Chelban, Viorica
Mayo Clinic
UCL Queen Square Institute of Neurology
Citations 2
Chromosome X-wide association study in multiple system atrophy identifies sex-differential risk loci
Ray, Anindita , Chia, Ruth , Rasheed, Memoona, Ece, Bayram, Jinhui, Ding, Walton, Ronald L., Diez-Fairen, Monica, Álvarez, Ignacio Morales, Fanciulli, Alessandra , Seppi, Mag Klaus, Duerr, Susanne, Leys, Fabian , Krismer, Florian , Sidoroff, Victoria , Pirker, Walter , Rascol, Olivier, Foubert-Samier, Alexandra, Meissner, Wassilios G, Tison, François , Barone, Paolo, Russillo, Maria Claudia, Marín-Lahoz, Juan, Kulisevsky, J, Torres, Soraya, Mir, Pablo, Periñán, María Teresa, Proukakis, C., Goh, Yee Yen, Parkkinen, Laura, Hu, Michele T, Saxon, Jennifer A. , Rollinson, Sara , Garland, Emily M. , Litvan, Irene, Alcalay, Roy N, Kwei, Kimberly , Lubbe, Steven, Mao, Qinwen, Flanagan, Margaret E, Castellani, Rudolph J, Ndayisaba, Alain , Calvo, Andrea, Canosa, Antonio, Bohannan, Ryan C., Norcliffe-Kaufmann, Lucy, Palma, Jose-Alberto, Dawson, Ted M, Albert, Marilyn S, Pletniková, Olga , Troncoso, Juan C, Lage, Carmen , Sánchez-Juan, Pascual, Serrano, Geidy E, Beach, Thomas G, Morris, Huw R, Clarimon, Jordi, Jaunmuktane, Zane, Révész, Tamás, Warner, Tom, Hardy, John A, Ryten, Mina, Ferrucci, Luigi, Topol, Eric, Torkamani, Ali, DeCasien, Alex R, Chiò, Adriano, Low, Philip, Wszolek, Zbigniew K, Dickson, Dennis W., Traynor, Bryan J, Gibbs, J Raphael, Dalgard, Clifton L, Ross, Owen A, Houlden, Henry, Scholz, Sonja W., Hardy, John , Dickson, Dennis W. , Ross, Owen A. , Houlden, Henry , Scholz, Sonja W. , Chia, Ruth , Proukakis, Christos , Dickson, Dennis W , Dalgard, Clifton L , Ross, Owen A , Houlden, Henry , Scholz, Sonja W , Hardy, John , Reynolds, Regina H. , Díez-Fairén, Mónica , Fanciulli, Alessandra , Stefanova, Nadia , Seppi, Klaus , Krismer, Florian, Zimprich, Alexander , Rascol, Olivier , Foubert‐Samier, Alexandra , Meissner, Wassilios G. , Tison, François , Traon, Anne Pavy‐Le , Pellecchia, Maria Teresa , Marín‐Lahoz, Juan , Kulisevsky, Jaime , Mir, Pablo , Chelban, Viorica , Wu, Lesley , Kobylecki, Christopher , Biaggioni, Italo , Litvan, Irene , Rubio, Ileana, Lubbe, Steven , Flanagan, Margaret E , Castellani, Rudolph J. , Khurana, Vikram , Mora, Gabriele , Floris, Gianluca , Moore, Anni K. , Norcliffe‐Kaufmann, Lucy , Palma, Jose-Alberto , Kaufmann, Horacio , Dawson, Ted M , Rosenthal, Liana S. , Pantelyat, Alexander , Troncoso, Juan C. , Infante, Jon , Serrano, Geidy E. , Beach, Thomas G. , Pástor, Pau , Albani, Diego , Clarimón, Jordi , Jaunmuktane, Zane , Frontzek, Karl , Warner, Thomas T. , Ferrucci, Luigi , Topol, Eric J. , Torkamani, Ali , DeCasien, Alex R. , Chiò, Adriano , Singer, Wolfgang , Cheshire, William P. , Wszołek, Zbigniew K. , Traynor, Bryan J. , Gibbs, J. Raphael
Brain | February 12, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract The human X chromosome accounts for ∼5% of the genome. Despite its size, the role of X-chromosomal variants in human diseases is not well understood, mainly due to its distinct inheritance pattern and the frequent omission of sex chromosomes from genome-wide association studies. This study used whole-genome sequencing data from 888 multiple system atrophy (MSA) cases and 7128 controls to perform an X-chromosome-wide common variant association study. Our analyses revealed two sex-differential risk loci: one located at Xq28, associated with increased risk for MSA in females [index variant: rs4898389, odds ratio (OR) = 1.69, 95% confidence interval (CI) = 1.40–2.03, P-value = 2.43 × 10⁻⁸], and another at Xp22.2 within the TBL1X gene, identified in males (index variant: rs6638956, OR = 1.48, 95%CI = 1.26–1.73, P-value = 9.92 × 10⁻⁷). In the Xq28 locus, colocalization analyses pointed to FAM3A and PLXNA3 as genes of interest. These findings emphasize the vital role of sex-differential genetic factors in the pathogenesis of MSA.
