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2. African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Author

Washington, III, Charles, Dapas, Matthew, Biddanda, Arjun, Magnaye, Kevin M., Aneas, Ivy, Helling, Britney A., Szczesny, Brooke, Boorgula, Meher Preethi, Taub, Margaret A., Kenny, Eimear, Mathias, Rasika A., Barnes, Kathleen C., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gereige, Jessica D., Makhija, Melanie, Gruchalla, Rebecca S., Gill, Michelle A., Liu, Andrew H., Rastogi, Deepa, Busse, William, Gergen, Peter J., Visness, Cynthia M., Gold, Diane R., Hartert, Tina, Johnson, Christine C., Lemanske, Jr., Robert F., Martinez, Fernando D., Miller, Rachel L., Ownby, Dennis, Seroogy, Christine M., Wright, Anne L., Zoratti, Edward M., Bacharier, Leonard B., Kattan, Meyer, O’Connor, George T., Wood, Robert A., Nobrega, Marcelo A., Altman, Matthew C., Jackson, Daniel J., Gern, James E., McKennan, Christopher G., and Ober, Carole

Published
2022
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3. 12,13‐diHOME Promotes Inflammatory Macrophages and Epigenetically Modifies Their Capacity to Respond to Microbes and Allergens.

Author

Lin, Din L., Magnaye, Kevin M., Porsche, Cara E., Levan, Sophia R., Rackaityte, Elze, Özçam, Mustafa, Lynch, Susan V., and Batra, Lalit

Subjects
*IMMUNOLOGIC memory, *IMMUNE response, *ASTHMA in children, *ALLERGENS, *LIPOPOLYSACCHARIDES
Abstract

Elevated infant fecal concentrations of the bacterial‐derived lipid 12,13‐dihydroxy‐9Z‐octadecenoic acid (12,13‐diHOME) increase the risk for childhood atopy and asthma. However, the mechanisms by which this lipid contributes to disease development are largely unknown. We hypothesized that macrophages, which are key to both antimicrobial and antigen responses, are functionally and epigenetically modified by 12,13‐diHOME leading to short‐ and long‐term dysfunction with consequences for both antimicrobial and antigenic responses. Macrophages exposed to 12,13‐diHOME are skewed toward inflammatory IL‐1βhighCD206low cells, a phenomenon that is further amplified in the presence of common microbial‐, aero‐, and food‐allergens. These IL‐1βhighCD206low macrophages also exhibit reduced bacterial phagocytic capacity. In primary immune cell coculture assays involving peanut allergen stimulation, 12,13‐diHOME promotes both IL‐1β and IL‐6 production, memory B cell expansion, and increased IgE production. Exposure to 12,13‐diHOME also induces macrophage chromatin remodeling, specifically diminishing access to interferon‐stimulated response elements resulting in reduced interferon‐regulated gene expression upon bacterial lipopolysaccharide stimulation. Thus 12,13‐diHOME reprograms macrophage effector function, B‐cell interactions and promotes epigenetic modifications that exacerbate inflammatory response to allergens and mutes antimicrobial response along the interferon axis. These observations offer plausible mechanisms by which this lipid promotes early‐life pathogenic microbiome development and innate immune dysfunction associated with childhood allergic sensitization. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

