Supplementary material for paper:

“Genomewide pharmacogenomic analysis of response to treatment with anti-psychotics”

Content

  1. Calculation of q-values

2.  Table S1. Q-values for combined drug effects GWAS

3.  Table S2. Tested candidate genes plus number of SNPs


1. CALCULATION OF THE FDR AND Q-VALUES

FDRs can be estimated in multiple ways and many standard computer packages (e.g. R, SAS) have such estimation procedures implemented. The first approach is to estimate the FDR for a chosen threshold P-value t. If the m P-values are denoted pi, i = 1…m, this can be done using the formula:

Thus, the FDR is estimated by dividing the estimated number of false discoveries (is number of tests times the probability t of rejecting a marker without effect) by the total number of significant markers (i.e. total number of P-values smaller than t) that includes the false and true positives. To avoid arbitrary choices, each of the observed P-values can be used as a threshold P-value t. The resulting FDR statistics are then called q-values 1;2.

Reference List

(1) Storey J, Tibshirani R. Statistical significance for genome-wide studies. Proceedings of the National Academy of Sciences 2003;100:9440-9445.

(2) Storey J. The positive false discovery rate: A Bayesian interpretation and the q-value. Annals of Statistics 2003;31:2013-2035.

Table S1. Number of GWAS q-values below various thresholds for the six PANSS scales, effects of all drugs combined (CATIE Phase I data only)

By PANSS scale / q-value threshold
0.1 / 0.25 / 0.5 / 0.75 / 0.95
Total symptoms / 0 / 0 / 0 / 0 / 0
Positive / 0 / 0 / 0 / 0 / 1
Negative / 0 / 0 / 0 / 0 / 0
Disorganization / 0 / 0 / 0 / 1 / 7
Excitement / 0 / 0 / 0 / 4 / 10
Emotional distress / 0 / 0 / 0 / 0 / 0
Sum / 0 / 0 / 0 / 5 / 18

Table S2. Tested candidate genes plus number of SNPs

Drug response
Gene / # SNPs
ABCB1 (MDR1) / 75
AOX1 / 31
BDNF / 72
CHAT / 16
CNR1 / 101
COMT / 95
CYP1A2 / 2
CYP2C19 / 2
CYP2D6 / 0
CYP3A4 / 0
CYP3A43 / 5
CYP3A5 / 2
CYP3A7 / 3
DRD1 / 116
DRD2 / 128
DRD3 / 82
DRD4 / 26
FMO1 / 0
FMO2 / 0
FMO3 / 29
FMO4 / 134
FMO5 / 101
GNB3 / 0
GRM3 / 36
HRH1 / 58
HRH2 / 20
HTR1A / 58
HTR1F / 48
HTR2A / 176
HTR2C / 11
MTHFR / 4
NEF3 / 123
NRG1 / 174
RGS4 / 140
SLC6A2 / 25
SLC6A4 / 8
TPH1 / 120
UGT1A3 / 0
UGT1A4 / 11
2032