Sex differences in the genetic predictors of Alzheimer's pathology
Logan Dumitrescu, Lisa L Barnes, Madhav Thambisetty, Gary Beecham, Brian Kunkle, William S Bush, Katherine A Gifford, Lori B Chibnik et al.. Brain : a journal of neurology, 2019-09-01
Topic: Genetics and APOE
Autopsy measures of Alzheimer's disease neuropathology have been leveraged as endophenotypes in previous genome-wide association studies (GWAS). However, despite evidence of sex differences in Alzheimer's disease risk, sex-stratified models have not been incorporated into previous GWAS analyses. We looked for sex-specific genetic associations with Alzheimer's disease endophenotypes from six brain bank data repositories. The pooled dataset included 2701 males and 3275 females, the majority of whom were diagnosed with Alzheimer's disease at autopsy (70%). Sex-stratified GWAS were performed within each dataset and then meta-analysed. Loci that reached genome-wide significance (P < 5 × 10-8) in stratified models were further assessed for sex interactions. Additional analyses were performed in independent datasets leveraging cognitive, neuroimaging and CSF endophenotypes, along with age-at-onset data. Outside of the APOE region, one locus on chromosome 7 (rs34331204) showed a sex-specific association with neurofibrillary tangles among males (P = 2.5 × 10-8) but not females (P = 0.85, sex-interaction P = 2.9 × 10-4). In follow-up analyses, rs34331204 was also associated with hippocampal volume, executive function, and age-at-onset only among males. These results implicate a novel locus that confers male-specific protection from tau pathology and highlight the value of assessing genetic associations in a sex-specific manner.
Key findings
- In follow-up analyses, rs34331204 was also associated with hippocampal volume, executive function, and age-at-onset only among males.
- These results implicate a novel locus that confers male-specific protection from tau pathology and highlight the value of assessing genetic associations in a sex-specific manner.
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Study details
- Study designmeta-analysis
- Participants2,701
- Evidence strengthHigh
How this study scored 82/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported 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 46 of the 56 points we could judge it on, which is 82 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,701 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 | A review of other studies — randomisation is not credited here |
| 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 31497858) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 46 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 46 of the 56 points we could judge it on is 82 out of 100. |
| Total | 82 / 100 | — |
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APA 7th
Dumitrescu, L., Barnes, L. L., Thambisetty, M., Beecham, G., Kunkle, B., Bush, W. S., et al. (2019). Sex differences in the genetic predictors of Alzheimer's pathology. Brain : a journal of neurology. https://doi.org/10.1093/brain/awz206
Vancouver
Dumitrescu L, Barnes LL, Thambisetty M, Beecham G, Kunkle B, Bush WS, et al. Sex differences in the genetic predictors of Alzheimer's pathology. Brain : a journal of neurology. 2019. doi:10.1093/brain/awz206. PMID: 31497858.
BibTeX
@article{dumitrescu2019-31497858,
author = {Dumitrescu, Logan and Barnes, Lisa L and Thambisetty, Madhav and Beecham, Gary and Kunkle, Brian and Bush, William S and Gifford, Katherine A and Chibnik, Lori B and others},
title = {{Sex differences in the genetic predictors of Alzheimer's pathology}},
journal = {Brain : a journal of neurology},
year = {2019},
doi = {10.1093/brain/awz206},
pmid = {31497858},
url = {https://doi.org/10.1093/brain/awz206}
}