Author

Achten, Niek, Ainsworth, John, Akkerman, Nonna, Anderson, Elizabeth, Anderson, Larry J., Andrews, Howard, Armagost, Elizabeth, Aubuchon, Mary Ann, Bach, Julia, Bacharier, Leonard, Barnes, Kathrine L., Barone, Charles, Bauer, Irma, Beamer, Paloma, Becker, Patrice, Bednarek, Alyssa, Bellemore, Stacey, Bendixsen, Casper G., Biagini Myers, Jocelyn M., Billheimer, Dean, Billstrand, Christine, Birg, Geraldine, Blocki, Shirley, Bloomberg, Gordon, Bobbitt, Kevin, Bochkov, Yury, Bourgeois, Karen, Boushey, Homer, Brockman-Schneider, Rebecca, Brunwasser, Steven M., Budrevich, Richard, Burkle, Jeffrey W., Busse, William, Calatroni, Agustin, Campbell, Janice, Carlson-Dakes, Kirsten, Cassidy-Bushrow, Andrea, Chappell, James D., Chasman, Deborah, Chipps, Teresa M., Chirkova, Tatiana, Cole, Deanna, Connolly, Alexandra, Cootauco, Michelle, Costello, Kaitlin, Couch, Philip, Coull, Brent, Craven, Mark, Crisafi, Gina, Cruikshank, William, Curtsinger, Kristi, Custovic, Adnan, Das, Suman R., DaSilva, Douglas, Datta, Soma, Davidson, Brent, De La Ossa, Lydia, DeVries, Mark, Di, Qian, Dixon, Samara, Donnerbauer, Erin, Dorst, Marian, Doyle, Susan, Dresen, Amy, Dupont, William D., Durrange, Janet, Erickson, Heidi, Evans, Michael D., Ezell, Jerel, Farnham, Leanna, Filardo-Collins, Roxanne, Finazzo, Salvatore, Flege, Zachary, Fleurat, Conner, Floerke, Heather, Floerke, Dorothy, Foss, Terry, Freie, Angela, Frome, Wayne, Fye, Samantha, Gagalis, Lisa, Gammell, Rebecca, Gangnon, Ronald E., Ge, James E., Gebretsadik, Tebeb, Gergen, Peter, Gern, James E., Gibson, Heike, Gjerasi, Edlira, Gold, Diane R., Gonzalez, Nicole, Goodman, Kayla, Gress, Lisa, Grindle, Kristine, Groeschen, Taylor, Hallmark, Brian, Halonen, Marilyn, Hart, Jaime, Hartert, Tina V., Havstad, Suzanne, Heinritz, Patrick, Hensley Alford, Sharon, Herbstman, Julie, Hernandez, Kellie, Hoepner, Lori, Jackson, Daniel J., Jadhao, Samadhan J., Jaffee, Katy, James, Peter, Jezioro, Jacqueline, Jimenez Pescador, Marcia, Johnson, Christine C., Johnson, Tara, Johnson, Camille, Jones, Amelia, Jones, Kyra, Jones, Paul, Jordan, Carolina, Joseph, Christine LM, Kattan, Meyer, Keidel, Kristina, Keifer, Matthew C., Kelley, Rick, Khurana Hershey, Gurgit K., Kim, Haejin, Kloog, Itai, Koepel, Tammy Kronenwetter, Koerkenmeier, Clint, Ladick, Laura, Lamm, Carin, Larkin, Emma, Lederman, Howard, Lee-Parritz, Aviva, Leimenstoll, Stephanie, Lemanske, Jr., Robert F., LeMasters, Grace K., Levin, Albert M., Levine, Jessica, Liu, Xinhua, Liu, Zhouwen, Lopez, Silvia, Lothrop, Nathan, Lovinsky-Desir, Stephanie, Lukacs, Nicholas, Lynch, Susan, Lynch, Christian, Mann, Erik, Martin, Jennifer, Martin, Lisa, Martinez, Fernando D., Matsui, Elizabeth, McCauley, Katherine, Mccollum, Megan, McCullough, Judith, McKennon, Chris G., Meece, Jennifer, Mendonca, Eneida, Mikus, Lance, Miller, Rachel L., Minton, Patricia, Mitchell, Herman, Moon, Vicki, Moore, Paul E., Morgan, Wayne, Morgan, Valerie, Morgan, David, Murrison, Liza, Nicholas, Charlotte, Nicolae, Daniel, Nunez, Adam, O'Connor, George, O'Toole, Sharon, Ober, Carole, Olson, Brent F., Ong, Irene, Osmundson, Sarah, Ownby, Dennis, Pappas, Tressa, Perera, Frederica, Perzanowski, Matthew, Peterson, Edward, Pierce, Marcela, Price-Johnson, Penny, Rajamanickam, Victoria, Ramirez, Judyth, Ray, Kimberly, Renneberg, Megan, Requia, Weeberb, Riley, Kylie, Rivera, Janelle, Rivers, Neisha, Roberg, Kathy, Rogers, Theresa, Rosas-Salazar, Christian, Russell, Pat, Ryan, Patrick H., Sadovsky, Yoel, Salazar, Lisa, Sampson, Hugh, Sandel, Megan, Schoettler, Nathan, Schwartz, Joel, Scott, Dena, Seroogy, Christine M., Sharp, Renee, Shilts, Meghan H., Sigelman, Steve, Singh, Anne Marie, Sitarik, Alexandra, Smartt, Ernestine, Sorkness, Ronald, Sorkness, Christine, Spangenberg, Amber, Sperling, Rhoda, Spies, David, Stern, Debra A., Stoffel, Brandy, Peebles, R. Stokes, Stouffer, Gina, Strauchman Boyer, Cathey, Suddeuth, Caitlin, Tachinardi, Umberto, Tang, Deliang, Tang, Zhengzheng, Tate, Jena, Taylor, William, Tensing, Krista, Tesson, Elizabeth, Thompson, Kathy, Thompson, Emma, Tisler, Christopher, Togias, Alkis, Turi, Kedir, Turner, Victoria, Tuzova, Marina, VanWormer, Jeffrey J., Visness, Cynthia M., Vrtis, Rose, Wahlman, Anthony, Wang, Lena, Wegienka, Ganesa, Wells, Karen, Wentworth-Sheilds, William, Wheatley, Lisa, Whitney, Nitsa, Williams, L. Keoki, Witter, Frank, Wolfe, Christopher, Wood, Robert A., Woodcroft, Kimberley, Woodward, Kim B., Wright, Anne L., Wright, Rosalind, Wu, Pingsheng, Yaeger, Melissa, Yaniv, Perri, Zanobetti, Antonella, Zhang, Shirley, Zook, Patricia, Zoratti, Edward M., McKennan, Chris G, Magnaye, Kevin M, Altman, Matthew C, Washington, Charles, 3rd, Stanhope, Catherine, Naughton, Katherine A, Rosasco, Mario G, Bacharier, Leonard B, Gold, Diane R, Hartert, Tina, Khurana Hershey, Gurjit K, Hogarth, D Kyle, Jackson, Daniel J, Johnson, Christine C, Lemanske, Robert F, Lynch, Susan V, Mendonca, Eneida A, Miller, Rachel L, Naureckas, Edward T, O'Connor, George T, Seroogy, Christine M, White, Steven R, Wood, Robert A, Wright, Anne L, Zoratti, Edward M, Martinez, Fernando D, Nicolae, Dan L, Levin, Albert M, and Gern, James E

