Prediction of ankylosing spondylitis in the HUNT study by a genetic risk score combining 110 single-nucleotide polymorphisms of genome-wide significance

Sina Rostami, Mari Hoff, Matthew A. Brown, Kristian Hveem, Oddgeir L. Holmen, Lars G. Fritsche, Vibeke Videm*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)
    183 Downloads (Pure)

    Abstract

    Objective. The genetic component of ankylosing spondylitis (AS) development is ~90%. Of the known heritability, ~20% is explained by HLA-B27, and 113 identified AS-associated single-nucleotide polymorphisms (SNP) account for ~7.4%. The objectives were to construct a weighted genetic risk score (wGRS) using currently known genome-wide susceptibility SNP, and to evaluate its predictive ability for AS in the Norwegian population-based Nord-Trøndelag Health Study (HUNT).

    Methods. AS cases (n = 164) and controls (n = 49,032) were from the second (1995-1997) and third (2006-2008) waves of the HUNT study, to which the entire adult population of the northern region of Trøndelag was invited. A wGRS based on 110 SNP weighted by published OR for AS was constructed, representing each person's carriage of all risk variants. Logistic regression models including the wGRS alone or in combination with HLA-B27 carrier state and other adjustment variables (sex, age, smoking, body mass index, and hypertension) were developed. Discrimination among models was compared using area under the curve (AUC).

    Results. The wGRS was associated with AS (OR 1.7, 95% CI 1.4-2.1), but showed low discrimination (AUC 0.62, 95% CI 0.58-0.67). HLA-B27 was significantly associated with AS (OR 50, 95% CI 32-81), showing high discrimination (AUC 0.88, 95% CI 0.85-0.90). Combining the wGRS and HLA-B27 improved prediction (AUC 0.90, 95% CI 0.87-0.92; p < 0.001 vs wGRS alone, p < 0.01 vs HLA-B27 alone). Further inclusion of adjustment variables gave a small improvement (AUC 0.91, 95% CI 0.89-0.94; p = 0.03).

    Conclusion. Prediction in a population-based setting based on all currently known AS susceptibility SNP was better than HLA-B27 carrier state alone, although the improvement was small and of uncertain clinical value.

    Original languageEnglish
    Pages (from-to)204-210
    Number of pages7
    JournalJournal of Rheumatology
    Volume47
    Issue number2
    Early online date1 Aug 2019
    DOIs
    Publication statusPublished - 1 Feb 2020

    Keywords

    • ANKYLOSING SPONDYLITIS
    • EPIDEMIOLOGY
    • GENETIC POLYMORPHISMS

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