Study Report

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Basic Info

Reference	Fan, J., 2010 PMID: 19308960
Citation	Fan, J., I. Ionita-Laza, et al. (2010). "Linkage disequilibrium mapping of the chromosome 6q21-22.31 bipolar I disorder susceptibility locus." Am J Med Genet B Neuropsychiatr Genet 153B(1): 29-37.
Disease Type	Bipolar I Disorder
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	530 cases, 534 controls, 256 nuclear families, 1,301 individuals
SNP/Region/Marker Size	3047 SNPs in initial stage and 151 SNPs for replication
Predominant Ethnicity	Caucasian
Population	American

Detail Info

Sample Diagnosis	DSM-IV, Diagnostic Interview for Genetic Studies
Sample Status	complete affected parent-proband trios for family sample.
Replication Size	622 cases, 1,181 controls
Technique	genotyping using two Oligo Pool Arrays (OPAs) by the Illumina BeadArray platform (San Diego, CA) at the Broad Institute. All SNPs in our follow-up tests were genotyped by an allelespecific primer extension of amplified products with detection by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy using the Sequenom iPLEX genotyping platform (San Diego, CA) at the Broad Institute.
Statistical Method	Genetic quality control analyses were performed using the PLINK software package. Single-marker association analyses were conducted using PLINK for the case-control sample, and FBAT for the family based sample. For gene-based analysis, The set-based test implemented in the PLINK software package was performed in case-control samples. The min-p test implemented in the FBAT software was performed in family-based samples.
Result Summary	SNP-wise and gene-based test results in the three samples provided convergent evidence for association with SLC22A16.

SNPs reported by this study for BD (count: 37)