Published
2020
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6. Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region

Author

Aneas, Ivy, Decker, Donna C., Howard, Chanie L., Sobreira, Débora R., Sakabe, Noboru J., Blaine, Kelly M., Stein, Michelle M., Hrusch, Cara L., Montefiori, Lindsey E., Tena, Juan, Magnaye, Kevin M., Clay, Selene M., Gern, James E., Jackson, Daniel J., Altman, Matthew C., Naureckas, Edward T., Hogarth, Douglas K., White, Steven R., Gomez-Skarmeta, Jose Luis, Schoetler, Nathan, Ober, Carole, Sperling, Anne I., and Nóbrega, Marcelo A.

Published
2021
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7. Multiple mutant T alleles cause haploinsufficiency of Brachyury and short tails in Manx cats

Author

Buckingham, Kati J, McMillin, Margaret J, Brassil, Margaret M, Shively, Kathryn M, Magnaye, Kevin M, Cortes, Alejandro, Weinmann, Amy S, Lyons, Leslie A, and Bamshad, Michael J

Subjects
Biotechnology, Genetics, 2.1 Biological and endogenous factors, Aetiology, Alleles, Amino Acid Sequence, Animals, Cats, Cell Line, Tumor, Female, Fetal Proteins, Gene Frequency, Genetic Association Studies, Haploinsufficiency, Lod Score, Male, Mice, Molecular Sequence Data, Pedigree, Phenotype, Sequence Analysis, DNA, Sequence Deletion, T-Box Domain Proteins, Tail, Genetics & Heredity
Abstract

