Suppl_document1.doc
Figure S1:
Illustrates linkage disequilibrium across the 20 gene loci which contained more than 1 marker
genotyped in this sample. Haploview (Barrett et al, Bioinformatics, 2005, PMID:15297300) was used
to generate LD plots displaying the r-squared values (expressed as a percentage) between marker
pairs. Note that Figure S1 (O) shows the two genes SLC6A2 and CES1, which were sufficiently
close to be analysed as one unit (i.e. no within-locus interactions were tested).
Figure S2:
QQ plot for the chi-squared test on all interaction pairs (N=9262)
Figure S3:
Illustration of the distribution of chi-square statistics, ordered by the distance between the pair of
markers being examined (syntenic markers only). Apparent 'columns' of points indicate a gene-pair,
with relatively similar intermarker distances. Non-parametric Spearman rank correlations were
calculated for all points, and after excluding the gene pairs with intermarker distances in the 10^8
base pair range.
Figure S4
Chi-square statistics (A) or empirical p-values (B) plotted against Odds Ratio estimates (y-axis on
a log scale). Bootstrap confidence intervals are indicated for the Odds Ratio. The images illustrate
that large Odds Ratio estimates often have very wide confidence intervals. The red lines in (B)
indicate the odds ratio and p-value thresholds for display in Table 2 (main text).
Figure S5:
Plot of the relationship between the case-only estimated interaction odds ratio and the interaction
parameter estimated from conditional logistic regression using a case-psuedo-control design.
Suppl_tables.xls
Table S1:
Details of the markers examined in the present study: Gene, Chromosome, Marker name, base pair
position (hg18), relative position to gene, prior information supporting possible role in ADHD
aetiology, journal references.
Table S2:
Minor allele frequencies of the markers in parents (column 5) and probands (column 6)
Table S3:
Full results of all 9269 interaction tests (including sparse tables) using the case-only design (red)
and the case-pseudo-control design (purple).
Column headings:
Gene1 - gene tagged by first marker
Marker1 - first marker name
Chr1 - chromosome of first marker
Pos1 - base pair position (hg18) of first marker
Gene2 - gene tagged by second marker
Marker2 - second marker name
Chr2 - chromosome of second marker
Pos2 - base pair position (hg18) of second marker
1_1_count - 2x2 table count of allele 1 (marker 1) with allele 1 (marker 2)
1_2_count - idem for allele 1 with allele 2
2_1_count - idem for allele 2 with allele 1
2_2_count - idem for allele 2 with allele 2
OR - odds ratio estimate from contingency table
OR_95%_l - lower bootstrap 95% confidence bound
OR_95%_u - upper bootstrap 95% confidence bound
Chi2 - chi-square (1 d.f.) statistic from contingency table
p - p-value from Pearson chi-square test on the contingency table
p_emp_summ - empirical p-value (see main text)
OR_rescaled - odds ratio estimate scaled to be > 1
OR_rescaled_95%_l - confidence interval lower bound rescaled
OR_rescaled_95%_u - confidence interval upper bound rescaled
N - number of affected individuals contributing to contingency table
%N - percentage of the total affected individuals contributing
mA-mA count - count of minor allele (marker 1) - minor allele (marker 2) pairs
mA-mA_F - relative frequency of minor allele - minor allele pairs
OR_marker1 – conditional logistic regression main effect odds ratio of marker 1
OR_marker2 – cond. LR main effect odds ratio of marker 2
OR_interaction – cond. LR interaction (additive x additive) odds ratio
LRT_Chi – likelihood ratio test chi-square statistic
LRT_p-value – p-value for LRT chi-square test (1 degree of freedom)
R^2_partial – pseudo-R2 for main-effect-only model
R^2_full – pseudo-R2 for model with main effects and interaction (additive x additive)
Note 1: NA indicates that a zero cell count was observed in the contingency table; these pairs were
discarded.
Note 2: markers with minor allele frequency < 0.1 in founders have "_LOWMAF" appended to the
marker name.