Citations 2
An APOE *4-Informed Genomic Atlas of the X Chromosome in Alzheimer’s Disease
Cook, Noah , Zeng, Youjie , Yang, Chenyu , Jiang, Zhiwen , Wang, Ting‐Chen , Guen, Yann Le , Cody, Karly Alex , Johnson, Matthew, Zhang, Rui, Merritt, Victoria C. , Hauger, Richard L. , Program, the VA Million Veteran, FinnGen, Koran, Mary Ellen, Mormino, Elizabeth C. , Gordon, Brian , DeCasien, Alex, Andrews, Shea J. , Logue, Mark, Greicius, Michael D. , Le Guen, Yann , Cody, Karly A , Koran, Mary Ellen , Gordon, Brian A , Andrews, Shea , Dumitrescu, Logan , Archer, Derek , Seto, Mabel , Pottier, Cyril , Cruchaga, Carlos , Sherva, Richard , Logue, Mark W. , Napolioni, Valerio , Belloy, Michael E , Cook, Noah , Zeng, Youjie , Yang, Chenyu , Zhang, Rui, Merritt, Victoria C. , Hauger, Richard L. , Koran, Mary Ellen I. , Mormino, Elizabeth C. , DeCasien, Alex R. , Dumitrescu, Logan , Archer, Derek B. , Hohman, Timothy J. , Belloy, Michaël E.
No container title available | May 6, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract The genetic contributions of the X chromosome to Alzheimer’s disease (AD) remain poorly understood yet are expected to importantly shape sex differences in AD. We therefore performed large-scale X-chromosome-wide association studies (N=1,240,451), evaluating differential risk due to sex, APOE *4, and escape from X-chromosome inactivation, finding most X-linked loci appear relevant to female-biased AD etiology. In evaluating genetic pleiotropy with hormonal, lipid, and brain imaging traits, we discovered X-linked AD loci converged on white matter traits, particularly in the anterior corona radiata and splenium of the corpus callosum. Through brain-centric functional genomics analyses, we then nominated candidate causal genes, including 5 that appeared highly robust. Notably, we found the escape gene RBBP7 decreases AD risk in APOE *4 carriers likely through higher expression in excitatory neurons to counter tau-related neurodegeneration. Altogether, we provide an atlas of sex and APOE *4-informed candidate X-linked AD risk loci, genes, and mechanisms that will guide future studies.
Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm
Bell, Edward F. , Barbara, T. , Greenberg, Rachel G. , Stoll, Barbara J. , DeMauro, Sara B. , Harmon, Heidi M. , Hintz, Susan R. , Das, Abhik , Puopolo, Karen M. , Bailey, Kirstin J., Biasini, Fred J., Chopko, Stephanie A., Collins, Monica V., Cosby, Shirley S., Johnston, Kristen C. , Moses, Mary Beth, Nelson, Kathleen G., Patterson, Cryshelle S., Peralta-Carcelén, Myriam , Phillips, Vivien A., Preskitt, Julie , Rector, Richard V., Whitley, Sally, Alksninis, Barbara, Bishop, Carmena, Burke, Robert T., Caskey, Melinda, Hensman, Angelita M. , Hoffman, Laurie , Johnson, Katharine, Keszler, Mary Lenore, Knoll, Andrea M., Lamberson, Vita, Laptook, Abbot R. , Leach, Theresa M., Little, Emilee, McGowan, Elizabeth C., Pierre, Lucille St., Stephens, Bonnie E., Ventura, Suzy, Vieira, Elisa , Vohr, Betty R. , Coleman, Kelly R., Guilford, Stephanie , Hartley-McAndrew, Michelle, Li, Emily, Reynolds, Anne Marie , Sacilowski, Michael