Most mammals possess a tail, humans and the Great Apes being notable exceptions. One approach to understanding the mechanisms and evolutionary forces influencing development of a tail is to identify the genetic factors that influence extreme tail length variation within a species. In mice, the Tailless locus has proven to be complex, with evidence of multiple different genes and mutations with pleiotropic effects on tail length, fertility, embryogenesis, male transmission ratio, and meiotic recombination. Five cat breeds have abnormal tail length phenotypes: the American Bobtail, the Manx, the Pixie-Bob, the Kurilian Bobtail, and the Japanese Bobtail. We sequenced the T gene in several independent lineages of Manx cats from both the US and the Isle of Man and identified three 1-bp deletions and one duplication/deletion, each predicted to cause a frameshift that leads to premature termination and truncation of the carboxy terminal end of the Brachyury protein. Ninety-five percent of Manx cats with short-tail phenotypes were heterozygous for T mutations, mutant alleles appeared to be largely lineage-specific, and a maximum LOD score of 6.21 with T was obtained at a recombination fraction (Θ) of 0.00. One mutant T allele was shared with American Bobtails and Pixie-Bobs; both breeds developed more recently in the US. The ability of mutant Brachyury protein to activate transcription of a downstream target was substantially lower than wild-type protein. Collectively, these results suggest that haploinsufficiency of Brachyury is one mechanism underlying variable tail length in domesticated cats.

Published
2013

8. DNA methylation signatures in airway cells from adult children of asthmatic mothers reflect subtypes of severe asthma

Author

Magnaye, Kevin M., primary, Clay, Selene M., additional, Nicodemus-Johnson, Jessie, additional, Naughton, Katherine A., additional, Huffman, Janel, additional, Altman, Matthew C., additional, Jackson, Daniel J., additional, Gern, James E., additional, Hogarth, Douglas K., additional, Naureckas, Edward T., additional, White, Steven R., additional, and Ober, Carole, additional

Published
2022
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9. Additional file 1 of African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

Author

Washington, Charles, Dapas, Matthew, Biddanda, Arjun, Magnaye, Kevin M., Aneas, Ivy, Helling, Britney A., Szczesny, Brooke, Boorgula, Meher Preethi, Taub, Margaret A., Kenny, Eimear, Mathias, Rasika A., Barnes, Kathleen C., Khurana Hershey, Gurjit K., Kercsmar, Carolyn M., Gereige, Jessica D., Makhija, Melanie, Gruchalla, Rebecca S., Gill, Michelle A., Liu, Andrew H., Rastogi, Deepa, Busse, William, Gergen, Peter J., Visness, Cynthia M., Gold, Diane R., Hartert, Tina, Johnson, Christine C., Lemanske, Robert F., Martinez, Fernando D., Miller, Rachel L., Ownby, Dennis, Seroogy, Christine M., Wright, Anne L., Zoratti, Edward M., Bacharier, Leonard B., Kattan, Meyer, O’Connor, George T., Wood, Robert A., Nobrega, Marcelo A., Altman, Matthew C., Jackson, Daniel J., Gern, James E., McKennan, Christopher G., and Ober, Carole

