Other Variant Report

Basic Info

Name	5HTTLPR
Type	microsatellite
Location	promoter
Related Gene	SLC6A4
No. of Study	41 (Positive: 12; Negative 29; Trend: 0)
Overlap with SZ?	YES
Overlap with MDD?	YES

Variant related studies (count: 41)

Reference	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
Mellerup, E.,2001	short/long		Association analysis:allele P-value > 0.05, genotype P-value > 0.05	No significant association was observed in BD.	Negative
Vincze, I., N., 2008			Genotypic P-value = 0.628; Allelic P-value = 0.93	There was no difference in genotype or allele frequencies be..... More There was no difference in genotype or allele frequencies between controls and overall BD patients and BD subgroups for 5-HTTLPR polymorphism. Less	Negative
Bellivier, F., 1998 (b)			Test between 'ss' and other genotypes pooled: g vs. i: X² = 4.68, d.f. = 1, P-value = 0.03; g vs. h: X² =0.49, d.f. = 1, P-value = 0.48; h vs. i: X² = 0.83, d.f. = 1, P-value = 0.36; g + h vs. i: X² = 4.21, d.f. = 1, P-value = 0.04; j vs. l: X² = 1.43, d.f. = 1, P-value = 0.23; k v.s l: X² = 0.23, d.f. = 1, P-value = 0.63.	For the 5-HTTLPR polymorphism, homozygosity for the 's' alle..... More For the 5-HTTLPR polymorphism, homozygosity for the 's' allele was significantly more frequent in bipolar patients than in controls whereas there was no difference between bipolar patients and controls for allele distribution. Less	Positive
Van Den Bogaert, A., 2006 (b)	del/ins		genotypic P-value = 0.6, OR (95% CI)=1.33 (0.89-1.97) for del/ins genotype, OR (95% CI)=1.02 (0.58-1.80) for del/del genotype; allelic P-value = 0.6	Genotypic and allelic marker analysis showed no evidence for..... More Genotypic and allelic marker analysis showed no evidence for association with BP. Less	Negative
Mohammadi, S., 2015			genotypic P-value=0.037, X²=6.62 in co-dominant model, genotypic P-value=0.98, X²=0 in dominant model, genotypic P-value=0.017, X²=5.65, OR (95%CI, p)=1.79 (1.1-2.88, p=0.018) in recessive model; allelic P-value=0.11, X²=2.5	In recessive model (SS vs. LL + LS) the frequency of SS geno..... More In recessive model (SS vs. LL + LS) the frequency of SS genotype was significantly higher in patients (39.5%) than that in controls (26.8%, p = 0.017) that was associated with 1.79-fold increased risk of BID. Also, the presence of S allele increased the risk of adult-onset BID by 1.76-fold. Less	Positive
Hauser, J.,2003	short/long		Association analysis: bipolar vs. control, X² = 8.945, d.f. = 2, P-value = 0.011 for genotypes, P-value = 0.003 for alleles.	Significant associations were found in BPD patients.	Positive
Meira-Lima, I.,2005	long/short		Chi square test:genotype:(1)between cases and controls, X²=10.4, 2 df, P-value = 0.005, (2)l/l vs.l/s + s/s among patients and controls, X²=0.22, 1 df, P-value = 0.6;allele:X²=4.35, 1 df, P-value = 0.03 and allele s:OR = 0.92, 95% CI 0.64-1.32 under a logistic regression model	Significant associations were found between BPD patients and..... More Significant associations were found between BPD patients and controls. Less	Positive
Neves, F. S., 2008			Genotypic X²=0.5 (df=2), P-value = 0.78	There were no significant differences between bipolar patien..... More There were no significant differences between bipolar patients and healthy controls in genotypic frequencies. Less	Negative
Ikeda, M., 2006			allelic P-value = 0.452, genotypic P-value = 0.339, Power calculation GRR=1.65	No associations of 5HTTLPR with BP was found.	Negative