G., Williams, Ashley, Zorn, William, Bhola, Monika , Fanaroff, Avroy A., Friedman, Harriet, Newman, Nancy S., Siner, Bonnie S., Walsh, Michele C. , Wilson-Costello, Deanne E. , Yalcinkaya, Gulgun, Caplan, Michael S. , Beiersdorfer, Traci , Bridges, Kate, Cahill, Tanya E., Donovan, Edward F., Dudley, Juanita , Fischer, Estelle E., Gratton, Teresa L., Grisby, Cathy, Hayes, Devan, Hessling, Jody, Jackson, Lenora, Kallapur, Suhas G. , Kirker, Kristin, Merhar, Stephanie L. , Mincey, Holly L., Muthig, Greg, Poindexter, Brenda B. , Schibler, Kurt, Stacey, Sara, Steichen, Jean J., Tepe, Stacey, Thompson, Julia, Mersmann, Marcia Worley, Wuertz, Sandra, Polin, Richard A. , Adams, Sally S., Leon, Maria Magdalena, Eubanks, Frances, Guzman, Alicia, Hensley, Gaynelle, Heyne, Elizabeth T., Heyne, Roy J. , Hickman, Jackie F., Lee, Lizette E. , Leps, Melissa H., Madden, Linda A., McDougald, E. Rebecca, Miller, Nancy A., Morgan, Janet S., Pavageau, Lara, Salhab, Walid A., Sepulveda, Pollieanna , Boatman, Catherine Twell, Vasil, Diana M., Waterbury, Jillian, Wyckoff, Myra H. , Ashley, Patricia L., Auten, Kathy J., Cotten, C. Michael , Finkle, Joanne, Fisher, Kimberley A. , Goldberg, Ronald N., Goldstein, Ricki F., Grimes, Sandra, Gustafson, Kathryn E. , Lohmeyer, Melody B., Malcolm, William , Adams‐Chapman, Ira , Blackwelder, Ann M., Bottcher, Diane I., Carlton, David P., Carter, Sheena L., Hale, Ellen C., Kendrick-Allwood, Salathiel, Laursen, Judith, Loggins, Yvonne, Mackie, Colleen, LaRossa, Maureen Mulligan, Sanders, Amy , Seabrook, Irma, Smikle, Gloria V., Wineski, Lynn, Akpa, Esther, Alaniz, Nora I., Allain, Elizabeth, Arldt-McAlister, Julie, Bradt, Pamela J., Burson, Katrina, Dieterich, Susan, Duncan, Andrea F. , Eason, Elizabeth, Evans, Patricia W., Harris, Beverly Foley, Franco, Claudia I., Garcia, Carmen, Hall, Donna J., Jiménez, Margarita, John, Janice , Jones, Patrick M., Kennedy, Kathleen A. , Siddiki, Saba Khan, Lillie, Layne M., Major-Kincade, Terri L., Martin, Sara C., McDavid, Georgia E., McKee, Shannon L. , Morris, Brenda H., Orekoya, Patricia Ann, Pedrozza, Claudia, Perez, Carrie M., Tate, Patti L. Pierce, Reddoch, Stacey, Rodgers, Shawna, Simmons, Maegan C., Sperry, Daniel K., Stephens, Emily K. , Tyson, Jon E., Whitely, Laura L., Wright, Sharon L., Dusick, Anna M., Gunn, Susan, Hamer, Faithe, Herron, Dianne E., Hines, Abbey C. , Joyce, Jeffery, Lemons, James A., Lytle, Carolyn, Miller, Lucy , Minnich, Heike M., Papile, L.A., Richard, Leslie, Smiley, Lucy, Sokol, Gregory M. , Wilson, Leslie Dawn, Acarregui, Michael J., Colaizy, Tarah T. , Eastman, Diane L., Goeke, Claire A., Johnson, Karen, Krutzfield, Nancy J., Schmelzel, Mendi L., Walker, Jacky R., Bass, Donia B., Ellsbury, Dan L., Tud, Tracy L., Bauer, Charles R., Duara, Shahnaz , Everett‐Thomas, Ruth , Fajardo-Hiriart, Sylvia, Eguaras, Silvia M. Frade, Garcia, Andrea, Berkovits, Michelle Harwood, Pierre, Helina, Riguard, Arielle, Stoerger, Alexandra, Gaetano, Lisa, Gauldin, Cheri, Holmes, Anne, Johnson, Kathy, Kilbride, Howard W. , Pallotto, Eugenia K. , Parimi, Prabhu S., Scott, Allison, Truog, William