Topic: Risk, prevention and care in population studies
Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits' genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics. Through theoretical and numerical analyses, we demonstrate that our method provides accurate covariance estimates, thereby enabling researchers to dissect both the shared and distinct genetic architecture across traits to better understand their etiologies. Among 50 complex traits with publicly accessible GWAS summary statistics (N total ≈ 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance. In particular, we found strong genetic covariance between late-onset Alzheimer disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome. Joint analysis of LOAD, ALS, and other traits highlights LOAD's correlation with cognitive traits and hints at an autoimmune component for ALS.
Key findings
- Among 50 complex traits with publicly accessible GWAS summary statistics (N total ≈ 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance.
- In particular, we found strong genetic covariance between late-onset Alzheimer disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome.
Why it matters
This statistical method found shared genetic covariance between late-onset Alzheimer disease and amyotrophic lateral sclerosis, along with links between Alzheimer's and cognitive traits. It is a genetic analysis and does not provide a treatment, cure or prevention.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 49/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (American journal of human genetics) |
| Journal's citation record | 3 / 4 | The American Journal of Human Genetics: journal h-index 385 (OpenAlex, 2026-10-29) |
| 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 | 2017 — within 10 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 | 5 / 7 | Cited 222 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.2 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 3 / 6 | Cited 4.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 3 / 4 | Cited 97 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Hongyu Zhao: h-index 113 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29220677) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Lu, Q., Li, B., Ou, D., Erlendsdottir, M., Powles, R. L., Jiang, T., et al. (2017). A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics. American journal of human genetics. https://doi.org/10.1016/j.ajhg.2017.11.001
Vancouver
Lu Q, Li B, Ou D, Erlendsdottir M, Powles RL, Jiang T, et al. A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics. American journal of human genetics. 2017. doi:10.1016/j.ajhg.2017.11.001. PMID: 29220677.
BibTeX
@article{lu2017-29220677,
author = {Lu, Q. and Li, B. and Ou, D. and Erlendsdottir, M. and Powles, R. L. and Jiang, T. and Hu, Y. and Chang, D. and others},
title = {{A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics}},
journal = {American journal of human genetics},
year = {2017},
doi = {10.1016/j.ajhg.2017.11.001},
pmid = {29220677},
url = {https://doi.org/10.1016/j.ajhg.2017.11.001}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
2 studies in the alzhub library list this one in their references.
Related studies in Genetics
Also in Genetics
173 studies in the library are filed under Genetics with no topic tag they share with another; these are this study's neighbours in a fixed tour of them. The Genetics hub.