Abstract

Additional file 1. Contains Supplementary Methods, Supplementary Tables (Table S1-10), and Supplementary Figures (Fig. S1-14), and corresponding references. Supplementary Methods. Descriptions of Populations. Building Consensus Sequences in the Critical Region. Table S1. Characteristics of the APIC and URECA Cohorts. Table S2. Predicted Haplotypes in CREW. Table S3. Haplotype Frequencies in Whole Genome Sequences. Table S4. Worldwide Frequencies of African-specific SNPs. Table S5. cis-eQTL Results for SNPs in or near GSDMA. Table S6. ENCODE Cell Lines and DNAse Clustering at pcHi-C Region. Table S7. pcHi-C Target Genes for African-specific Variants in Airway Epithelial Cells. Table S8. pcHi-C Target Genes for African-specific Variants in Airway Immune Cells. Table S9. Quantitative Trait Association Results in the APIC and URECA Cohorts. Table S10. African American Adult Asthmatics by Severity and Genotype. Figure S1. Overview of Study Design. Figure S2. ChromoPainter Analysis. Figure S3. ChromoPainter Visualization of Haplotype Breakpoints. Figure S4. ChromoPainter Display of the 17q12-q21 Region in Haplotype 4 Homozygotes. Figure S5. Ancestry PCA plots for APIC and URECA Children. Figure S6. eQTL Box Plots of rs28623237 Genotype and GSDMA Expression in CAAPA2. Figure S7. LD Plot of African-specific Variants and SNPs in or near GSDMA. Figure S8. eQTL Box Plots of rs113282230 Genotype and GSDMA Expression Conditioned on GSDMA SNPs. Figure S9. eQTL Violin Plots of rs235480 and rs1132828830 Genotypes on GSDMA and GSDMB Expression. Figure S10. LD Plot of the African-specific Variants and SNPs in the Core Region of The 17q12-q21 Locus. Figure S11. Chromatin Annotations in the Region Encoding the African-specific SNPs in ENCODE Cell Lines. Figure S12. eGenes for rs113282230 in Immune Cells. Figure S13. pcHi-C Data for rs113282230 in Immune Cells. Figure S14. Rs113282230 Genotype Effect on Asthma Prevalence by rs2305480 AA And GG Genotypes in APIC and URECA.

Published
2022
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11. Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region

Author

National Institutes of Health (US), Aneas, Ivy, Decker, Donna C., Howard, Chanie L., Sobreira, Débora R., Sakabe, Noboru J., Blaine, Kelly M., Stein, Michelle M., Hrusch, Cara L., Montefiori, Lindsey E., Tena, Juan J., Magnaye, Kevin M., Clay, Selene M., Gern, James E., Jackson, Daniel J., Altman, Matthew C., Naureckas, Edward T., Hogarth, Douglas K., White, Steven R., Gómez-Skarmeta, José Luis, Schoetler, Nathan, Ober, Carole, Sperling, Anne I., Nóbrega, Marcelo A., National Institutes of Health (US), Aneas, Ivy, Decker, Donna C., Howard, Chanie L., Sobreira, Débora R., Sakabe, Noboru J., Blaine, Kelly M., Stein, Michelle M., Hrusch, Cara L., Montefiori, Lindsey E., Tena, Juan J., Magnaye, Kevin M., Clay, Selene M., Gern, James E., Jackson, Daniel J., Altman, Matthew C., Naureckas, Edward T., Hogarth, Douglas K., White, Steven R., Gómez-Skarmeta, José Luis, Schoetler, Nathan, Ober, Carole, Sperling, Anne I., and Nóbrega, Marcelo A.

Abstract

Genome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as an enhancer-blocking element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that the asthma-associated single nucleotide polymorphism (SNP) rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a mechanism through which a regulatory SNP contributes to genetic risk of asthma.

Published
2021

14. Asthma-associated variants induce IL33 differential expression through a novel regulatory region

Author

Aneas, Ivy, primary, Decker, Donna C., additional, Howard, Chanie L., additional, Sobreira, Débora R., additional, Sakabe, Noboru J., additional, Blaine, Kelly M., additional, Stein, Michelle M., additional, Hrusch, Cara L., additional, Montefiori, Lindsey E., additional, Tena, Juan, additional, Magnaye, Kevin M., additional, Clay, Selene M., additional, Gern, James E., additional, Jackson, Daniel J., additional, Altman, Matthew C., additional, Naureckas, Edward T., additional, Hogarth, Douglas K., additional, White, Steven R., additional, Gomez-Skarmeta, Jose Luis, additional, Schoetler, Nathan, additional, Ober, Carole, additional, Sperling, Anne I., additional, and Nobrega, Marcelo A., additional

Published
2020
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15. Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