E., Besner, Gail E. , Clark, Erna, Gutentag, Julie, Jadcherla, Sudarshan R. , Luzader, Patricia, Park, Courtney, Shadd, Julie C., Stein, Melanie, Sullivan, Margaret, Bremer, Andrew A. , Higgins, Rosemary D. , Archer, Stephanie Wilson , Abbasi, Soraya, Bernbaum, Judy, Catts, Christine, Chaudhary, Aasma S. , Cucinotta, Dara M., Eichenwald, Eric C. , Gerdes, Marsha , Ghavam, Sarvin, Hurt, Hallam, Snyder, Jonathan, Vangala, Sarith, Ziolkowski, Kristina, Johnson, Julie Babish, Binion, Kyle, Bowman, Melissa, Burnell, Erica, D’Angio, Carl T., Fallone, Caitlin, Farooq, Osman , Guillet, Ronnie , Horihan, Cassandra A., Hunn, Julianne, Hust, Diane, Jensen, Rosemary L., Jones, Rachel , Kachelmeyer, Jennifer , Kushner, Emily, Maffett, Deanna, McKee, Kimberly G., Merzbach, Joan, Myers, Gary J. , Orme, Constance, Phelps, Dale L. , Dm, Prinzing, Reubens, Linda J., Rochez, Daisy, Rowan, Mary, Sabaratnam, Premini, Scorsone, Ann Marie, Wadkins, Holly I.M., Yost, Kelley, Zwetsch, Lauren, Gabrio, Jenna, Hastings, Betty K., LeBlond, David, Auman, Jeanette O’Donnell , Huitema, Carolyn M. Petrie , Poole, W. Kenneth, Wallace, Dennis, Zaterka-Baxter, Kristin M. , Baack, Michelle , Broadbent, Megan, Elenkiwich, Chelsey, Henning, Megan M., Hogden, Laurie A., Adams, Marian M. , Bahmani, Dona, Ball, M. Bethany , Bentley, Barbara, Bruno, Elizabeth F., Chock, Valerie Y. , Davis, Alexis S. , DeAnda, Maria Elena, DeBattista, Anne M., Earhart, Beth, Huffman, Lynne C. , Ismael, Magdy, Kohn, Jean G., Krueger, Casey E., Lee-Ancajas, Julie C., Lowe, Janice, Lucash, Ryan E., Palmquist, Andrew W., Patel, Jessica, Proud, Melinda S., Reichert, Elizabeth N., Sivakumar, Dharshi, John, Nicholas H. St., Stevenson, David K. , Meurs, Krisa P. Van , Wager, Natalie, Williams, R. Jordan , Weiss, Hali E., Brussa, Ana K. , Church, Paige , Fiascone, John M., Frantz, Ivan D. , Furey, Anne, Kurfiss, Anne, MacKinnon, Brenda L., McGowan, Elisabeth C. , Nylen, Ellen, Sibley, Cecelia, Chanlaw, Teresa , Devaskar, Uday, Garg, Meena, Geller, Rachel , Purdy, Isabell B., Arnell, Kathy, Demetrio, Clarence, Finer, Neil N., Fuller, Martha G. , Henderson, Christopher, Kaegi, David, Rasmussen, Maynard R., Rich, Wade , Vaucher, Yvonne E. , Wozniak, Paul R., Bernhardt, Janice, Bose, Carl , Bose, Gennie, Clark, Cynthia L., Warner, Diane, Wereszczak, Janice, Lacy, Conra Backstrom, Fuller, Janell, Hanson, Mary, Hartenberger, Carol H., Kuan, Elizabeth, Lowe, Jean, Ohls, Robin K. , Beauman, Sandra Sundquist , Thomson, Rebecca A., Watterberg, Kristi L. , Carlson, Martha, Christensen, Mary, Wiggins, Stephanie A., Baker, Shawna, Baserga, Mariana , Bird, Karie, Burnett, Jill, Christensen, Susan, Bledsoe, Laura Cole, Cunningham, Sean D. , Davis, Brandy, Elmont, Jennifer O., Faix, Roger G., Hall, Becky, Jensen, Erika R., Jensen, Jennifer J., Jordan, Jamie, Loertscher, Manndi C., Marchant, Trisha, Maxson, Earl, McGrath, Kandace M., Minton, Stephen D., Morshedzadeh, Galina, Osborne, Karen A., Parry, Dilys M. , Rau, Carrie A., Reich, Brixen A., Schaefer, Susan T., Sheffield, Mark J., Spencer, Cynthia, Steffen, Michael, Stout, Kelly, Stuart, Ashley