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Chunk #3 — RESULTS — Follow-up analyses (stage 2)

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Genome-wide association study identifies five loci associated with lung function.
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To validate potential associations with lung function, we selected 10 SNPs for further genotyping in additional studies of European ancestry (stage 2a, 32,184 individuals; Supplementary Table 2) and 30 SNPs for in silico follow-up (stage 2b; Supplementary Table 3). We obtained the in silico association results from the Health 2000 study (883 individuals) and from the CHARGE Consortium (21,209 individuals). Meta-analysis of the association results across stages 1, 2a and 2b showed five novel loci reaching genome-wide significance (P < 5 × 10−8): 2q35 in TNS1, 4q24 in GSTCD, 5q33 in HTR4, 6p21 in AGER and 15q23 in THSD4 (Table 2 and Fig. 2). A further locus, 6p21 in DAAM2, which was not selected for further genotyping follow-up in stage 2a, fell just below the threshold for genome-wide significance for association with FEV1/FVC after meta-analysis across stages 1 and 2b (rs2395730, P = 7.98 × 10−8; Supplementary Table 3 and Table 2).