Author

Ober, Carole, primary, McKennan, Chris G, additional, Magnaye, Kevin M, additional, Altman, Matthew C, additional, Washington, Charles, additional, Stanhope, Catherine, additional, Naughton, Katherine A, additional, Rosasco, Mario G, additional, Bacharier, Leonard B, additional, Billheimer, Dean, additional, Gold, Diane R, additional, Gress, Lisa, additional, Hartert, Tina, additional, Havstad, Suzanne, additional, Khurana Hershey, Gurjit K, additional, Hallmark, Brian, additional, Hogarth, D Kyle, additional, Jackson, Daniel J, additional, Johnson, Christine C, additional, Kattan, Meyer, additional, Lemanske, Robert F, additional, Lynch, Susan V, additional, Mendonca, Eneida A, additional, Miller, Rachel L, additional, Naureckas, Edward T, additional, O'Connor, George T, additional, Seroogy, Christine M, additional, Wegienka, Ganesa, additional, White, Steven R, additional, Wood, Robert A, additional, Wright, Anne L, additional, Zoratti, Edward M, additional, Martinez, Fernando D, additional, Ownby, Dennis, additional, Nicolae, Dan L, additional, Levin, Albert M, additional, Gern, James E, additional, Achten, Niek, additional, Ainsworth, John, additional, Akkerman, Nonna, additional, Anderson, Elizabeth, additional, Anderson, Larry J., additional, Andrews, Howard, additional, Armagost, Elizabeth, additional, Aubuchon, Mary Ann, additional, Bach, Julia, additional, Bacharier, Leonard, additional, Barnes, Kathrine L., additional, Barone, Charles, additional, Bauer, Irma, additional, Beamer, Paloma, additional, Becker, Patrice, additional, Bednarek, Alyssa, additional, Bellemore, Stacey, additional, Bendixsen, Casper G., additional, Biagini Myers, Jocelyn M., additional, Billstrand, Christine, additional, Birg, Geraldine, additional, Blocki, Shirley, additional, Bloomberg, Gordon, additional, Bobbitt, Kevin, additional, Bochkov, Yury, additional, Bourgeois, Karen, additional, Boushey, Homer, additional, Brockman-Schneider, Rebecca, additional, Brunwasser, Steven M., additional, Budrevich, Richard, additional, Burkle, Jeffrey W., additional, Busse, William, additional, Calatroni, Agustin, additional, Campbell, Janice, additional, Carlson-Dakes, Kirsten, additional, Cassidy-Bushrow, Andrea, additional, Chappell, James D., additional, Chasman, Deborah, additional, Chipps, Teresa M., additional, Chirkova, Tatiana, additional, Cole, Deanna, additional, Connolly, Alexandra, additional, Cootauco, Michelle, additional, Costello, Kaitlin, additional, Couch, Philip, additional, Coull, Brent, additional, Craven, Mark, additional, Crisafi, Gina, additional, Cruikshank, William, additional, Curtsinger, Kristi, additional, Custovic, Adnan, additional, Das, Suman R., additional, DaSilva, Douglas, additional, Datta, Soma, additional, Davidson, Brent, additional, De La Ossa, Lydia, additional, DeVries, Mark, additional, Di, Qian, additional, Dixon, Samara, additional, Donnerbauer, Erin, additional, Dorst, Marian, additional, Doyle, Susan, additional, Dresen, Amy, additional, Dupont, William D., additional, Durrange, Janet, additional, Erickson, Heidi, additional, Evans, Michael D., additional, Ezell, Jerel, additional, Farnham, Leanna, additional, Filardo-Collins, Roxanne, additional, Finazzo, Salvatore, additional, Flege, Zachary, additional, Fleurat, Conner, additional, Floerke, Heather, additional, Floerke, Dorothy, additional, Foss, Terry, additional, Freie, Angela, additional, Frome, Wayne, additional, Fye, Samantha, additional, Gagalis, Lisa, additional, Gammell, Rebecca, additional, Gangnon, Ronald E., additional, Ge, James E., additional, Gebretsadik, Tebeb, additional, Gergen, Peter, additional, Gern, James E., additional, Gibson, Heike, additional, Gjerasi, Edlira, additional, Gold, Diane R., additional, Gonzalez, Nicole, additional, Goodman, Kayla, additional, Grindle, Kristine, additional, Groeschen, Taylor, additional, Halonen, Marilyn, additional, Hart, Jaime, additional, Hartert, Tina V., additional, Heinritz, Patrick, additional, Hensley Alford, Sharon, additional, Herbstman, Julie, additional, Hernandez, Kellie, additional, Hoepner, Lori, additional, Jackson, Daniel J., additional, Jadhao, Samadhan J., additional, Jaffee, Katy, additional, James, Peter, additional, Jezioro, Jacqueline, additional, Jimenez Pescador, Marcia, additional, Johnson, Christine