L., Tice, Katherine, Weaver-Lewis, Kimberlee, Winter, Sarah , Woodbury, Kathryn D., Yoder, Bradley A. , Zanetti, Karen, Chiu, Korinne, Dillard, Robert G., Allred, Deborah Evans, Goldstein, Donald J., Halfond, Raquel, Jackson, Barbara G., O’Shea, T. Michael , Peters, Nancy, Peterson, Carroll, Waldrep, Ellen, Washburn, Lisa K. , Welch, Cherrie D. , Morris, Melissa Whalen, Hounshell, Gail, Kicklighter, Stephen D. , Rhodes-Ryan, Ginger, Abramczyk, Katherine, Agarwal, Prashant , Bajaj, Monika , Bara, Rebecca, Billian, Elizabeth, Chawla, Sanjay , Childs, Kirsten, Jesus, Lilia C. De, Driscoll, D., February, Melissa, Goldston, Laura A., Muran, Geraldine, Natarajan, Girija , Pappas, Athina, Prentice, Jeannette E., Shankaran, Seetha , Sood, Beena G. , White, Diane F., Woldt, Eunice, Butler, Christine G., Cervone, Patricia, Ehrenkranz, Richard A., Gettner, Patricia, Greisman, Sheila, Jacobs, Harris C., Konstantino, Monica, Poulsen, JoAnn, Romano, Elaine, Taft, Janet, Brumbaugh, Jane E. , Das, Abhik , Baack, Michelle L , Ambalavanan, Namasivayam , Carlo, Waldemar A. , Keszler, Martin , Oh, William, Watson, Victoria E. , Lakshminrusimha, Satyan , Hibbs, Anna Maria , Payne, Allison H. , Alexander, Barbara D. , Jobe, Alan Hall , Yolton, Kimberly , Brion, Luc P. , Chen, Lijun , Leon, Maria M. De, Miller, Nancy A., Rosenfeld, Charles R. , Sánchez, Pablo J. , Patel, Ravi M. , Dempsey, Allison G. , Green, Charles E. , Khan, Amir M , Lis, Anna E. , Martin, Karen , Dagle, John M. , Klein, Jonathan M. , Widness, John A. , Calejo, Maria, Fortney, Christine A. , Maitre, Nathalie L. , Nelin, Leif Daniel , Parikh, Nehal A. , Cook, Noah , Kirpalani, Haresh Murli , Mancini, Toni, Schmidt, Barbara Kristina , Vangala, Saritha, Kent, Alison , Sabaratnam, Premini , Bann, Carla , Crawford, Margaret M. , Gantz, Marie G. , Leblond, David, Newman, Jamie E. , Taylor, Heather Lee , Henderson, Christopher, Laughon, Matthew Maxwell , DuPont, Tara L. , Barks, John , Sarkar, Subrata , Parry, D. Melody, Spencer, Cynthia, Steffen, Michael, White, Donna, Johnson, Mary E. , Panaitescu, Bogdan , Williams, Joanne W.
JAMA Network Open | December 8, 2022 | Volume: 5 | Issue: 12 | Pages: e2245826
10.1001/jamanetworkopen.2022.45826
ImportanceLate-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm.ObjectiveTo report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age.Design, Setting, and ParticipantsThis cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks’ gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers.ExposuresCulture-confirmed LOM.Main Outcomes and MeasuresIncidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021).ResultsAmong 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 (P < .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P < .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P < .001) and among those with culture-confirmed LOS (23%-79%, P < .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus, 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection.Conclusions and RelevanceIn this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.