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Chunk #13 — Method — Association Analyses

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Family-based genome-wide association scan of attention-deficit/hyperactivity disorder.
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We used PLINK 14 to conduct transmission disequilibrium tests. To control for multiple comparisons we adopted the conservative recommendation of Dudbridge et al and Pe’er et al 15, 16 and considered p-values less than 5.0E-08 to be statistically significant genome-wide. We also examined 43 candidate genes (N=3,603 SNPs) of interest based upon those examined in Neale et al 5 or based upon the recent literature: ADRA1A, ADRA1B, ADRA2A, ADRA2C, ADRB2, ADRBK2, ARRB1, BDNF, CDH13, CHRNA4, COMT, CSNK1E, DBH, DDC, DRD1, DRD2, DRD3, DRD4, FADS1, FADS2, HES1, HTR1B, HTR1E, HTR2A, HTR2C, HTR3B, MAOA, MAOB, NFIL3, NR4A2, PER1, PER2, SLC18A2, SLC6A1, SLC6A2, SLC6A3, SLC6A4, SLC9A9, SNAP25, STX1A, SYT1, TPH1, and TPH2. The analytic unit of interest for these tests was the gene, and we utilized the set-based tests provided in PLINK. 14 The set-based tests estimate the significance of each SNP and then calculate the average chi-squared statistic for the most significant SNPs per gene. Permutation tests were used to obtain empirical significance levels of the gene-based test, while accounting for the number of tests conducted within gene and the lack of