Wang, T. Y., 2013	S/L		P-value=0.01, X²=8.86; P-value=0.01, X²=10.18 for male; P-value=0.71, X²=0.68 for female; 5-HTTLPR S+: P-value=0.03, OR=1.71 for all BP-I, P-value=0.01, OR=2.43 for male BP-I, P-value=0.70, OR=1.17 for female BP-I, P-value=0.003, OR=2.04 for all BP-II, P-value=0.007, OR=2.53 for male BP-II, P-value=0.37, OR=1.43 for female BP-II	The distribution of the 5-HTTLPR genotype was significantly ..... More The distribution of the 5-HTTLPR genotype was significantly different between the BP-I, BP-II, and the control groups, and a higher percentage of 5-HTTLPR S+ genotypes was found in the BP-I and BP-II groups. Further analysis of the gender difference revealed that the significantly different distribution of the 5-HTTLPR genotype was only in men. It showed an association between SLC6A4 and BP-II. A gender-specific association of the 5-HTTLPR polymorphisms and the risk for BP-I and BP-II was also found in the regression model. Less	Positive
Serretti, A.,2002	short/long		Association analysis:chi square test, genotype P-value > 0.05, allele P-value > 0.05	No significant association was observed in BD.	Negative
Alaerts, M.,2009	short/long		Allelic association P-value = 0.41;Genotypic association P-value = 0.40	no significant associations were found	Negative
Hoehe, M. R., 1998	S/L		two-tailed P-value=0.549, X²=0.360, df=1 for BD patients, P-value=0.483, X²=0.491, df=1 for combined patients	the frequency of the 5' regulatory variant alleles did not d..... More the frequency of the 5' regulatory variant alleles did not differ between controls and combined patients or BD patients Less	Negative
Rotondo, A.,2002	short/long		Association analysis:genotype, chi square(2df)=6.63, P-value = 0.04, allele, chi square(1df)=5.45, P-value = 0.02	Significant associations were found in BPD patients.	Positive
Soronen, P.,2011	La/StLg		For BD, allele, P-value = 0.8896	No significant association was observed.	Negative
Esterling, L. E., 1998			TDT P-value=0.70 of ASMI, P-value=0.75 of ASMII	By using the TDT, no significant evidence for association be..... More By using the TDT, no significant evidence for association between the 5-HTTLPR alleles and bipolar disorder was detected under either the stringent ASM I classification or the broader ASM II criteria, which includes recurrent unipolar illness. Less	Negative
Furlong, R. A., 1998 (a)			P-value>0.05; meta-analysis of Promoter alleles: test of association, P-value=0.049, X²=3.86, 1df, OR (95% CI)=1.21 (1.00-1.45) of 2 vs.1 in the bipolar sample; P-value=0.014, X²=6, 1df, OR (95% CI)=1.22 (1.04-1.42) of 2 vs. 1 in the combined sample; meta-analysis of Promoter genotypes: Test of association, P-value=0.1, X²=4.56, 2df, OR (95% CI)=1.48 (1.02-1.53) of 2 2vs.1 1, OR (95% CI)=1.09 (0.81-1.48) of 1 2vs.1 1 in the bipolar sample; P-value=0.035, X²=6.73, 2df, OR (95% CI)=1.48 (1.02-1.53) of 2 2vs.1 1, OR (95% CI)=1.10 (0.85-1.41) of 1 2vs.1 1 in the combined sample.	Allele and genotype frequencies were not significantly diffe..... More Allele and genotype frequencies were not significantly different from the controls in either of the patient groups or in the combined unipolar and bipolar group. We found a significant association of promoter allele 2 with disease risk in the bipolar , unipolar and the combined bipolar + unipolar groups. Less	Positive
Ospina-Duque, J.,2000	short/long		Association analysis:chi sauqre test, allele , chi square=0.57, df=1, P-value = 0.45;genotype, chi square=2.47, df=2, P-value = 0.29	No significant association was observed in BD.	Negative
Oliveira, J. R.,2000	short/long		Association analysis:chi sauqre test, allele, chi square=1.584, 1df, P-value = 0.21	No significant association was observed in BD.	Negative
Rees, M., 1997			genotypic P-value=0.60, X²=1.01, 2 d.f., allelic P-value=0.35, X²=0.89, 1 d.f.,	There was no significant difference between genotype or alle..... More There was no significant difference between genotype or allele distributions in bipolars and controls. Less	Negative