SNP	Related Gene(s)	Risk Allele	Statistical Values	Author Comments	Result Category
rs9400393	SLC22A16	C	P-value = 0.00097 in STEP1 sample;	showed evidence of association in the STEP1 sample showed evidence of association in the STEP1 sample	Positive
rs9401352		G	P-value = 0.00025 in STEP1 sample;	showed evidence of association in the STEP1 sample showed evidence of association in the STEP1 sample	Positive
rs9491388		C	P-value = 0.0015 in STEP1 sample;	showed evidence of association in the STEP1 sample showed evidence of association in the STEP1 sample	Positive
rs1190053	PREP	A	P-value = 0.00046 in NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs10944288	HTR1E	G	P-value = 0.12 in STEP1 sample; P-value = 0.013 in NIMH sample; P-value = 0.0045 in STEP1 and NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs12198581		T	P-value = 0.00052 in NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs12213914	PREP	T	P-value = 0.00039 in NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs1204787	NT5DC1	C	P-value = 0.21 in STEP1 sample; P-value = 0.0035 in NIMH sample; P-value = 0.0032 in STEP1 and NIMH sample;	showed evidence of association in the NIMH sample and pooled...... showed evidence of association in the NIMH sample and pooled sample. More...	Positive
rs12153828	CEP85L	G	P-value = 0.039 in STEP2 sample;	showed evidence of association in the replication sample showed evidence of association in the replication sample	Positive
rs1339197	PTPRK	A	P-value = 0.0026 in NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs1688615		A	P-value = 0.015 in STEP2 sample;	showed evidence of association in the replication sample showed evidence of association in the replication sample	Positive
rs13191605		G	P-value = 0.00088 in NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs13196925	BVES	C	P-value = 0.002 in NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs17282486		G	P-value = 0.0037 in STEP1 sample; P-value = 0.29 in NIMH sample; P-value = 0.0052 in STEP1 and NIMH sample;	showed evidence of association in the STEP1 sample and poole...... showed evidence of association in the STEP1 sample and pooled sample More...	Positive
rs17447037	EPHA7	A	P-value = 0.0034 in STEP1 sample;	showed evidence of association in the STEP1 sample showed evidence of association in the STEP1 sample	Positive
rs17071713	SLC22A16	G	P-value = 0.0011 in STEP2 sample;	showed evidence of association in the replication sample showed evidence of association in the replication sample	Positive
rs17071722	SLC22A16	T	P-value = 0.0021 in NIMH sample; P-value = 0.02 in STEP2 sample;	showed evidence of association in the NIMH sample and replic...... showed evidence of association in the NIMH sample and replication sample More...	Positive
rs2428190	SLC22A16	C	P-value = 0.0017 in STEP2 sample;	showed evidence of association in the replication sample showed evidence of association in the replication sample	Positive
rs2496353	CEP85L BRD7P3	A	P-value = 0.0099 in STEP2 sample;	showed evidence of association in the replication sample showed evidence of association in the replication sample	Positive
rs2244924	SEC63	A	P-value = 0.0029 in STEP1 sample;	showed evidence of association in the STEP1 sample showed evidence of association in the STEP1 sample	Positive
rs2428168		T	P-value = 0.0027 in STEP1 sample;	showed evidence of association in the STEP1 sample showed evidence of association in the STEP1 sample	Positive
rs3823447	SLC22A16 DDO	A	P-value = 0.047 in STEP1 sample; P-value = 0.055 in NIMH sample; P-value = 0.0058 in STEP1 and NIMH sample;	showed evidence of association in the STEP1 sample and poole...... showed evidence of association in the STEP1 sample and pooled sample. More...	Positive
rs3798366	ROS1	A	P-value = 0.24 in STEP1 sample; P-value = 0.005 in NIMH sample; P-value = 0.0052 in STEP1 and NIMH sample;	showed evidence of association in the NIMH sample and pooled...... showed evidence of association in the NIMH sample and pooled sample. More...	Positive
rs3734381	CEP85L PLN	A	P-value = 0.03 in STEP2 sample;	showed evidence of association in the replication sample showed evidence of association in the replication sample	Positive
rs2892767	GJA1	T	P-value = 0.0017 in NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs6932749		A	P-value = 0.014 in STEP2 sample;	showed evidence of association in the replication sample showed evidence of association in the replication sample	Positive
rs6931341		A	P-value = 0.0003 in NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs6922074		T	P-value = 0.00021 in STEP1 sample;	showed evidence of association in the STEP1 sample showed evidence of association in the STEP1 sample	Positive
rs4946138	COL10A1 NT5DC1	G	P-value = 0.04 in STEP1 sample; P-value = 0.007 in NIMH sample; P-value = 0.0009 in STEP1 and NIMH sample;	showed evidence of association in STEP1 sample, NIMH sample ...... showed evidence of association in STEP1 sample, NIMH sample and pooled sample. More...	Positive
rs7768422	SLC22A16	G	P-value = 0.0053 in STEP2 sample;	showed evidence of association in the replication sample showed evidence of association in the replication sample	Positive
rs7765860	PKIB	C	P-value = 0.0016 in STEP1 sample;	showed evidence of association in the STEP1 sample showed evidence of association in the STEP1 sample	Positive
rs6938431	SLC22A16 DDO	T	P-value = 0.0000672 in STEP1 sample; P-value = 0.79 in NIMH sample; P-value = 0.0027 in STEP1 and NIMH sample; P-value = 0.04 in STEP2 sample;	showed evidence of association in STEP1 sample, pooled sampl...... showed evidence of association in STEP1 sample, pooled sample and replication sample. More...	Positive
rs6935739		G	P-value = 0.0013 in NIMH sample;	showed evidence of association in the NIMH sample showed evidence of association in the NIMH sample	Positive
rs871746		A	P-value = 0.04 in STEP1 sample; P-value = 0.013 in NIMH sample; P-value = 0.0014 in STEP1 and NIMH sample;	showed evidence of association in the STEP1 sample, NIMH sam...... showed evidence of association in the STEP1 sample, NIMH sample and pooled sample. More...	Positive
rs846950		C	P-value = 0.0026 in STEP1 sample;	showed evidence of association in the STEP1 sample showed evidence of association in the STEP1 sample	Positive
rs794854	CEP85L	C	P-value = 0.0076 in STEP1 sample; P-value = 0.033 in NIMH sample; P-value = 0.0007 in STEP1 and NIMH sample;	showed evidence of association in the STEP1 sample, NIMH sam...... showed evidence of association in the STEP1 sample, NIMH sample and pooled sample. More...	Positive
rs783419	AIM1	T	P-value = 0.17 in STEP1 sample; P-value = 0.009 in NIMH sample; P-value = 0.005 in STEP1 and NIMH sample;	showed evidence of association in the NIMH sample and pooled...... showed evidence of association in the NIMH sample and pooled sample. More...	Positive

Genes reported by this study for BD (count: 20)

