Comprehensive Analysis of MRI-Phenotypes Provides New Insights into Lumbar Disc Degeneration for Genetic Studies

Abstract

Introduction For the past two decades, numerous genetic association studies addressing lumbar disc degeneration (LDD) have been performed, but few of them can be replicated. The possible reasons could be the phenotype definition of LDD was highly variable between studies and level-specific variations were not addressed. As such, this study addressed the relationship between MRI features of the discs at different lumbar levels to explore the etiology of LDD; thereby, providing new insights and measurements for genetic studies. Materials and Methods Sagittal T2-weighted MRI of the lumbar spine was assessed in a population sample of 2,952 Southern Chinese (mean age, 41.1 years; range, 15.0-65.4 years; 40.7% males; 59.3% females). Loss of disc signal intensity, disc bulges/extrusions, Schmorl nodes, high-intensity zones, and bone marrow changes were assessed on imaging. Subject demographics, environmental, and lifestyle factors were also evaluated. Pairwised polychoric correlations between phenotypes in all five lumbar discs were performed using R v3.01 Heritability was estimated by Genome-wide Complex Trait Analysis (GCTA) using genotype data to identify phenotypes shared common genetic factors. Local regressions were performed between conditions and risk factors, such as age and body mass index, to distinguish the relationship between phenotypes and environmental factors. Phenotypes which were highly correlated and shared common genetic factors were grouped to form a new measurement. Results Analyses suggested distinct genetic etiologies for the upper (L1-L2) versus lower regions (L3-S1).Estimation of heritability showed the upper (L1-L2) and lower regions (L3-S1) of the lumbar spine shared common genetics factors, respectively; but upper and lower regions could present independent genetic features. Regression between phenotype and age denoted that age-related condition was restricted to lower regions while the upper region suggests developmental characters. By combining highly correlated MRI phenotypes in the upper and lower regions separately, two composite scores were generated: a degenerative score (DgS) (represents agerelated disc changes) and a developmental score (DvS) (represents congenital variations). Conclusion Based on one of the largest population-based MRI studies of LDD, comprehensive analyses of MRI phenotypes provided new insights into its etiology. Our study proposes a novel phenotype scoring system to assess disc changes on MRI. This scoring system can be used as the basis to promote a standardization of phenotype delineation, maximizing the potential of replication and meta-analysis studies of genetic risk factors for LDD. Disclosure of Interest None declared