Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE
Klimentidis YC, Raichlen DA, Bea J, Garcia DO, Wineinger NE, Mandarino LJ, Alexander GE, Chen Z et al.. International journal of obesity (2005), 2018-06-13
Topic: Genetics and APOE
Background/objectives Physical activity (PA) protects against a wide range of diseases. Habitual PA appears to be heritable, motivating the search for specific genetic variants that may inform efforts to promote PA and target the best type of PA for each individual. Subjects/methods We used data from the UK Biobank to perform the largest genome-wide association study of PA to date, using three measures based on self-report (n max = 377,234) and two measures based on wrist-worn accelerometry data (n max = 91,084). We examined genetic correlations of PA with other traits and diseases, as well as tissue-specific gene expression patterns. With data from the Atherosclerosis Risk in Communities (ARIC; n = 8,556) study, we performed a meta-analysis of our top hits for moderate-to-vigorous PA (MVPA). Results We identified ten loci across all PA measures that were significant in both a basic and a fully adjusted model (p < 5 × 10 -9 ). Upon meta-analysis of the nine top hits for MVPA with results from ARIC, eight were genome-wide significant. Interestingly, among these, the rs429358 variant in the APOE gene was the most strongly associated with MVPA, whereby the allele associated with higher Alzheimer's risk was associated with greater MVPA. However, we were not able to rule out possible selection bias underlying this result. Variants in CADM2, a gene previously implicated in obesity, risk-taking behavior and other traits, were found to be associated with habitual PA. We also identified three loci consistently associated (p < 5 × 10 -5 ) with PA across both self-report and accelerometry, including CADM2. We found genetic correlations of PA with educational attainment, chronotype, psychiatric traits, and obesity-related traits. Tissue enrichment analyses implicate the brain and pituitary gland as locations where PA-associated loci may exert their actions. Conclusions These results provide new insight into the genetic basis of habitual PA, and the genetic links connecting PA with other traits and diseases.
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APA 7th
Klimentidis, Y. C., Raichlen, D. A., Bea, J., Garcia, D. O., Wineinger, N. E., Mandarino, L. J., et al. (2018). Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. International journal of obesity (2005). https://doi.org/10.1038/s41366-018-0120-3
Vancouver
Klimentidis YC, Raichlen DA, Bea J, Garcia DO, Wineinger NE, Mandarino LJ, et al. Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. International journal of obesity (2005). 2018. doi:10.1038/s41366-018-0120-3. PMID: 29899525.
BibTeX
@article{klimentidis2018-29899525,
author = {Klimentidis, Y. C. and Raichlen, D. A. and Bea, J. and Garcia, D. O. and Wineinger, N. E. and Mandarino, L. J. and Alexander, G. E. and Chen, Z. and others},
title = {{Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE}},
journal = {International journal of obesity (2005)},
year = {2018},
doi = {10.1038/s41366-018-0120-3},
pmid = {29899525},
url = {https://doi.org/10.1038/s41366-018-0120-3}
}
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Key findings
- Results We identified ten loci across all PA measures that were significant in both a basic and a fully adjusted model (p < 5 × 10 -9 ).
- Upon meta-analysis of the nine top hits for MVPA with results from ARIC, eight were genome-wide significant.
- Interestingly, among these, the rs429358 variant in the APOE gene was the most strongly associated with MVPA, whereby the allele associated with higher Alzheimer's risk was associated with greater MVPA.
- However, we were not able to rule out possible selection bias underlying this result.
- Variants in CADM2, a gene previously implicated in obesity, risk-taking behavior and other traits, were found to be associated with habitual PA.
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Study details
- Study designmeta-analysis
- Participants8,556
- Evidence strengthHigh
How this study scored 79/100
Published in a peer-reviewed 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 and multicenter collaboration, so those were left out: it earned 46 of the 58 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International journal of obesity (2005)) |
| 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 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 8,556 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) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29899525) |
| Free to read | 2 / 2 | Free to read |
| Points | 46 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 46 of the 58 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
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