SUPPLEMENT
SUPPLEMENTAL METHODS
Family-Based Association Analysis
We performed family-based association analysis in FBAT(Horvath et al, 2001) using the
subsets of families identified by the OSA for the chromosomes with the strongest OSA
LOD scores: chromosomes 3, 8, 12, and X. The null hypothesis of linkage but no
association was tested using the -e flag, which computes the test statistic through use of
the empirical variance, because the sample contains multiple nuclear families in some
pedigrees and multiple affected individuals in these nuclear families, and the markers are
in an area of known linkage. Multiallelic tests were performed using additive, dominant
and recessive models. Haplotype association analysis was also performed using the –e
flag which works in a similar fashion to the –e flag in fbat.
SUPPLEMENTAL RESULTS
Family-Based Association Analysis
Results for FBAT analyses using either additive, dominant or recessive models for the
chromosome 3 subset conditioned on linkage to chromosome 17q12-21, the chromosome
12 subset conditioned for linkage to 2q37, the chromosome 12 subset conditioned for
linkage to 17q12-21, and the chromosome 23 subset conditioned on linkage to 2q37 are
given in Supplemental Table 1. No nominally significant associations were observed in
analysis of chromosome 8. The most significant nominal p value for any SNP under any
model was rs1488403 on chromosome 3 (additive, dominant and recessive) with FBAT p
values < 0.01. However, these results were not robustly significant after Bonferroni
correction (p=6x10-5) for multiple testing. No even nominally significant results were
found using the haplotypes association method.
Supplement Table 1: Results of FBAT analysis using additive, dominant and recessive
models
Chr
Marker
Mb
Allele
3.62
1
Allele
No.
frequency Families
P*
Gene Region†
0.008
LRRN1
Additive Model
3
rs1488403
0.387
19
(220 kb)
3
rs262180
68.43
1
0.497
21
0.009
FAM19A1
12_2
rs1064951
118.89
1
0.405
13
0.008
KDM2B
12_17 rs1846629
33.02
1
0.825
11
0.022
SYT10
(500 kb)
23
rs1869588
5.88
1
0.36
11
0.048
microRNA 651
(19 kb)
Dominant Model
3
rs1488403
3.62
1
0.387
18
0.007
LRRN1
(220 kb)
3
D3S1601
189.08
11
0.074
10
0.013
LOC100129725
SPG14
CLDN1
12_2
rs1064951
118.89
2
0.595
10
0.006
KDM2B
12_2
D12S2078
124.94
6
0.334
11
0.018
IBD2
12_17
rs187991
57.01
2
0.564
11
0.011
SLC16A7
(120 kb)
rs1869588
23
5.88
1
0.36
11
0.048
microRNA 651
(19 kb)
Recessive Model
rs1488403
3
3.62
2
0.613
18
0.007
LRRN1
(220 kb)
12_2
rs1064951
118.89
1
0.405
10
0.006
KDM2B
12_17
rs187991
57.01
1
0.436
11
0.011
SLC16A7
(120 kb)
23
rs1869588
5.88
1
0.36
11
0.048
microRNA 651
(19 kb)
* After correction for multiple testing, none of these p values were significant.
† Genes listed with a distance in parentheses are the nearest gene to the tested SNP, the
distance given is the distance from the SNP to the 5’/3’ end of the gene.