Mynett-Johnson, L.,2000	short/long		Assocaition analysis:TDT, Independent trios(N=92), chi square=3.88, 1df, P-value = 0.049;all trios(N=106), chi square=2.18, 1df, P-value = 0.14	Significant association was found in BPD patients.	Positive
Kirov, G.,1999(c)	long/short		TDT:chi2 = 0.39, 1 df, P = 0.53	No significant differences were found in bipolar groups.	Negative
Gutierrez, B., 1998			for allele distribution: X²=0.08 df=1, P-value=0.778; for genotype distribution: X²=1.26, df=2, P-value=0.531	No significant differences in allele or genotype distributio..... More No significant differences in allele or genotype distribution were found. In our study, when genotype distribution was analyzed considering s dominant, no significant differences were found between subjects and controls, although s variant was found to occur more frequently in bipolar patients. Less	Negative
Serretti, A.,2002	long/short		Association analysis:TDT, P-value = 0.831	No significant association was observed.	Negative
Mick, E.,2009	short/long	short	TDT:OR=0.87, 95%CI=0.63-1.19, X²=0.8, P-value = 0.38	We failed to identify significant associations with this can..... More We failed to identify significant associations with this candidate. Less	Negative
Jiang HY, 2013	S/L		P-value=0.005, pooled OR=1.10 for S allele, 95% CI=1.03-1.17; heterogeneity P-value=0.406 and I²= 4.1	Results of the meta-analysis showed that there wasa signific..... More Results of the meta-analysis showed that there wasa significant association between 5-HTTLPR and BD risk, and the S-allele of the variant could increase risk of BD. For all studies, no significantheterogeneity was observed. The analysis revealed that removal of any of the included samples at a time made no significant influence on the association between 5-HTTLPR and BD. Less	Positive
Masoliver, E., 2006	l/s		P-value = NS (not significant) of allele frequencies and distribution of genotypes in individuals with bipolar disorder, unipolar disorder and controls	No significant differences in the genotype distribution were..... More No significant differences in the genotype distribution were observed. Less	Negative
Mundo, E.,2000	short/long		Association analysis:TDT, chi square=0.692, df=1, P-value = 0.4054	No significant association was observed in BD.	Negative
Mohamed Saini, S., 2013	long/short		SS genotypic P-value=0.315, OR=2.03, 95% CI=0.50-8.17, X²=0.47, df=1 in Malays; P-value=0.310, OR=0.44, 95% CI=0.21-0.92, X²=2.86, df=1 in Indians; P-value=0.220, OR=4.67, 95% CI=0.69-7.58, X²=1.52, df=1 in overall; S allelic P-value=0.780, OR=0.76, 95% CI=0.27-2.09, X²=0.29, df=1 in Malays; P-value=0.836, OR=0.33, 95% CI=0.02-4.74, X²=0.04, df=1 in Indians; P-value=0.670, OR=0.82, 95% CI=0.34-2.01, X²=0.18, df=1 in overall	It shows no significant association between the 5-HTTLPR hom..... More It shows no significant association between the 5-HTTLPR homozygous ss genotype and bipolar disorder in the pooled subjects as well as after stratification into ethnic subgroups, the Malays and Indians. Similarly, comparison across all three ethnic subgroups and pooled subjects of the 5-HTTLPR s allele between bipolar disorder and controls yielded no significant differences. Less	Negative
Sun, H. S., 2004	s/l		Fisher's exact test, allelic P-value = 0.41, genotypic P-value = 0.71	No association can be obtained between any of the SLC6A4 gen..... More No association can be obtained between any of the SLC6A4 gene polymorphisms and BPD. Less	Negative
