Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Nat Genet. 2011 Jun;43(6):539-46. doi: 10.1038/ng.838. Epub 2011 May 22.
A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder.
一项联合全基因组关联和连锁研究用于鉴定导致囊性纤维化肺病严重程度变化的基因座。我们在 p.Phe508del 纯合子中发现了 EHF 和 APIP（chr11p13）附近的显著关联（P = 3.34×10(-8))（n = 1978）。该关联在来自独立家族研究的 p.Phe508del 纯合子中得到了复制（P = 0.006）（n = 557），三研究联合荟萃分析的 P 值为 1.49×10(-9)。来自基于家族的研究的 486 对同胞对的连锁分析确定了染色体 20q13.2 上的一个显著数量性状基因座（log(10)odds = 5.03）。我们的发现深入了解了囊性纤维化肺病严重程度变化的原因，并为这种限制生命的疾病提供了新的治疗靶点。
