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Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease
Lambert JC, Grenier-Boley B, Harold D, Zelenika D, Chouraki V, Kamatani Y, Sleegers K, Ikram MA et al.. Molecular psychiatry, 2012-03-20
Topic: Genetics and APOE
Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 × 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and Aβ plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
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APA 7th
Lambert, J. C., Grenier-Boley, B., Harold, D., Zelenika, D., Chouraki, V., Kamatani, Y., et al. (2013). Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease. Molecular psychiatry. https://doi.org/10.1038/mp.2012.14
Vancouver
Lambert JC, Grenier-Boley B, Harold D, Zelenika D, Chouraki V, Kamatani Y, et al. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease. Molecular psychiatry. 2013. doi:10.1038/mp.2012.14. PMID: 22430674.
BibTeX
@article{lambert2013-22430674,
author = {Lambert, J. C. and Grenier-Boley, B. and Harold, D. and Zelenika, D. and Chouraki, V. and Kamatani, Y. and Sleegers, K. and Ikram, M. A. and others},
title = {{Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease}},
journal = {Molecular psychiatry},
year = {2013},
doi = {10.1038/mp.2012.14},
pmid = {22430674},
url = {https://doi.org/10.1038/mp.2012.14}
}
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Key findings
- We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10(-7)).
- In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
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Study details
- Study designcase-control study
- Participants2,025
- Effect sizeOR: 1.68
- Evidence strengthModerate
How this study scored 72/100
Published in a leading specialty journal, and it is a case-control study. Scored zero for 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 and institution's track record, so those were left out: it earned 44 of the 61 points we could judge it on, which is 72 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,025 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22430674) |
| Free to read | 2 / 2 | Free to read |
| Points | 44 / 61 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 44 of the 61 points we could judge it on is 72 out of 100. |
| Total | 72 / 100 | — |
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