Comprehensive Analysis of MRI‐phenotypes Provides New Insights into Lumbar Disc Degeneration for Genetic Studies

Abstract

INTRODUCTION: Numerous genetic associa‐ tion studies addressing lumbar disc degen‐ eration (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 ad‐ dressed. 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. 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 to 65.4 years; 40.7% males; 59.3% females). Loss of disc signal intensity, disc bulges/extrusions, Schmorl's nodes, high‐intensity zones, and bone marrow changes were assessed on imaging. Subject demographics, environ‐ mental and lifestyle factors were also eval‐ uated. Polychoric correlations, heritability estimations and local regression statistical analyses were performed. RESULTS: Analyses suggested distinct genet‐ ic etiologies for the upper (L1‐L2) versus lower regions (L3‐S1). Age‐related condition was restricted to lower regions while the upper region suggests congenital. By com‐ bining highly‐correlated MRI‐phenotypes in the upper and lower regions separately, two composite scores were generated: a degen‐ erative score (DgS) (represents age‐related disc changes) and a developmental score (DvS) (represents congenital variations). DISCUSSION: Based on one of the largest population‐based studies of LDD, compre‐ hensive analyses of MRI‐phenotypes pro‐ vided new insights into its etiology. Our study proposes a novel phenotype scoring system. This scoring system can be used as the basis to promote a standardization of phenotype delineation, maximizing the po‐ tential of replication and meta‐analysis studies of genetic risk factors for LDD.