| Autor: |
Nakahara Y, Mitsui J, Date H, Porto KJ, Hayashi Y, Yamashita A, Kusakabe Y, Matsukawa T, Ishiura H, Yasuda T, Iwata A, Goto J, Ichikawa Y, Momose Y, Takahashi Y, Toda T, Ohta R, Yoshimura J, Morishita S, Gustavsson EK, Christy D, Maczis M, Farrer MJ, Kim HJ, Park SS, Jeon B, Zhang J, Gu W, Scholz SW, Singleton AB, Houlden H, Yabe I, Sasaki H, Matsushima M, Takashima H, Kikuchi A, Aoki M, Hara K, Kakita A, Yamada M, Takahashi H, Onodera O, Nishizawa M, Watanabe H, Ito M, Sobue G, Ishikawa K, Mizusawa H, Kanai K, Kuwabara S, Arai K, Koyano S, Kuroiwa Y, Hasegawa K, Yuasa T, Yasui K, Nakashima K, Ito H, Izumi Y, Kaji R, Kato T, Kusunoki S, Osaki Y, Horiuchi M, Yamamoto K, Shimada M, Miyagawa T, Kawai Y, Nishida N, Tokunaga K, Dürr A, Brice A, Filla A, Klockgether T, Wüllner U, Tanner CM, Kukull WA, Lee VM, Masliah E, Low PA, Sandroni P, Ozelius L, Foroud T, Tsuji S |
| Jazyk: |
angličtina |
| Zdroj: |
MedRxiv : the preprint server for health sciences [medRxiv] 2023 May 02. Date of Electronic Publication: 2023 May 02. |
| DOI: |
10.1101/2023.05.02.23289328 |
| Abstrakt: |
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 . OR = 1.58; 95% confidence interval, 1.30 to 1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data ( P = 5.0 × 10 -15 . Odds ratio= 1.49; 95% CI 1.35 to 1.72). The association of rs2303744 with MSA remained significant in combined European/North American samples ( P =0.023. Odds ratio=1.14; 95% CI 1.02 to 1.28) 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 that may perturb membrane phospholipids and α-synuclein biology. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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