C., additional, Johnson, Tara, additional, Johnson, Camille, additional, Jones, Amelia, additional, Jones, Kyra, additional, Jones, Paul, additional, Jordan, Carolina, additional, Joseph, Christine LM, additional, Keidel, Kristina, additional, Keifer, Matthew C., additional, Kelley, Rick, additional, Khurana Hershey, Gurgit K., additional, Kim, Haejin, additional, Kloog, Itai, additional, Koepel, Tammy Kronenwetter, additional, Koerkenmeier, Clint, additional, Ladick, Laura, additional, Lamm, Carin, additional, Larkin, Emma, additional, Lederman, Howard, additional, Lee-Parritz, Aviva, additional, Leimenstoll, Stephanie, additional, Lemanske, Jr., Robert F., additional, LeMasters, Grace K., additional, Levin, Albert M., additional, Levine, Jessica, additional, Liu, Xinhua, additional, Liu, Zhouwen, additional, Lopez, Silvia, additional, Lothrop, Nathan, additional, Lovinsky-Desir, Stephanie, additional, Lukacs, Nicholas, additional, Lynch, Susan, additional, Lynch, Christian, additional, Mann, Erik, additional, Martin, Jennifer, additional, Martin, Lisa, additional, Martinez, Fernando D., additional, Matsui, Elizabeth, additional, McCauley, Katherine, additional, Mccollum, Megan, additional, McCullough, Judith, additional, McKennon, Chris G., additional, Meece, Jennifer, additional, Mendonca, Eneida, additional, Mikus, Lance, additional, Miller, Rachel L., additional, Minton, Patricia, additional, Mitchell, Herman, additional, Moon, Vicki, additional, Moore, Paul E., additional, Morgan, Wayne, additional, Morgan, Valerie, additional, Morgan, David, additional, Murrison, Liza, additional, Nicholas, Charlotte, additional, Nicolae, Daniel, additional, Nunez, Adam, additional, O'Connor, George, additional, O'Toole, Sharon, additional, Ober, Carole, additional, Olson, Brent F., additional, Ong, Irene, additional, Osmundson, Sarah, additional, Pappas, Tressa, additional, Perera, Frederica, additional, Perzanowski, Matthew, additional, Peterson, Edward, additional, Pierce, Marcela, additional, Price-Johnson, Penny, additional, Rajamanickam, Victoria, additional, Ramirez, Judyth, additional, Ray, Kimberly, additional, Renneberg, Megan, additional, Requia, Weeberb, additional, Riley, Kylie, additional, Rivera, Janelle, additional, Rivers, Neisha, additional, Roberg, Kathy, additional, Rogers, Theresa, additional, Rosas-Salazar, Christian, additional, Russell, Pat, additional, Ryan, Patrick H., additional, Sadovsky, Yoel, additional, Salazar, Lisa, additional, Sampson, Hugh, additional, Sandel, Megan, additional, Schoettler, Nathan, additional, Schwartz, Joel, additional, Scott, Dena, additional, Seroogy, Christine M., additional, Sharp, Renee, additional, Shilts, Meghan H., additional, Sigelman, Steve, additional, Singh, Anne Marie, additional, Sitarik, Alexandra, additional, Smartt, Ernestine, additional, Sorkness, Ronald, additional, Sorkness, Christine, additional, Spangenberg, Amber, additional, Sperling, Rhoda, additional, Spies, David, additional, Stern, Debra A., additional, Stoffel, Brandy, additional, Peebles, R. Stokes, additional, Stouffer, Gina, additional, Strauchman Boyer, Cathey, additional, Suddeuth, Caitlin, additional, Tachinardi, Umberto, additional, Tang, Deliang, additional, Tang, Zhengzheng, additional, Tate, Jena, additional, Taylor, William, additional, Tensing, Krista, additional, Tesson, Elizabeth, additional, Thompson, Kathy, additional, Thompson, Emma, additional, Tisler, Christopher, additional, Togias, Alkis, additional, Turi, Kedir, additional, Turner, Victoria, additional, Tuzova, Marina, additional, VanWormer, Jeffrey J., additional, Visness, Cynthia M., additional, Vrtis, Rose, additional, Wahlman, Anthony, additional, Wang, Lena, additional, Wells, Karen, additional, Wentworth-Sheilds, William, additional, Wheatley, Lisa, additional, Whitney, Nitsa, additional, Williams, L. Keoki, additional, Witter, Frank, additional, Wolfe, Christopher, additional, Wood, Robert A., additional, Woodcroft, Kimberley, additional, Woodward, Kim B., additional, Wright, Anne L., additional, Wright, Rosalind, additional, Wu, Pingsheng, additional, Yaeger, Melissa, additional, Yaniv, Perri, additional, Zanobetti, Antonella, additional, Zhang, Shirley, additional, Zook, Patricia, additional, and Zoratti, Edward M., additional

