Abstract
Introduction: Multiple system atrophy (MSA) is a rare progressive neurodegenerative disorder. MSA was originally considered exclusively sporadic but reports of association with genes such as . SNCA, . COQ2 and . LRRK2 have demonstrated that there is a genetic contribution to the disease. . MAPT has been associated with several neurodegenerative diseases and we previously reported a protective association of the . MAPT H2 haplotype with MSA in 61 pathologically confirmed cases. Methods: In the present study, we assessed the full . MAPT haplotype diversity in MSA patients using six . MAPT tagging SNPs. We genotyped a total of 127 pathologically confirmed MSA cases, 86 patients with clinically diagnosed MSA and 1312 controls. Results: We identified four significant association signals in our pathologically confirmed cases, two from the protective haplotypes H2 (MSA:16.2%, Controls:22.7%, p = 0.024) and H1E (MSA:3.0%, Controls:9.0%, p = 0.014), and two from the rare risk haplotypes H1x (MSA:3.7%, Controls:1.3%, p = 0.030) and H1J (MSA:3.0%, Controls:0.9%, p = 0.021). We evaluated the association of MSA subtypes with the common protective H2 haplotype and found a significant difference with controls for MSA patients with some degree of MSA-C (MSA-C or MSA-mixed), for whom H2 occurred in only 8.6% of patients in our pathologically confirmed series (P < 0.0001). Conclusions: Our findings provide further evidence that . MAPT variation is associated with risk of MSA. Interestingly, our results suggest a greater effect size in the MSA-C compared to MSA-P for H2. Additional genetic studies in larger pathologically confirmed MSA series and meta-analytic studies will be needed to fully assess the role of . MAPT and other genes in MSA.
| Original language | English (US) |
|---|---|
| Journal | Parkinsonism and Related Disorders |
| DOIs | |
| State | Accepted/In press - Apr 14 2016 |
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Keywords
- Association study
- Genetics
- MAPT
- Multiple system atrophy
ASJC Scopus subject areas
- Geriatrics and Gerontology
- Clinical Neurology
- Neurology
Cite this
MAPT haplotype diversity in multiple system atrophy. / Labbé, Catherine; Heckman, Michael G.; Lorenzo-Betancor, Oswaldo; Murray, Melissa E; Ogaki, Kotaro; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Fujioka, Shinsuke; Koga, Shunsuke; Uitti, Ryan J.; Van Gerpen, Jay A; Petersen, Ronald Carl; Graff Radford, Neill R; Younkin, Steven G; Boeve, Bradley F; Cheshire, William P.; Low, Phillip Anson; Sandroni, Paola; Coon, Elizabeth; Singer, Wolfgang; Wszolek, Zbigniew K; Dickson, Dennis W; Ross, Owen A.
In: Parkinsonism and Related Disorders, 14.04.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MAPT haplotype diversity in multiple system atrophy
AU - Labbé, Catherine
AU - Heckman, Michael G.
AU - Lorenzo-Betancor, Oswaldo
AU - Murray, Melissa E
AU - Ogaki, Kotaro
AU - Soto-Ortolaza, Alexandra I.
AU - Walton, Ronald L.
AU - Fujioka, Shinsuke
AU - Koga, Shunsuke
AU - Uitti, Ryan J.
AU - Van Gerpen, Jay A
AU - Petersen, Ronald Carl
AU - Graff Radford, Neill R
AU - Younkin, Steven G
AU - Boeve, Bradley F
AU - Cheshire, William P.
AU - Low, Phillip Anson
AU - Sandroni, Paola
AU - Coon, Elizabeth
AU - Singer, Wolfgang
AU - Wszolek, Zbigniew K
AU - Dickson, Dennis W
AU - Ross, Owen A
PY - 2016/4/14
Y1 - 2016/4/14
N2 - Introduction: Multiple system atrophy (MSA) is a rare progressive neurodegenerative disorder. MSA was originally considered exclusively sporadic but reports of association with genes such as . SNCA, . COQ2 and . LRRK2 have demonstrated that there is a genetic contribution to the disease. . MAPT has been associated with several neurodegenerative diseases and we previously reported a protective association of the . MAPT H2 haplotype with MSA in 61 pathologically confirmed cases. Methods: In the present study, we assessed the full . MAPT haplotype diversity in MSA patients using six . MAPT tagging SNPs. We genotyped a total of 127 pathologically confirmed MSA cases, 86 patients with clinically diagnosed MSA and 1312 controls. Results: We identified four significant association signals in our pathologically confirmed cases, two from the protective haplotypes H2 (MSA:16.2%, Controls:22.7%, p = 0.024) and H1E (MSA:3.0%, Controls:9.0%, p = 0.014), and two from the rare risk haplotypes H1x (MSA:3.7%, Controls:1.3%, p = 0.030) and H1J (MSA:3.0%, Controls:0.9%, p = 0.021). We evaluated the association of MSA subtypes with the common protective H2 haplotype and found a significant difference with controls for MSA patients with some degree of MSA-C (MSA-C or MSA-mixed), for whom H2 occurred in only 8.6% of patients in our pathologically confirmed series (P < 0.0001). Conclusions: Our findings provide further evidence that . MAPT variation is associated with risk of MSA. Interestingly, our results suggest a greater effect size in the MSA-C compared to MSA-P for H2. Additional genetic studies in larger pathologically confirmed MSA series and meta-analytic studies will be needed to fully assess the role of . MAPT and other genes in MSA.
AB - Introduction: Multiple system atrophy (MSA) is a rare progressive neurodegenerative disorder. MSA was originally considered exclusively sporadic but reports of association with genes such as . SNCA, . COQ2 and . LRRK2 have demonstrated that there is a genetic contribution to the disease. . MAPT has been associated with several neurodegenerative diseases and we previously reported a protective association of the . MAPT H2 haplotype with MSA in 61 pathologically confirmed cases. Methods: In the present study, we assessed the full . MAPT haplotype diversity in MSA patients using six . MAPT tagging SNPs. We genotyped a total of 127 pathologically confirmed MSA cases, 86 patients with clinically diagnosed MSA and 1312 controls. Results: We identified four significant association signals in our pathologically confirmed cases, two from the protective haplotypes H2 (MSA:16.2%, Controls:22.7%, p = 0.024) and H1E (MSA:3.0%, Controls:9.0%, p = 0.014), and two from the rare risk haplotypes H1x (MSA:3.7%, Controls:1.3%, p = 0.030) and H1J (MSA:3.0%, Controls:0.9%, p = 0.021). We evaluated the association of MSA subtypes with the common protective H2 haplotype and found a significant difference with controls for MSA patients with some degree of MSA-C (MSA-C or MSA-mixed), for whom H2 occurred in only 8.6% of patients in our pathologically confirmed series (P < 0.0001). Conclusions: Our findings provide further evidence that . MAPT variation is associated with risk of MSA. Interestingly, our results suggest a greater effect size in the MSA-C compared to MSA-P for H2. Additional genetic studies in larger pathologically confirmed MSA series and meta-analytic studies will be needed to fully assess the role of . MAPT and other genes in MSA.
KW - Association study
KW - Genetics
KW - MAPT
KW - Multiple system atrophy
UR - http://www.scopus.com/inward/record.url?scp=84979695272&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979695272&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2016.06.010
DO - 10.1016/j.parkreldis.2016.06.010
M3 - Article
C2 - 27374978
AN - SCOPUS:84979695272
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
ER -