Topic: Genetics and APOE
Large case/control genome-wide association studies (GWAS) often include groups of related individuals with known relationships. When testing for associations at a given locus, current methods incorporate only the familial relationships between individuals. Here, we introduce the chromosome-based Quasi Likelihood Score (cQLS) statistic that incorporates local Identity-By-Descent (IBD) to increase the power to detect associations. In studies robust to population stratification, such as those with case/control sibling pairs, simulations show that the study power can be increased by over 50%. In our example, a GWAS examining late-onset Alzheimers disease, the p-values among the most strongly associated SNPs in the APOE gene tend to decrease, with the smallest p-value decreasing from 1.23 × 10-8 to 7.70 × 10-9. Furthermore, as a part of our simulations, we reevaluate our expectations about the use of families in GWAS. We show that, although adding only half as many unique chromosomes, genotyping affected siblings is more efficient than genotyping randomly ascertained cases. We also show that genotyping cases with a family history of disease will be less beneficial when searching for SNPs with smaller effect sizes.
Key findings
- In studies robust to population stratification, such as those with case/control sibling pairs, simulations show that the study power can be increased by over 50%.
- In our example, a GWAS examining late-onset Alzheimers disease, the p-values among the most strongly associated SNPs in the APOE gene tend to decrease, with the smallest p-value decreasing from 1.23 × 10-8 to 7.70 × 10-9.
- Furthermore, as a part of our simulations, we reevaluate our expectations about the use of families in GWAS.
- We show that, although adding only half as many unique chromosomes, genotyping affected siblings is more efficient than genotyping randomly ascertained cases.
- We also show that genotyping cases with a family history of disease will be less beneficial when searching for SNPs with smaller effect sizes.
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Study details
- Evidence strengthLow
How this study scored 38/100
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 21 of the 56 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The annals of applied statistics) |
| 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 | 1 / 5 | 2014 — within 20 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 25544865) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 21 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 21 of the 56 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Sampson, J. N., Wheeler, B., Li, P., & Shi, J. (2014). LEVERAGING LOCAL IDENTITY-BY-DESCENT INCREASES THE POWER OF CASE/CONTROL GWAS WITH RELATED INDIVIDUALS. The annals of applied statistics. https://doi.org/10.1214/14-aoas715
Vancouver
Sampson JN, Wheeler B, Li P, Shi J. LEVERAGING LOCAL IDENTITY-BY-DESCENT INCREASES THE POWER OF CASE/CONTROL GWAS WITH RELATED INDIVIDUALS. The annals of applied statistics. 2014. doi:10.1214/14-aoas715. PMID: 25544865.
BibTeX
@article{sampson2014-25544865,
author = {Sampson, Joshua N and Wheeler, Bill and Li, Peng and Shi, Jianxin},
title = {{LEVERAGING LOCAL IDENTITY-BY-DESCENT INCREASES THE POWER OF CASE/CONTROL GWAS WITH RELATED INDIVIDUALS}},
journal = {The annals of applied statistics},
year = {2014},
doi = {10.1214/14-aoas715},
pmid = {25544865},
url = {https://doi.org/10.1214/14-aoas715}
}
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