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Chunk #4 — Results — Variant selection for replication

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A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.
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For further analysis we selected the twenty top ranked genetic variants (including rs971074) for replication (Figure S1). These included those genetic variants in the discovery phase that achieved a p-value of ≤1×10−5 (12 variants) as well as nonsynonymous variants that achieved a p-value of ≤1×10−4 (5 additional variants). We also included variants that achieved a p-value of ≤5×10−7 when restricting the analysis to a specific UADT cancer site (1 variant), or heavy drinkers (1 variant) (Table 1). Only one variant from each high r2 group (r2>0.8) was included. We additionally included the non-synonymous ADH1B variant, rs1229984, that has been previously associated with UADT cancers [14] but not genotyped or tagged by a proxy variant on the HumanHap300 BeadChip. The association between the top ranked genetic variants selected for replication and UADT cancer was not sensitive to adjustment for population structure using principal component analysis, or exclusion generic controls (Table S2). rs1573496 was genotyped for replication as a proxy for rs971074 (r2 = 1.00) and rs698 for rs1789924 (r2>0.97) due to availability of Taqman assays. A TaqMan assay for rs12827056 could not be designed and no highly correlated (r2>0.95) proxy genetic variant was available, hence further investigation was not possible.