TY - JOUR
T1 - Multi-ancestry meta-analysis of genome-wide association studies discovers 67 new loci associated with chronic back pain
AU - Million Veteran Program
AU - Stanaway, Ian B.
AU - Suri, Pradeep
AU - Afari, Niloofar
AU - Dochtermann, Daniel
AU - Gerstenberger, Armand
AU - Pyarajan, Saiju
AU - Rosen, Eric J.
AU - Gasperi, Marianna
N1 - Publisher Copyright:
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85218477686&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-55326-3
DO - 10.1038/s41467-024-55326-3
M3 - Article
C2 - 39934103
AN - SCOPUS:85218477686
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1525
ER -