MAPT haplotype-stratified GWAS reveals differential association for AD risk variants
Samantha L Strickland, Joseph S Reddy, Mariet Allen, Aurelie N'songo, Jeremy D Burgess, Morgane M Corda, Travis Ballard, Xue Wang et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2020-05-13
Topic: Genetics and APOE
We identified 11 loci-5 in H2-non-carriers and 6 in H2-carriers-although none of the MAPT haplotype-specific associations achieved genome-wide significance. The most significant H2 non-carrier-specific association was with a NECTIN2 intronic (P = 1.33E-07) variant, and that for H2 carriers was near NKX6-1 (P = 1.99E-06). The GABRG2 locus had the strongest epistasis with MAPT H1/H2 variant rs8070723 (P = 3.91E-06). Eight of the 12 genes at these loci had transcriptome-wide significant differential expression in AD versus control temporal cortex (q < 0.05). Six genes were members of the brain transcriptional co-expression network implicated in "synaptic transmission" (P = 9.85E-59), which is also enriched for neuronal genes (P = 1.0E-164), including MAPT. This stratified GWAS identified loci that may confer AD risk in a MAPT haplotype-specific manner. This approach may preferentially enrich for neuronal genes implicated in synaptic transmission.
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APA 7th
Strickland, S. L., Reddy, J. S., Allen, M., N'songo, A., Burgess, J. D., Corda, M. M., et al. (2020). MAPT haplotype-stratified GWAS reveals differential association for AD risk variants. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.12099
Vancouver
Strickland SL, Reddy JS, Allen M, N'songo A, Burgess JD, Corda MM, et al. MAPT haplotype-stratified GWAS reveals differential association for AD risk variants. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2020. doi:10.1002/alz.12099. PMID: 32400971.
BibTeX
@article{strickland2020-32400971,
author = {Strickland, Samantha L and Reddy, Joseph S and Allen, Mariet and N'songo, Aurelie and Burgess, Jeremy D and Corda, Morgane M and Ballard, Travis and Wang, Xue and others},
title = {{MAPT haplotype-stratified GWAS reveals differential association for AD risk variants}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2020},
doi = {10.1002/alz.12099},
pmid = {32400971},
url = {https://doi.org/10.1002/alz.12099}
}
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Key findings
- We identified 11 loci-5 in H2-non-carriers and 6 in H2-carriers-although none of the MAPT haplotype-specific associations achieved genome-wide significance.
- The most significant H2 non-carrier-specific association was with a NECTIN2 intronic (P = 1.33E-07) variant, and that for H2 carriers was near NKX6-1 (P = 1.99E-06).
- The GABRG2 locus had the strongest epistasis with MAPT H1/H2 variant rs8070723 (P = 3.91E-06).
- Eight of the 12 genes at these loci had transcriptome-wide significant differential expression in AD versus control temporal cortex (q < 0.05).
- Six genes were members of the brain transcriptional co-expression network implicated in "synaptic transmission" (P = 9.85E-59), which is also enriched for neuronal genes (P = 1.0E-164), including MAPT.
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Study details
- Participants18,841
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 31 of the 56 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 4 / 4 | 18,841 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32400971) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 31 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 31 of the 56 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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