Topic: Genetics and APOE
Both social and genetic factors contribute to cognitive impairment and decline, yet genetic factors identified through genome-wide association studies (GWAS) explain only a small portion of trait variability. This "missing heritability" may be due to rare, potentially functional, genetic variants not assessed by GWAS, as well as gene-by-social factor interactions not explicitly modeled. Gene-by-social factor interactions may also operate differently across race/ethnic groups. We selected 39 genes that had significant, replicated associations with cognition, dementia, and related traits in published GWAS. Using gene-based analysis (SKAT/iSKAT), we tested whether common and/or rare variants were associated with episodic memory performance and decline either alone or through interaction with education in >10,000 European ancestry (EA) and >2200 African ancestry (AA) respondents from the Health and Retirement Study (HRS). Nine genes in EA and five genes in AA were associated with memory performance or decline (p < 0.05), and these effects did not attenuate after adjusting for education. Interaction between education and CLPTM1 on memory performance was significant in AA (p = 0.003; FDR-adjusted p = 0.038) and nominally significant in EA (p = 0.026). In both ethnicities, low memory performance was associated with CLPTM1 genotype (rs10416261) only for those with less than high school education, and effects persisted after adjusting for APOE ε4. For over 70% of gene-by-education interactions across the genome that were at least nominally significant in either ethnic group (p < 0.05), genetic effects were only observed for those with less than high school education. These results suggest that genetic effects on memory identified in this study are not mediated by education, but there may be important gene-by-education interactions across the genome, including in the broader APOE genomic region, which operate independently of APOE ε4. This work illustrates the importance of developing theoretical frameworks and methodological approaches for integrating social and genomic data to study cognition across ethnic groups.
Key findings
- We selected 39 genes that had significant, replicated associations with cognition, dementia, and related traits in published GWAS.
- Using gene-based analysis (SKAT/iSKAT), we tested whether common and/or rare variants were associated with episodic memory performance and decline either alone or through interaction with education in >10,000 European ancestry (EA) and >2200 African ancestry (AA) respondents from the Health and Retirement Study (HRS).
- Nine genes in EA and five genes in AA were associated with memory performance or decline (p < 0.05), and these effects did not attenuate after adjusting for education.
- Interaction between education and CLPTM1 on memory performance was significant in AA (p = 0.003; FDR-adjusted p = 0.038) and nominally significant in EA (p = 0.026).
- In both ethnicities, low memory performance was associated with CLPTM1 genotype (rs10416261) only for those with less than high school education, and effects persisted after adjusting for APOE ε4.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people 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 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Social science & medicine (1982)) |
| 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 30449520) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Smith, J. A., Kho, M., Zhao, W., Yu, M., Mitchell, C., & Faul, J. D. (2021). Genetic effects and gene-by-education interactions on episodic memory performance and decline in an aging population. Social science & medicine (1982). https://doi.org/10.1016/j.socscimed.2018.11.019
Vancouver
Smith JA, Kho M, Zhao W, Yu M, Mitchell C, Faul JD. Genetic effects and gene-by-education interactions on episodic memory performance and decline in an aging population. Social science & medicine (1982). 2021. doi:10.1016/j.socscimed.2018.11.019. PMID: 30449520.
BibTeX
@article{smith2021-30449520,
author = {Smith, Jennifer A and Kho, Minjung and Zhao, Wei and Yu, Miao and Mitchell, Colter and Faul, Jessica D},
title = {{Genetic effects and gene-by-education interactions on episodic memory performance and decline in an aging population}},
journal = {Social science \& medicine (1982)},
year = {2021},
doi = {10.1016/j.socscimed.2018.11.019},
pmid = {30449520},
url = {https://doi.org/10.1016/j.socscimed.2018.11.019}
}
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