Citations 2
TMEM161B regulates cerebral cortical gyration, Sonic Hedgehog signaling, and ciliary structure in the developing central nervous system
Akula, Shyam K. , Marciano, Jack H. , Lim, Youngshin , Exposito-Alonso, David , Hylton, Norma K. , Hwang, Grace H. , Neil, Jennifer E., Dominado, Nicole , Bunton-Stasyshyn, Rosie , Song, Janet , Talukdar, Maya , Schmid, Aloisia, Teboul, Lydia , Mo, Alisa , Finander, Benjamin , Beck, Samantha G., Yeh, Rebecca C., Otani, Aoi, Qian, Xuyu , DeGennaro, Ellen M. , Alkuraya, Fowzan S. , Maddirevula, Sateesh , Cascino, Gregory D. , Network, Undiagnosed Diseases, Burrage, Lindsay C. , Rosenfield, Jill A., Ketkar, Shamika , Clark, Gary, Bacino, Carlos A. , Lewis, Richard A. , Segal, Rosalind A. , Bazán, J. Fernando , Smith, K. A. , Golden, Jeffrey A. , Cho, Ginam , Walsh, Christopher A. , Alejandro, Mercedes E., Ashley, Euan A. , Baker, Eva H. , Balasubramanyam, Ashok , Barseghyan, Hayk , Batzli, Gabriel F., Bernstein, Jonathan A. , Bican, Anna, Bick, David , Birch, Camille L., Boone, Braden, Bostwick, Bret L. , Briere, Lauren C. , Brokamp, Elly , Brush, Matthew , Chen, Shan , Coakley, Terra R., Cobban, Laurel A., Colley, Heather A., Cooper, Cynthia M. , Craigen, William J., D’Souza, Precilla , Davids, Mariska, Davidson, Jean M. , Dayal, Jyoti G. , Dell’Angelica, Esteban C., Dhar, Shweta U. , Dipple, Katrina M. , Dorrani, Naghmeh, Dorset, Daniel C., Douglas, Jessica, Draper, David D., Dries, Annika M., Eckstein, David J. , Emrick, Lisa , Eng, Christine M. , Enns, Gregory M. , Eskin, Ascia , Esteves, Cecilia, Estwick, Tyra, Fernández, Liliana, Fogel, Brent L. , Friedman, Noah D., Gahl, William A. , Godfrey, Rena A., Goldstein, David B. , Gould, Sarah E., Groden, Catherine, Hamid, Rizwan , Hanchard, Neil A. , High, Frances A. , Hom, Jason , Howerton, Ellen M. , Jamal, Fariha , Jiang, Yong‐hui , Johnston, Jean M., Karaviti, Lefkothea , Kelley, Emily G., Koeller, David M. , Kohane, Isaac S. , Kohler, Jennefer N., Korrick, Susan , Kozuira, Mary, Krasnewich, Donna M., Krier, Joel B. , Lau, C. Christopher, Lazar, Jozef, LeBlanc, Kimberly , Lee, Brendan , Lee, Hane , Lewis, Richard A., Loscalzo, Joseph, Maas, Richard L., MacRae, Calum A. , Maduro, Valerie V. , Majcherska, Marta M., Malicdan, May Christine V. , Mamounas, Laura A., Manolio, Teri A. , Markello, Thomas C. , Martín, Martín G., Marwaha, Shruti , May, Thomas , McConkie‐Rosell, Allyn , McCormack, Colleen E., McCray, Alexa T. , Merker, Jason D. , Moretti, Paolo , Morimoto, Marie , Murdock, David R. , Muzny, Donna M., Nehrebecky, Michele, Nelson, Stan F., Newberry, J. Scott, Newman, John H. , Nicholas, Sarah K. , Novacic, Donna, Orengo, James P. , Pallais, J. Carl , Palmer, Christina G.S. , Papp, Jeanette C. , Parker, Neil H., Peña, Loren D.M. , Phillips, John A., Potocki, Lorraine , Pusey, Barbara N., Renteria, Genecee, Rives, Lynette, Robertson, Amy K., Rodan, Lance H. , Sampson, Jacinda B. , Samson, Susan L. , Schoch, Kelly, Shakachite, Lisa, Sharma, Prashant , Shashi, Vandana , Signer, Rebecca , Silverman, Edwin K. , Smith, Kevin S., Spillmann, Rebecca C. , Stoler, Joan M. , Sullivan, Jennifer A. , Tan, Queenie K.‐G., Tan, Wen-Haan, Toro, Camilo , Tran, Alyssa A., Urv, Tiina K. , Vogel, Tiphanie P. , Waggott, Daryl, Wahl, Colleen E., Walker, Melissa , Walley, Nicole M., Wan, Jijun , Ward, Patricia A., Westerfield, Monte, Wise, Anastasia L., Wolfe, Lynne A. , Yang, Yaping , Yoon, Amanda J., Yu, Guoyun, Zastrow, Diane B. , Zhao, Chunli , Zheng, Allison, Bunton-Stasyshyn, Rosie K , DeGennaro, Ellen M , Cascino, Gregory D , Giannini, Caterina , Burrage, Lindsay C , Rosenfield, Jill A , Bacino, Carlos , Lewis, Richard A , Segal, Rosalind A , Bazan, J Fernando , Smith, Kelly A , Golden, Jeffrey A , Cho, Ginam , Walsh, Christopher A , Alkuraya, Fowzan S , Akula, Shyam K , Shin, Taehwan , Giannini, Caterina , Network, Undiagnosed Diseases, Adams, David R. , Aday, Aaron W. , Allard, Patrick , Azamian, Mahshid S. , Beggs, Alan H. , Behnam, Babak , Bellen, Hugo J. , Berry, Gerard T. , Bonner, Devon E. , Brown, Donna M. , Burke, Elizabeth A. , Butte, Manish J. , Cogan, Joy D. , Cope, Heidi , D’Souza, Precilla , Douine, Emilie D. , Ferreira, Carlos R , Fieg, Elizabeth L. , Fisher, Paul Graham , Goldman, Alica M. , Gourdine, Jean-Philippe F. , Gropman, Andrea L , Haendel, Melissa , Holm, Ingrid A. , Huang, Yong , Jones, Angela , Kyle, Jennifer E , Lalani, Seema R , Levy, Shawn , Lewis, Richard A., Loo, Sandra K. , Macnamara, Ellen F. , Marom, Ronit , Martínez-Agosto, Julián A. , May, Thomas, Metz, Thomas , Might, Matthew , Mochida, Ganeshwaran H. , Mulvihill, John Joseph , Murphy, Jennifer L. , Muzny, Donna M. , Orange, Jordan S. , Phillips, John A., Posey, Jennifer E , Postlethwait, John H. , Reuter, Chloe M. , Rosenfeld, Jill A. , Scott, Daryl A , Sinsheimer, Janet S. , Stong, Nicholas , Sweetser, David A , Tifft, Cynthia , Vilain, Eric J. N. , Walley, Nicole M., Wangler, Michael F , Waters, Katrina M. , Webb‐Robertson, Bobbie‐Jo , Wheeler, Matthew T , Worthey, Elizabeth A. , Yamamoto, Shinya , Yang, John Jeongseok
Proceedings of the National Academy of Sciences | January 20, 2023 | Volume: 120 | Issue: 4 | Pages: No page available
Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B , which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret models, including leading to abnormal gyration in the ferret model. Tmem161b localizes non-exclusively to the primary cilium, and scanning electron microscopy revealed shortened, dysmorphic, and ballooned ventricular zone cilia in the Tmem161b null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify TMEM161B as a regulator of cerebral cortical gyration, as involved in primary ciliary structure, as a regulator of Shh signaling, and further implicate Shh signaling in human gyral development.
Genetic overlap between endometriosis and endometrial cancer: evidence from cross‐disease genetic correlation and GWAS meta‐analyses
Painter, Jodie N. , O’Mara, Tracy A. , Morris, Andrew P. , Cheng, Timothy, Gorman, Maggie, Martin, Lynn , Hodson, Shirley, Henders, Anjali K. , McEvoy, Mark , Holliday, Elizabeth , Scott, Rodney J. , Webb, Penelope M. , Fasching, Peter A. , Beckmann, Matthias W. , Ekici, Arif B. , Hein, Alexander , Rübner, Matthias, Dörk, Thilo , Hillemanns, Peter , Runnebaum, Ingo B. , Lambrechts, Diether , Annibali, Daniela , Depreeuw, Jeroen, Goode, Ellen L. , Cunningham, Julie M. , Dowdy, Sean C. , Trovik, Jone , Høivik, Erling A. , Werner, Henrica M.J., Krakstad, Camilla , Ashton, Katie A. , Otton, Geoffrey, Proietto, Tony, Tham, Emma , Mints, Miriam, Healey, Catherine S., Shah, Mitul , Bolla, Manjeet K. , Michailidou, Kyriaki , Wang, Qin , Hopper, John L. , Peto, Julian , Swerdlow, Anthony J. , Burwinkel, Barbara , Brenner, Hermann , Meindl, Alfons, Brauch, Hiltrud , Lindblom, Annika , Chang‐Claude, Jenny , Couch, Fergus J. , Kristensen, Vessela N. , Zondervan, Krina T. , Nyholt, Dale R. , MacGregor, Stuart , Tomlinson, Ian , Easton, Douglas F. , Thompson, Deborah J. , Lambrechts, Diether , Fasching, Peter A , Dörk, Thilo , Lambrechts, Diether , Goode, Ellen L , Webb, Penelope M , Hein, Alexander , Hillemanns, Peter , Swerdlow, Anthony J , O'Mara, Tracy A , Lambrechts, Diether , Brenner, Hermann , Ekici, Arif B , Michailidou, Kyriaki , MacGregor, Stuart , Jones, Angela , Martin, Nicholas G. , Gordon, Scott D. , Attia, John , Hall, Per N , Czene, Kamila , Dürst, Matthias , Amant, Frédéric , Vanderstichele, Adriaan , Winham, Stacey J. , Mints, Miriam , Ahmed, Shahana , Pharoah, Paul D.P. , Dunning, Alison M. , Dennis, Joe , Tyrer, Jonathan P. , Meindl, Alfons, Couch, Fergus J. , Giles, Graham G. , Cox, Angela , Montgomery, Grant W. , Spurdle, Amanda B. , Brauch, Hiltrud , Lindblom, Annika
Cancer Medicine | April 2, 2018 | Volume: 7 | Issue: 5 | Pages: 1978-1987
AbstractEpidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.