Cho, H. J.,2005	short/long		meta-analysis:the pooled estimate using the fixed-effects model (OR 1.12, 95% CI 1.03-1.21, P-value = 0.007)	Significant associations were found in BP.	Positive
Shah, M. P.,2009	short/long		1.vACC:Effect for genotype (F(1, 74)=12.78, p=0.0006).The interaction between genotype and emotional face type(F(2, 74)=1.89, p=0.16).ll individuals compared to s allele carriers across emotional face types: response to fearful (F(1, 74)=15.2, p=0.0002), happy (F(1, 74)=5.25, p=0.025), and neutral faces (F(1, 74)=6.55, p=0.013).For diagnosis:F(1, 74)=6.58, p=0.012.For interaction between diagnosis and emotional face type:F(2, 74)=1.89, p=0.47.For activation in the HC group compared to the BD group in response to fearful (F(1, 74)=7.85, p=0.007), happy faces (F(1, 74)=4.8, p=0.032), neutral faces (F(1, 74)=1.75, p=0.19).2.Amygdala: main effect of hemisphere as left amygdala activation compared to right amygdala activation to all face types (F(1, 370)=10.2, p=0.0015).main effect of emotion as activation to fearful faces compared to activation to both happy and neutral faces (F(2, 370)=9.25, p=0.0001).	During fear and happy face processing, vACC activation was s..... More During fear and happy face processing, vACC activation was significantly lower in the BD compared to the HC group, and in s carriers compared to ll individuals within both the HC and BD groups, such that BD s carriers exhibited the greatest magnitude of vACC dysfunction. No significant differences were detected in amygdala activation. Less	Positive
Kunugi, H.,1997(a)	long/short		chi square tests:all P-value >0.05	No significant differences were found in bipolar groups.	Negative
Lin, C. I.,2010	short/long		multiple regression:BP-I vs. control group, OR(95%CI)=2.303(0.480-11.052), P-value = 0.297;BP-II vs. control group, OR(95%CI)=0.578(0.128-2.615), P-value = 0.476;BP-I vs. BP-II, OR(95%CI)=2.189(0.695-6.893), P-value = 0.181.For Novelty Seeking:BP-I vs. control group, OR(95%CI)=1.126(0.889-1.427), P-value = 0.324;BP-II vs. control group, OR(95%CI)=1.097(0.913-1.318), P-value = 0.324;BP-I vs. BP-II, OR(95%CI)=0.866(0.742-1.011), P-value = 0.068	No significant association was observed.	Negative
Mansour, H. A.,2005	L/S		Pittsburgh BD1 sample:trends test for case-control analysis, P-value = 0.884;TDT T/NT=18/24;STEP-BD sample:trends test for case-control analysis, P-value = Pittsburgh BD1 sample:trends test for case-control analysis, P-value = 0.884;TDT T/NT=18/24	No significant association was observed.	Negative
Mendes de Oliveira, J. R., 1998			P-value=0.822, X²=2(1 d.f.)	In addition, no significant difference at the 5% critical le..... More In addition, no significant difference at the 5% critical level was observed when only bipolar and normal controls were compared. Less	Negative
Lasky-Su, J. A.,2005	short/long		meta-analysis:the combined OR =1.13(z=3.22, P-value = 0.001, CI (OR): [1.05-1.22])	Significant associations were found in BD.	Positive
Mendlewicz, J., 2004			X² (df=2)=0.1, P-value = 0.95 for genotypes; X² (df=1)=0.07, P-value = 0.8 for alleles distributions	No significant differences emerged.	Negative
Piccardi, M. P.,2002	short/long		Association analysis:TDT, allele long, T/NT=56/47, chi square=0.78, P-value = 0.37	No significant association was observed in BD.	Negative
Lotrich, F. E., 2004			S allele with bipolar disorder, X² (df=1)=3.25, P-value < 0.08 in the European/American populations; X² (df=1)=3.66, P-value < 0.06 in the two Asian studies;	With the studies combined, there was a slight trend for an a..... More With the studies combined, there was a slight trend for an association of the S allele with bipolar disorder. Less	Negative
