Objective: The genetic predisposition to ankylosing spondylitis (AS) has been most widely studied in cohorts with European ancestry. However, within Europe, disease prevalence is higher in Sweden. Given this, we aimed to characterize known AS susceptibility variants in a homogeneous Swedish data set, assessing reproducibility and direction of effect.

Method: The power to detect association within an existing Swedish targeted sequencing study (381 controls; 310 AS cases) was examined, and a set of published associations (n = 151) was intersected with available genotypes. Association to disease was calculated using logistic regression accounting for population structure, and HLA-B27 status was determined with direct polymerase chain reaction genotyping.

Results: The cases were found to be 92.3% HLA-B27 positive, with the data set showing ≥ 80% predictive power to replicate associations, with odds ratios ≥ 1.6 over a range of allele frequencies (0.1–0.7). Thirty-four markers, representing 23 gene loci, were available for investigation. The replicated variants tagged MICA and IL23R loci (p < 1.47 × 10⁻³), with variable direction of effect noted for gene loci IL1R1 and MST1.

Conclusion: The Swedish data set successfully replicated both major histocompatibility complex (MHC) and non-MHC loci, and revealed a different replication pattern compared to discovery data sets. This was possibly due to population demographics, including HLA-B27 frequency and measured comorbidities.

目的：强直性脊柱炎 (AS) 的遗传易感性在具有欧洲血统的人群中得到了最广泛的研究。然而，在欧洲，瑞典的疾病流行率更高。鉴于此，我们旨在在同质瑞典数据集中表征已知的 AS 易感性变体，评估可重复性和效果方向。

方法：检查现有瑞典靶向测序研究（381 名对照；310 名 AS 病例）中检测关联的能力，并将一组已发表的关联（n = 151）与可用的基因型相交。使用考虑人口结构的逻辑回归计算与疾病的关联，并使用直接聚合酶链反应基因分型确定HLA-B27状态。

结果：发现这些病例的HLA-B27阳性率为 92.3%，数据集显示 ≥ 80% 的复制关联预测能力，在一系列等位基因频率 (0.1–0.7) 上的优势比 ≥ 1.6。代表 23 个基因位点的 34 个标记可用于研究。复制的变体标记了MICA和IL23R基因座 (p < 1.47 × 10 ^-3 )，注意到基因座IL1R1和MST1的可变作用方向。

结论：瑞典数据集成功复制了主要组织相容性复合体 (MHC) 和非 MHC 基因座，与发现数据集相比，揭示了不同的复制模式。这可能是由于人口统计数据，包括HLA-B27频率和测量的合并症。