| Title |
Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerative diseases
|
|---|---|
| Published in |
Molecular Neurodegeneration, August 2018
|
| DOI | 10.1186/s13024-018-0270-8 |
| Pubmed ID | |
| Authors |
Jason A. Chen, Zhongbo Chen, Hyejung Won, Alden Y. Huang, Jennifer K. Lowe, Kevin Wojta, Jennifer S. Yokoyama, Gilbert Bensimon, P. Nigel Leigh, Christine Payan, Aleksey Shatunov, Ashley R. Jones, Cathryn M. Lewis, Panagiotis Deloukas, Philippe Amouyel, Christophe Tzourio, Jean-Francois Dartigues, Albert Ludolph, Adam L. Boxer, Jeff M. Bronstein, Ammar Al-Chalabi, Daniel H. Geschwind, Giovanni Coppola |
| Abstract |
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease for which the genetic contribution is incompletely understood. We conducted a joint analysis of 5,523,934 imputed SNPs in two newly-genotyped progressive supranuclear palsy cohorts, primarily derived from two clinical trials (Allon davunetide and NNIPPS riluzole trials in PSP) and a previously published genome-wide association study (GWAS), in total comprising 1646 cases and 10,662 controls of European ancestry. We identified 5 associated loci at a genome-wide significance threshold P < 5 × 10- 8, including replication of 3 loci from previous studies and 2 novel loci at 6p21.1 and 12p12.1 (near RUNX2 and SLCO1A2, respectively). At the 17q21.31 locus, stepwise regression analysis confirmed the presence of multiple independent loci (localized near MAPT and KANSL1). An additional 4 loci were highly suggestive of association (P < 1 × 10- 6). We analyzed the genetic correlation with multiple neurodegenerative diseases, and found that PSP had shared polygenic heritability with Parkinson's disease and amyotrophic lateral sclerosis. In total, we identified 6 additional significant or suggestive SNP associations with PSP, and discovered genetic overlap with other neurodegenerative diseases. These findings clarify the pathogenesis and genetic architecture of PSP. |
X Demographics
The data shown below were collected from the profiles of 26 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 12 | 46% |
| United Kingdom | 5 | 19% |
| Pakistan | 1 | 4% |
| Unknown | 8 | 31% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 14 | 54% |
| Scientists | 11 | 42% |
| Science communicators (journalists, bloggers, editors) | 1 | 4% |
Mendeley readers
The data shown below were compiled from readership statistics for 77 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 77 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 13% |
| Student > Bachelor | 10 | 13% |
| Student > Doctoral Student | 7 | 9% |
| Other | 6 | 8% |
| Student > Ph. D. Student | 5 | 6% |
| Other | 16 | 21% |
| Unknown | 23 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 13 | 17% |
| Neuroscience | 12 | 16% |
| Medicine and Dentistry | 8 | 10% |
| Agricultural and Biological Sciences | 6 | 8% |
| Immunology and Microbiology | 2 | 3% |
| Other | 8 | 10% |
| Unknown | 28 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 25. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 November 2023.
All research outputs
#1,452,343
of 24,625,114 outputs
Outputs from Molecular Neurodegeneration
#112
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Outputs of similar age
#30,474
of 335,592 outputs
Outputs of similar age from Molecular Neurodegeneration
#5
of 17 outputs
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