RESUMO
Lumbar disc herniation (LDH) is common and often debilitating. Microdiscectomy of herniated lumbar discs (LDHsurg) is performed on the most severe cases to resolve the resulting sciatica. Here we perform a genome-wide association study on 4,748 LDHsurg cases and 282,590 population controls and discover 37 highly correlated markers associating with LDHsurg at 8q24.21 (between CCDC26 and GSDMC), represented by rs6651255[C] (OR=0.81; P=5.6 × 10-12) with a stronger effect among younger patients than older. As rs6651255[C] also associates with height, we performed a Mendelian randomization analysis using height polygenic risk scores as instruments to estimate the effect of height on LDHsurg risk, and found that the marker's association with LDHsurg is much greater than predicted by its effect on height. In light of presented findings, we speculate that the effect of rs6651255 on LDHsurg is driven by susceptibility to developing severe and persistent sciatica upon LDH.
Assuntos
Cromossomos Humanos Par 8/genética , Predisposição Genética para Doença , Variação Genética , Degeneração do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/genética , Vértebras Lombares/patologia , Ciática/genética , Adulto , Sequência de Bases , Estatura/genética , Demografia , Feminino , Loci Gênicos , Humanos , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Fatores de RiscoRESUMO
OBJECTIVE: The objective of this study was to produce a standardized medical risk-related history (MRRH) in order to identify the medically compromised patient (MCP) attending the general dental practitioner for treatment, to develop such a history (EMRRH), and to validate it in dental practices in 10 European countries. STUDY DESIGN: The Dutch MRRH, adapted to allow for legal and cultural differences of the participating countries was introduced. After consensus and repeated testing, the questionnaire was validated. In this last phase, 1000 patients older than 18 attending dental practices were selected, 100 per country; 994 medical histories were suitable for statistical analysis. Validation was carried out by a physician accustomed to making preoperative assessments, including the ASA risk classification. RESULTS: Mean specificity per country was 99.1 and per EMRRH item was 99.0. Mean sensitivity per country was 93.2 and per item was 93.7. Cohen's kappa for the countries involved was 0.81 to 0.98 and for subsequent questions was 0.81 to 0.97. CONCLUSION: The EMRRH was found to be valid in the detection of medically compromised patients in 10 European countries.