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WRIGHT, Fred A; STRUG, Lisa J; COREY, Mary; DORFMAN, Ruslan; GODDARD, Katrina; GREEN, Deanna; KENT, Jack W; LANGE, Ethan M; LEE, Seunggeun; WEILI LI; JINGCHUN LUO; MAYHEW, Gregory M; DOSHI, Vishal K; NAUGHTON, Kathleen M; PACE, Rhonda G; PARE, Peter; ROMMENS, Johanna M; SANDFORD, Andrew; STONEBRAKER, Jaclyn R; WEI SUN; TAYLOR, Chelsea; VANSCOY, Lori L; FEI ZOU; COMMANDER, Clayton W; BLANGERO, John; ZIELENSKI, Julian; O'NEAL, Wanda K; DRUMM, Mitchell L; DURIE, Peter R; KNOWLES, Michael R; CUTTING, Garry R; BLACKMAN, Scott M; LEI SUN; BERTHIAUME, Yves; CUTLER, David; COJOCARU, Andreea; COLLACO, J. Michael
Nature genetics, 06/2011, Letnik: 43, Številka: 6Journal Article
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.
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