Published
2020
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16. A decade of research on the 17q12-21 asthma locus:Piecing together the puzzle

Author

Stein, Michelle M., Thompson, Emma E., Schoettler, Nathan, Helling, Britney A., Magnaye, Kevin M., Stanhope, Catherine, Igartua, Catherine, Morin, Andréanne, Washington, Charles, Nicolae, Dan, Bønnelykke, Klaus, Ober, Carole, Stein, Michelle M., Thompson, Emma E., Schoettler, Nathan, Helling, Britney A., Magnaye, Kevin M., Stanhope, Catherine, Igartua, Catherine, Morin, Andréanne, Washington, Charles, Nicolae, Dan, Bønnelykke, Klaus, and Ober, Carole

Abstract

Chromosome 17q12-21 remains the most highly replicated and significant asthma locus. Genotypes in the core region defined by the first genome-wide association study correlate with expression of 2 genes, ORM1-like 3 (ORMDL3) and gasdermin B (GSDMB), making these prime candidate asthma genes, although recent studies have implicated gasdermin A (GSDMA) distal to and post-GPI attachment to proteins 3 (PGAP3) proximal to the core region as independent loci. We review 10 years of studies on the 17q12-21 locus and suggest that genotype-specific risks for asthma at the proximal and distal loci are not specific to early-onset asthma and mediated by PGAP3, ORMDL3, and/or GSDMA expression. We propose that the weak and inconsistent associations of 17q single nucleotide polymorphisms with asthma in African Americans is due to the high frequency of some 17q alleles, the breakdown of linkage disequilibrium on African-derived chromosomes, and possibly different early-life asthma endotypes in these children. Finally, the inconsistent association between asthma and gene expression levels in blood or lung cells from older children and adults suggests that genotype effects may mediate asthma risk or protection during critical developmental windows and/or in response to relevant exposures in early life. Thus studies of young children and ethnically diverse populations are required to fully understand the relationship between genotype and asthma phenotype and the gene regulatory architecture at this locus.

Published
2018

18. A decade of research on the 17q12-21 asthma locus: Piecing together the puzzle

Author

Stein, Michelle M., primary, Thompson, Emma E., additional, Schoettler, Nathan, additional, Helling, Britney A., additional, Magnaye, Kevin M., additional, Stanhope, Catherine, additional, Igartua, Catherine, additional, Morin, Andréanne, additional, Washington, Charles, additional, Nicolae, Dan, additional, Bønnelykke, Klaus, additional, and Ober, Carole, additional

Published
2018
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