deCODE Genetics/Amgen, Reykjavik, Iceland.
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Nat Genet. 2014 May;46(5):498-502. doi: 10.1038/ng.2957. Epub 2014 Apr 13.
Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P = 1.1 × 10(-11) (rs3204689).
骨关节炎是最常见的关节炎形式，也是老年人疼痛和残疾的主要原因。为了寻找导致手部骨关节炎风险的序列变异，我们对 2230 名冰岛患者的严重手部骨关节炎进行了全基因组关联研究（GWAS），使用通过全基因组测序鉴定的变体。我们在冰岛发现集中发现了两个与两个显著相关的基因座：在 ALDH1A2 基因中的 15q22（频率为 50.7%，优势比（OR）= 1.51，P = 3.99×10(-10))和 1p31（频率为 0.02%，OR = 50.6，P = 9.8×10(-10))。在携带 1p31 变异的个体中，有一个家族的多个成员具有与骨关节炎分离的风险等位基因。在荷兰和英国的复制集中证实了 ALDH1A2 基因内的变体，总体关联为 OR = 1.46 和 P = 1.1×10(-11)（rs3204689）。