Gene	Statistical Values/Author Comments	Result Category
BVES	For gene-based test, P-value = 0.22 in STEP1; P-value = 0.01 in NIMH; P-value = 0.016 in STEP1 and NIMH. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test.	Positive
SERINC1	For gene-based test, P-value = 0.017 in STEP1. nominally significant in STEP1 sample, but not survive Bonferroni correction test. nominally significant in STEP1 sample, but not survive Bonferroni correction test.	Positive
CEP85L	For gene-based test, P-value = 0.036 in STEP2. nominally significant in STEP2 sample, but not survive Bonferroni correction test. nominally significant in STEP2 sample, but not survive Bonferroni correction test.	Positive
FAM184A	For gene-based test, P-value = 0.043 in STEP1. nominally significant in STEP1 sample, but not survive Bonferroni correction test. nominally significant in STEP1 sample, but not survive Bonferroni correction test.	Positive
GJA1	For gene-based test, P-value = 0.24 in STEP1; P-value = 0.01 in NIMH; P-value = 0.017 in STEP1 and NIMH. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test.	Positive
NT5DC1	For gene-based test, P-value = 0.29 in STEP1; P-value = 0.02 in NIMH; P-value = 0.05 in STEP1 and NIMH. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test.	Positive
HSF2	For gene-based test, P-value = 0.007 in STEP1; P-value = 0.93 in NIMH; P-value = 0.043 in STEP1 and NIMH. nominally significant in STEP1 sample and pooled sample, but not survive Bonferroni correction test. nominally significant in STEP1 sample and pooled sample, but not survive Bonferroni correction test.	Positive
FAM26F	For gene-based test, P-value = 0.038 in STEP1. nominally significant in STEP1 sample, but not survive Bonferroni correction test. nominally significant in STEP1 sample, but not survive Bonferroni correction test.	Positive
POPDC3	For gene-based test, P-value = 0.021 in STEP1. nominally significant in STEP1 sample, but not survive Bonferroni correction test. nominally significant in STEP1 sample, but not survive Bonferroni correction test.	Positive
KPNA5	For gene-based test, P-value = 0.33 in STEP1; P-value = 0.02 in NIMH; P-value = 0.048 in STEP1 and NIMH. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test.	Positive
TSPYL4	For gene-based test, P-value = 0.041 in STEP1. nominally significant in STEP1 sample, but not survive Bonferroni correction test. nominally significant in STEP1 sample, but not survive Bonferroni correction test.	Positive
DDO	For gene-based test, P-value = 0.00079 in STEP1; P-value = 0.46 in NIMH; P-value = 0.0033 in STEP1 and NIMH. leading gene-based results, but not survive Bonferroni correction test. leading gene-based results, but not survive Bonferroni correction test.	Positive
SLC22A16	For gene-based test, P-value = 0.0013 in STEP1; P-value = 0.034 in NIMH; P-value = 0.00048 in STEP1 and NIMH; P-value = 0.03 in STEP2. nominally significant in all three samples nominally significant in all three samples	Positive
CNR1	For gene-based test, P-value = 0.063 in STEP1. non-significant in any samples. non-significant in any samples.	Negative
RFPL4B	For gene-based test, P-value = 0.036 in STEP1; P-value = 0.066 in NIMH; P-value = 0.017 in STEP1 and NIMH. nominally significant in STEP1 sample and pooled sample, but not survive Bonferroni correction test. nominally significant in STEP1 sample and pooled sample, but not survive Bonferroni correction test.	Positive
PREP	For gene-based test, P-value = 0.22 in STEP1; P-value = 0.0089 in NIMH; P-value = 0.014 in STEP1 and NIMH. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test.	Positive
PKIB	For gene-based test, P-value = 0.047 in STEP1. nominally significant in STEP1 sample, but not survive Bonferroni correction test. nominally significant in STEP1 sample, but not survive Bonferroni correction test.	Positive
SCML4	For gene-based test, P-value = 0.106 in STEP1. non-significant in any samples. non-significant in any samples.	Negative
FIG4	For gene-based test, P-value = 0.16 in STEP1; P-value = 0.03 in NIMH; P-value = 0.032 in STEP1 and NIMH. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test. nominally significant in NIMH sample and pooled sample, but not survive Bonferroni correction test.	Positive
SEC63	For gene-based test, P-value = 0.018 in STEP1. nominally significant in STEP1 sample, but not survive Bonferroni correction test. nominally significant in STEP1 sample, but not survive Bonferroni correction test.	Positive