TY - JOUR

T1 - Insight into the genetic architecture of back pain and its risk factors from a study of 509,000 individuals

AU - CHARGE Musculoskeletal Working Group

AU - Freidin, Maxim B.

AU - Tsepilov, Yakov A.

AU - Palmer, Melody

AU - Karssen, Lennart C.

AU - Suri, Pradeep

AU - Aulchenko, Yurii S.

AU - Williams, Frances M.K.

N1 - Publisher Copyright: © 2019 International Association for the Study of Pain.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Back pain (BP) is a common condition of major social importance and poorly understood pathogenesis. Combining data from the UK Biobank and CHARGE consortium cohorts allowed us to perform a very large genome-wide association study (total N = 509,070) and examine the genetic correlation and pleiotropy between BP and its clinical and psychosocial risk factors. We identified and replicated 3 BP-associated loci, including one novel region implicating SPOCK2/CHST3 genes. We provide evidence for pleiotropic effects of genetic factors underlying BP, height, and intervertebral disk problems. We also identified independent genetic correlations between BP and depression symptoms, neuroticism, sleep disturbance, overweight, and smoking. A significant enrichment for genes involved in the central nervous system and skeletal tissue development was observed. The study of pleiotropy and genetic correlations, supported by the pathway analysis, suggests at least 2 strong molecular axes of BP genesis, one related to structural/anatomical factors such as intervertebral disk problems and anthropometrics, and another related to the psychological component of pain perception and pain processing. These findings corroborate with the current biopsychosocial model as a paradigm for BP. Overall, the results demonstrate BP to have an extremely complex genetic architecture that overlaps with the genetic predisposition to its biopsychosocial risk factors. The work sheds light on pathways of relevance in the prevention and management of low BP.

AB - Back pain (BP) is a common condition of major social importance and poorly understood pathogenesis. Combining data from the UK Biobank and CHARGE consortium cohorts allowed us to perform a very large genome-wide association study (total N = 509,070) and examine the genetic correlation and pleiotropy between BP and its clinical and psychosocial risk factors. We identified and replicated 3 BP-associated loci, including one novel region implicating SPOCK2/CHST3 genes. We provide evidence for pleiotropic effects of genetic factors underlying BP, height, and intervertebral disk problems. We also identified independent genetic correlations between BP and depression symptoms, neuroticism, sleep disturbance, overweight, and smoking. A significant enrichment for genes involved in the central nervous system and skeletal tissue development was observed. The study of pleiotropy and genetic correlations, supported by the pathway analysis, suggests at least 2 strong molecular axes of BP genesis, one related to structural/anatomical factors such as intervertebral disk problems and anthropometrics, and another related to the psychological component of pain perception and pain processing. These findings corroborate with the current biopsychosocial model as a paradigm for BP. Overall, the results demonstrate BP to have an extremely complex genetic architecture that overlaps with the genetic predisposition to its biopsychosocial risk factors. The work sheds light on pathways of relevance in the prevention and management of low BP.

KW - Back pain

KW - Genome-wide association study

KW - CHARGE

KW - UK Biobank

KW - Pleiotropy

KW - GENOME-WIDE ASSOCIATION

KW - LUMBAR DISC DEGENERATION

KW - SPONDYLOEPIPHYSEAL DYSPLASIA

KW - OMANI-TYPE

KW - HERITABILITY

KW - GWAS

KW - POPULATION

KW - BURDEN

KW - IDENTIFICATION

KW - DISLOCATIONS

UR - http://www.scopus.com/inward/record.url?scp=85066418758&partnerID=8YFLogxK

U2 - 10.1097/j.pain.0000000000001514

DO - 10.1097/j.pain.0000000000001514

M3 - Article

C2 - 30747904

AN - SCOPUS:85066418758

VL - 160

SP - 1361

EP - 1373

JO - Pain

JF - Pain

SN - 0304-3959

IS - 6

ER -