Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back pain
Abstract This multi-ancestry meta-analysis of genome-wide association studies (GWAS) investigated the genetic factors underlying chronic back pain (CBP) in a sample from the Million Veteran Program comprised of 553,601 Veterans of African (19.2%), European (72.6%), and Hispanic (8.2%) ancestry. The...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55326-3 |
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| author | Ian B. Stanaway Pradeep Suri Niloofar Afari Daniel Dochtermann Armand Gerstenberger Saiju Pyarajan Eric J. Roseen Million Veteran Program Marianna Gasperi |
| author_facet | Ian B. Stanaway Pradeep Suri Niloofar Afari Daniel Dochtermann Armand Gerstenberger Saiju Pyarajan Eric J. Roseen Million Veteran Program Marianna Gasperi |
| author_sort | Ian B. Stanaway |
| collection | DOAJ |
| description | Abstract This multi-ancestry meta-analysis of genome-wide association studies (GWAS) investigated the genetic factors underlying chronic back pain (CBP) in a sample from the Million Veteran Program comprised of 553,601 Veterans of African (19.2%), European (72.6%), and Hispanic (8.2%) ancestry. The results revealed novel (N = 67) and known (N = 20) genome-wide significant loci associated with CBP, with 43 independent variants replicating in a non-overlapping contemporary meta-GWAS of the spinal pain dorsalgia phenotype. The most significant novel variant was rs12533005 (chr7:114416000, p = 1.61 × 10−20, OR = 0.96 (95% CI: 0.95–0.97), EA = C, EAF = 0.39), in an intron of the FOXP2 gene. In silico functional characterization revealed enrichment in brain and pituitary tissues. Mendelian randomization analysis of 62 variants for CBP-MVP revealed 48 with causal links to dorsalgia. Notably, four genes (INPP5B, DRD2, HTT, SLC30A6) associated with these variants are targets of existing drugs. Our findings more than double the number of previously reported genetic predictors across all spinal pain phenotypes. |
| format | Article |
| id | doaj-art-fe4b5bf331dd4f4c9891285ec1d912b7 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-fe4b5bf331dd4f4c9891285ec1d912b72025-08-20T02:59:57ZengNature PortfolioNature Communications2041-17232025-02-0116111210.1038/s41467-024-55326-3Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back painIan B. Stanaway0Pradeep Suri1Niloofar Afari2Daniel Dochtermann3Armand Gerstenberger4Saiju Pyarajan5Eric J. Roseen6Million Veteran ProgramMarianna Gasperi7VA Puget Sound Health Care System (VAPSHCS)VA Puget Sound Health Care System (VAPSHCS)Department of Psychiatry, University of California San DiegoCenter for Data and Computational Sciences (C-DACS), VA Boston Healthcare System (VABHS)VA Puget Sound Health Care System (VAPSHCS)Center for Data and Computational Sciences (C-DACS), VA Boston Healthcare System (VABHS)Section of General Internal Medicine, Department of Medicine, Boston University Chobanian & Avedision School of Medicine and Boston Medical CenterVA Puget Sound Health Care System (VAPSHCS)Abstract This multi-ancestry meta-analysis of genome-wide association studies (GWAS) investigated the genetic factors underlying chronic back pain (CBP) in a sample from the Million Veteran Program comprised of 553,601 Veterans of African (19.2%), European (72.6%), and Hispanic (8.2%) ancestry. The results revealed novel (N = 67) and known (N = 20) genome-wide significant loci associated with CBP, with 43 independent variants replicating in a non-overlapping contemporary meta-GWAS of the spinal pain dorsalgia phenotype. The most significant novel variant was rs12533005 (chr7:114416000, p = 1.61 × 10−20, OR = 0.96 (95% CI: 0.95–0.97), EA = C, EAF = 0.39), in an intron of the FOXP2 gene. In silico functional characterization revealed enrichment in brain and pituitary tissues. Mendelian randomization analysis of 62 variants for CBP-MVP revealed 48 with causal links to dorsalgia. Notably, four genes (INPP5B, DRD2, HTT, SLC30A6) associated with these variants are targets of existing drugs. Our findings more than double the number of previously reported genetic predictors across all spinal pain phenotypes.https://doi.org/10.1038/s41467-024-55326-3 |
| spellingShingle | Ian B. Stanaway Pradeep Suri Niloofar Afari Daniel Dochtermann Armand Gerstenberger Saiju Pyarajan Eric J. Roseen Million Veteran Program Marianna Gasperi Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back pain Nature Communications |
| title | Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back pain |
| title_full | Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back pain |
| title_fullStr | Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back pain |
| title_full_unstemmed | Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back pain |
| title_short | Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back pain |
| title_sort | multi ancestry meta analysis of genome wide association studies discovers 67 new loci associated with chronic back pain |
| url | https://doi.org/10.1038/s41467-024-55326-3 |
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