Genome-wide association analysis identifies PLA2G4C as a susceptibility locus for Multiple System Atrophy
Tsuji, Shoji , Nakahara, Yasuo , Mitsui, Jun , Date, Hidetoshi, Porto, Kristine Joyce L. , Hyashi, Y., Kusakabe, Yoshio , Matsukawa, Takashi , Ishiura, Hiroyuki , Yasuda, Tsutomu , Goto, Jun , Ichikawa, Yaeko, Momose, Yoshio, Takahashi, Yuji , Ohta, Rikifumi , Yoshimura, Jun , Gustavsson, Emil K. , Christy, Darren, Maczis, Melisa, Gu, Weihong, Scholz, Sonja W. , Houlden, Henry , Sasaki, Hidenao , Kikuchi, Akio , Hara, Kenju , Kakita, Akiyoshi , Yamada, Mitsunori , Nishizawa, Masatoyo , Ito, Mizuki , Sobue, Gen , Ishikawa, Kinya , Mizusawa, Hidehiro, Kanai, Kazuaki , Arai, Kimihito , Koyano, Shigeru , Kuroiwa, Yoshiyuki , Hasegawa, Kazuko, Yuasa, Tatsuhiko, Yasui, Kenichi, Ito, Hijiri, Izumi, Yuishin , Kaji, Ryuji , Kato, Takeo , Kusunoki, Susumu , Osaki, Yasushi , Horiuchi, Masahiro , Yamamoto, Ken , Shimada, Mihoko , Miyagawa, Taku , Nishida, Nao , Tokunaga, Katsushi , Filla, Alessandro , Klockgether, Thomas , Wuellner, Ullrich, Kukull, Walter A. , Masliah, Eliezer , Low, Phillip A. , Sandroni, Paola , Ozelius, Laurie J. , Trojanowski, John Q. , Scholz, Sonja W , Houlden, Henry , Yamashita, Atsushi , Yasuda, Tsutomu, Iwata, Atsushi , Toda, Tatsushi , Morishita, Shinichi , Kim, Han‐Joon , Park, Sung Sup , Zhang, Jin , Chelban, Viorica , Mok, Kin Ying , Yabe, Ichiro , Matsushima, Masaaki , Takashima, Hiroshi , Aoki, Masashi , Takahashi, Hitoshi , Onodera, Osamu , Watanabe, Hirohisa , Kuwabara, Satoshi , Nakashima, Kenji , Horiuchi, Masahiro, Kawai, Yosuke , Dürr, Alexandra , Brice, Alexis , Tanner, Caroline M. , Lee, Virginia M.‐Y. , Foroud, Tatiana , Farrer, Matthew J.
No container title available | February 6, 2024 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European, and North American samples. In the GWAS stage, rs2303744 on chromosome 19 showed a suggestive association (P = 6.5 × 10− 7) that was replicated in additional Japanese samples (P = 2.9 × 10− 6, odds ratio (OR) = 1.58; 95% confidence interval (CI), 1.30–1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data (P = 5.0 × 10− 15, OR = 1.49; 95% CI 1.35–1.65). The association of rs2303744 with MSA remained significant in combined European/North American samples (P = 0.017, OR = 1.12; 95% CI 1.02–1.23) despite allele frequencies being quite different between these populations. rs2303744 leads to an amino acid substitution in PLA2G4C that encodes the cPLA2γ lysophospholipase/transacylase. The cPLA2γ-Ile143 isoform encoded by the MSA risk allele has significantly decreased transacylase activity compared with the alternate cPLA2γ-Val143 isoform, and may perturb membrane phospholipids and promote oligodendroglial pathology.