, Xiang, additional, Parisien, Marc, additional, Fernandes de Araujo, Lorenna Oliveira, additional, Esfahan, Sahel Jahangiri, additional, Zhang, Qin, additional, Tonello, Raquel, additional, Berta, Temugin, additional, Diatchenko, Luda, additional, and Ji, Ru-Rong, additional

Published
2023
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30. Sex- and age-specific genetic analysis of chronic back pain

Author

Freidin, Maxim B., Tsepilov, Yakov A., Stanaway, Ian B., Meng, Weihua, Hayward, Caroline, Smith, Blair H., Khoury, Samar, Parisien, Marc, Bortsov, Andrey, Diatchenko, Luda, Børte, Sigrid, Winsvold, Bendik S., Brumpton, Ben M., Zwart, John-Anker, Aulchenko, Yurii S., Suri, Pradeep, and Williams, Frances M.K.

Published
2020
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33. Long-term male-specific chronic pain via telomere- and p53-mediated spinal cord cellular senescence

Author

Muralidharan, Arjun, Sotocinal, Susana G., Yousefpour, Noosha, Akkurt, Nur, Lima, Lucas V., Tansley, Shannon, Parisien, Marc, Wang, Chengyang, Austin, Jean-Sebastien, Ham, Boram, Dutra, Gabrielle M.G.S., Rousseau, Philippe, Maldonado-Bouchard, Sioui, Clark, Teleri, Rosen, Sarah F., Majeed, Mariam R., Silva, Olivia, Nejade, Rachel, Li, Xinyu, Pimentel, Stephania Donayre, Nielsen, Christopher S., Neely, G. Gregory, Autexier, Chantal, Diatchenko, Luda, Ribeiro-da-Silva, Alfredo, and Mogil, Jeffrey S.

Subjects
Complications and side effects, Development and progression, Research, Health aspects, Chronic pain -- Development and progression -- Complications and side effects, Men's health -- Research, Tumor proteins -- Health aspects, Telomeres -- Health aspects, Cell cycle -- Research, Spinal cord injuries -- Development and progression -- Complications and side effects, Medical research, Disease sex factors -- Research, Medicine, Experimental, Men -- Health aspects, Sex factors in disease -- Research
Abstract

Introduction Chronic pain is the most prevalent human health problem, and among the most costly in terms of economic burden and loss of quality of life (1), but remains a [...], Mice with experimental nerve damage can display long-lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53-mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53-positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male-specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male-specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53-specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male-specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.

Published
2022
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34. Genotypic Data in Relational Databases: Efficient Storage and Rapid Retrieval

Author

Lichtenwalter, Ryan N., Zorina-Lichtenwalter, Katerina, Diatchenko, Luda, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Kirikova, Mārīte, editor, Nørvåg, Kjetil, editor, and Papadopoulos, George A., editor

Published
2017
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46. Human Genetic Variability Contributes to Postoperative Morphine Consumption

Author

De Gregori, Manuela, Diatchenko, Luda, Ingelmo, Pablo M., Napolioni, Valerio, Klepstad, Pal, Belfer, Inna, Molinaro, Valeria, Garbin, Giulia, Ranzani, Guglielmina N., Alberio, Giovanni, Normanno, Marco, Lovisari, Federica, Somaini, Marta, Govoni, Stefano, Mura, Elisa, Bugada, Dario, Niebel, Thekla, Zorzetto, Michele, De Gregori, Simona, Molinaro, Mariadelfina, Fanelli, Guido, and Allegri, Massimo

Published
2016
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50. The Quebec Low Back Pain Study: a protocol for an innovative 2-tier provincial cohort

Author

Pagé, Gabrielle M., Lacasse, Anaïs, Beaudet, Nicolas, Choinière, Manon, Deslauriers, Simon, Diatchenko, Luda, Dupuis, Laurent, Grégoire, Stéphanie, Hovey, Richard, Leclair, Erwan, Leonard, Guillaume, Meloto, Carolina B., Montagna, Francesca, Parent, Alexandre, Rainville, Pierre, Roy, Jean-Sébastien, Roy, Mathieu, Ware, Mark A., Wideman, Timothy H., and Stone, Laura S.

Published
2020
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