Study Report

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Basic Info

Reference	Mick, E., 2008 PMID: 18361424
Citation	Mick, E., J. W. Kim, et al. (2008). "Family based association study of pediatric bipolar disorder and the dopamine transporter gene (SLC6A3)." Am J Med Genet B Neuropsychiatr Genet 147B(7): 1182-1185.
Disease Type	Bipolar I Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	170 bipolar-I affected offspring triads were drawn from 522 individuals with 2 parents in 332 nuclear families recruited for genetic studies.
SNP/Region/Marker Size	28 SNPs
Predominant Ethnicity	Caucasian
Population	European
Gender	124 males, 94 females for bipolar offspring
Age Group	Children : Bipolar offspring mean age=12.9 (SD=5.3) years old,

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	All children met criteria for DSM-IV bipolar I disorder. The mean age at onset was 7.3, SD=4.8 years of age and the clinical presentation was chronic (3.5 SD=3.6 years duration), rapid cycling (18.4 SD=53.5 episodes), and functionally impairing (GAF score of 41.0 SD=6.2). In addition, 85% (N=145) of children with bipolar-I disorder also met criteria for ADHD. In addition, 45 affected:unaffected parent pairs were identified. Parents with bipolar-I disorder had an average age at onset of 23.1 SD=10.9 years and duration of 5.9 SD=7.8 years of illness.
Statistical Method	For the Transmission Disequilibrium Test (TDT) we used the PLINK (v1.0) software package. Odds ratios and 95% confidence intervals, however are calculated using only the basic TDT. Multiple permutation (n=100,000) was used to calculate empirical P values and to correct for the number of statistical comparisons conducted. Findings were considered statistically significant at permuted P<0.05.
Result Summary	Results indicated nominally positive association for 4 SNPs (rs40184, rs11133767, rs3776512, and rs464049), but only rs40184 survived correction formultiple statistical comparisons (P=0.038). These data provide suggestive evidence supporting a role for SLC6A3 in the etiology of pediatric bipolar disorder.

SNPs reported by this study for BD (count: 26)

SNP	Related Gene(s)	Risk Allele	Statistical Values	Author Comments	Result Category
rs11133767	SLC6A3	T	TDT X²(df=1)=4.02, P-value = 0.045, OR (95% CI)=1.22(0.89-1.68)	Results indicated nominally positive association for this SN...... Results indicated nominally positive association for this SNP. More...	Positive
rs11564773	SLC6A3	C	TDT X²(df=1)=0.02, P-value = 0.999, OR (95% CI)=1.22(0.66-2.28)		Negative
rs11564767	SLC6A3	T	TDT X²(df=1)=0.02, P-value = 0.999, OR (95% CI)=1(0.55-1.83)		Negative
rs12516758	SLC6A3	C	TDT X²(df=1)=0.83, P-value = 0.412, OR (95% CI)=1.25(0.86-1.83)		Negative
rs11737901	SLC6A3	T	TDT X²(df=1)=1.14, P-value = 0.331, OR (95% CI)=0.92(0.67-1.25)		Negative
rs2617605	SLC6A3	C	TDT X²(df=1)=0.56, P-value = 0.499, OR (95% CI)=1.09(0.78-1.51)		Negative
rs246995	SLC6A3	G	TDT X²(df=1)=1.01, P-value = 0.359, OR (95% CI)=1.19(0.85-1.67)		Negative
rs27048	SLC6A3	T	TDT X²(df=1)=1.18, P-value = 0.303, OR (95% CI)=0.81(0.60-1.10)		Negative
rs2652510	SLC6A3	C	TDT X²(df=1)=0.32, P-value = 0.595, OR (95% CI)=1.06(0.78-1.45)		Negative
rs27074	SLC6A3	T	TDT X²(df=1)=2.32, P-value = 0.166, OR (95% CI)=1.73(1.02-2.92)		Negative
rs27072	SLC6A3	T	TDT X²(df=1)=2.03, P-value = 0.18, OR (95% CI)=1.44(0.97-2.14)		Negative
rs2735917	SLC6A3	A	TDT X²(df=1)=0.08, P-value = 0.89, OR (95% CI)=0.89(0.47-1.72)		Negative
rs2963238	SLC6A3	T	TDT X²(df=1)=0.32, P-value = 0.593, OR (95% CI)=1.08(0.79-1.46)		Negative
rs2975292	SLC6A3	C	TDT X²(df=1)=0.32, P-value = 0.599, OR (95% CI)=1.07(0.78-1.46)		Negative
rs37022	SLC6A3	T	TDT X²(df=1)=1.14, P-value = 0.309, OR (95% CI)=1.06(0.72-1.57)		Negative
rs3756450	SLC6A3	G	TDT X²(df=1)=0.71, P-value = 0.459, OR (95% CI)=0.8(0.51-1.27)		Negative
rs3776512	SLC6A3	A	TDT X²(df=1)=6.42, P-value = 0.012, OR (95% CI)=1.5(1.02-2.20)	Results indicated nominally positive association for this SN...... Results indicated nominally positive association for this SNP. More...	Positive
rs3863145	SLC6A3	A	TDT X²(df=1)=2.13, P-value = 0.146, OR (95% CI)=1.06(0.76-1.49)		Negative
rs40184	SLC6A3	T	TDT X²(df=1)=9.39, P-value = 0.003, OR (95% CI)=1.52(1.12-2.06)	Results indicated nominally positive association for four SN...... Results indicated nominally positive association for four SNPs, but only rs41084 survived correction for multiple statistical comparisons. More...	Positive
rs403636	SLC6A3	A	TDT X²(df=1)=0.04, P-value = 0.928, OR (95% CI)=0.92(0.61-1.38)		Negative
rs456082	SLC6A3	G	TDT X²(df=1)=0.07, P-value = 0.856, OR (95% CI)=1.06(0.73-1.53)		Negative
rs460000	SLC6A3	T	TDT X²(df=1)=0.44, P-value = 0.529, OR (95% CI)=1.13(0.78-1.61)		Negative
rs464049	SLC6A3	G	TDT X²(df=1)=5.79, P-value = 0.021, OR (95% CI)=1.33(0.99-1.78)	Results indicated nominally positive association for this SN...... Results indicated nominally positive association for this SNP. More...	Positive
rs464528	SLC6A3	T	TDT X²(df=1)=0.44, P-value = 0.537, OR (95% CI)=1.13(0.78-1.61)		Negative
rs4975646	SLC6A3	A	TDT X²(df=1)=1.29, P-value = 0.293, OR (95% CI)=0.9(0.66-1.23)		Negative
rs6350	SLC6A3	A	TDT X²(df=1)=1, P-value = 0.412, OR (95% CI)=1.33(0.72-2.46)		Negative

Other variants reported by this study for BD (count: 1)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs10064525	SLC6A3			G	TDT X²(df=1)=0.06, P-value = 0.888, OR (95% CI)=0.86(0.50-1.48)		Negative

Genes reported by this study for BD (count: 1)