SUPPLEMENTARY MATERIAL

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Supplementary Digital Information
1. Materials and Methods
Participants
A total of 1,421 participants were included in the study: 673 patients with BPD and 748
controls. The patients were recruited at four German academic institutions: Department of
Psychosomatic Medicine, Central Institute of Mental Health, Mannheim (252); Department of
Psychiatry and Psychotherapy, University Medical Center Mainz (214); Department of
Psychiatry, Charité, Berlin (179); Department of Psychiatry, Ludwig Maximilians University
Munich (28). Patients were included if the following criteria were met: age ranging from 16 to
65, Central European ancestry, lifetime diagnosis of BPD (according to DSM-IV). 748
unscreened controls were recruited via blood donation in the area of Mannheim.
Clinical assessment
Diagnoses of BPD criteria (for DSM-IV) were established from clinical interviews. At the
Central Institute of Mental Health assessment of BPD criteria was based on the German
versions of the IPDE Loranger. The three other centers used the SCID-II to assess DSM-IV
criteria of BPD First. In all of the centers the diagnostic interviews were carried out by
experienced and trained raters.
In all centers, diagnoses of bipolar disorders were assessed with clinical interviews. While
different diagnostic interviews were used across the study sites (SCID-I, (8); MINI, (9); DIA-X,
(10)), all were carried out by experienced and trained raters.
Table S1. Demographic characteristics
Cases
(n = 673)
Controls
(n = 748)
Age (Mean ± standard
deviation)
29.8 ± 8.7 44.5 ± 12.7
Gender (% female) 90.9% 55%
1

at-Test; bFisher’s exact test.
Table S1b: Gender distribution of patient samples per study
site:
Study site Males Females
Mannheim 0.4% 99.6%
Mainz 21.0% 79.0%
Munich 0.0% 100.0%
Berlin 8.4% 91.6%
2

Genotyping
Individuals with call rates of >90% had been filtered out prior to the present analyses.
Markers were filtered using the following criteria: call rate > 0.9; minor allele frequency >
0.01; conformance with Hardy-Weinberg-Equilibrium (p>0.001). Finally, genotyping quality
was assessed via visual inspection of the clusterplots of selected SNPs. After quality control,
the final sample comprised 673 BPD cases and 748 controls. All five SNPs of interest
obtained call rates of > 0.99. No evidence of differential missingness was obtained for any of
the six markers.
2. Results
BPD and comorbid BD
A total of n=31 cases met diagnostic criteria for bipolar disorders (4.6 %). Following the
exclusion of BPD cases with co-morbid BD, the p-value increased (preduced sample=0.062).
However, this increase was most likely due to the decreased sample size rather than the
exclusion of patients with mania, as indicated by a Monte-Carlo approach which randomly
excluded 31 cases 10,000 times.
A formal test of heterogeneity of effects in the two genders obtained a marginally significant
result of p=0.07 rs1006737. Although this result did not fulfill our stringent criteria for
significance, it was marginally significant and thus suggestive of a sex difference.
3

Table S2A: Results in female subsample
SNPaGene Minor allele genotype
counts
cases
genotype
counts
controls
ORb (95%-CIc) P-Value
(2-tailed)
rs10994336 ANK3 T 1/74/536 2/42/367 1.12 (0.77–1.63) 0.56
rs10994397 ANK3 T 2/76/533 2/44/365 1.13 (0.78–1.63) 0.52
rs12576775 ODZ4 G 16/166/427 14/104/291 1.01 (0.79–1.28) 0.94
rs1006737dCACNA1C A 73/262/276 34/162/215 1.29 (1.06–1.56) 0.01
rs4765913dCACNA1C A 33/202/376 7/128/276 1.34 (1.07–1.69) 0.01
aSNP
bOR = odds ratio
cCI = confidence interval
dMarkers ar in LD (r²=0.46, D’=0.90)
Table S2B: Results in male subsample
SNPaGene Minor allele genotype
counts
cases
genotype
counts
controls
ORb (95%-CIc) P-Value
(2-tailed)
rs10994336 ANK3 T 0/12/50 1/34/302 1.90 (0.96–
3.76)
0.06
rs10994397 ANK3 T 0/13/49 1/38/298 1.86 (0.96–
3.58)
0.06
rs12576775 ODZ4 G 0/14/48 12/87/238 0.65 (0.36– 0.15

1.17)
rs1006737dCACNA1C A 4/26/32 29/152/156 0.83 (0.54–
1.28)
0.39
rs4765913dCACNA1C A 1/24/37 11/124/202 0.96 (0.60–
1.53)
0.86
aSNP
bOR = odds ratio
cCI = confidence interval
dMarkers ar in LD (r²=0.46, D’=0.90)

3. References
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