Kumar, H. B., 2007			not given in the original text	no significant difference in genotype or allele frequencies ..... More no significant difference in genotype or allele frequencies was observed in the BPAD groups as compared with control group Less	Negative

Overlap with SZ from cross-disorder studies (count: 3)

Reference	Statistical Result	Description	Result Category
Mendes de Oliveira, J. R., 1998	no P-value	Although it will be important to extend the present analysis in a larger sample, our preliminary results suggest that the 5-HTTLPR does not seem to play a major role in the genetics of schizophrenic disorder at least in this group of Brazilian psychiatric patients.	Negative
Ikeda, M., 2006	allelic P-value = 0.441, genotypic P-value = 0.214, Power calculation GRR=1.46	No associations of 5HTTLPR with SCZ was found.	Negative
Serretti, A.,2002	Association analysis:chi square test, genotype P-value > 0.05, allele P-value > 0.05	No significant association was observed in SZ.	Negative

Overlap with MDD from cross-disorder studies (count: 12)

Reference	Statistical Result	Description	Result Category
Hoehe, M. R., 1998	two-tailed P-value=0.649, X²=0.207, df=1 for MDD patients, P-value=0.483, X²=0.491, df=1 for combined patients	the frequency of the 5' regulatory variant alleles did not differ between controls and combined patients or MDD patients	Negative
Hauser, J.,2003	Association analysis:unipolar vs. control, X² = 11.760, d.f. = 2, P-value = 0.003 for genotypes; P-value = 0.001 for alleles.	Significant associations were found in MDD.	Positive
Mellerup, E.,2001	Association analysis:allele P-value > 0.05, genotype P-value > 0.05	No significant association was observed in MDD.	Negative
Lotrich, F. E., 2004	X² (df=1)=2.53, P-value = 0.11 for overall. X² (df=1)=0.89, P-value = 0.35 in the Asian population	The S allele frequency was increased in MDD in most studies, but the trend was non-significant.	Negative
Mendlewicz, J., 2004	X² (df=2)=0.62, P-value = 0.73 for genotypes; X² (df=1)=0.46, P-value = 0.49 for alleles distributions	No significant differences emerged.	Negative
Kunugi, H.,1997(a)	chi square tests:all P-value >0.05	No significant differences were found in unipolar groups.	Negative
Soronen, P.,2011	For MDD, allele, P-value = 0.0006;For Mood, allele, P-value = 0.0068, OR=1.243, P-value(perm)=0.304	Significant associations were found in MDD.	Positive
Oliveira, J. R.,2000	Association analysis:chi sauqre test, allele, chi square=1.143, 1df, P-value = 0.29	No significant association was observed in MDD.	Negative
Lasky-Su, J. A.,2005	meta-analysis:OR=1.05, z=1.07, P-value = 0.28, CI (OR): [0.96-1.14]	No significant associations were found in MDD.	Negative
Rees, M., 1997	frequency of the deleted allele: P-value = 0.054, X²=3.72, 1 d.f., frequency in the outpatient sample: P-value=0.91, X²=0.01, 1 d.f., the lithium clinic sample: P-value=0.010; OR=1.89, CI=1.16-3.06, X²=6.71, 1 d.f.	Comparing the combined sample of unipolars against controls there is a reduction in the frequency of the deleted allele that approaches significance. Comparison of the allele frequencies in the two unipolar samples shows that the frequency in the outpatient sample is very close to the control frequency whereas the lithium clinic sample shows a significant decrease in frequency of the deleted allele compared with controls.	Positive
Serretti, A.,2002	Association analysis:chi square test, genotype P-value > 0.05, allele P-value > 0.05	No significant association was observed in MDD.	Negative
Furlong, R. A., 1998 (a)	P-value>0.05; meta-analysis of Promoter alleles: test of association, P-value=0.042, X²=4.1, 1df, OR (95% CI)=1.23 (1.01-1.52) of 2 vs.1 in the unipolar sample; P-value=0.014, X²=6, 1df, OR (95% CI)=1.22 (1.04-1.42) of 2 vs. 1 in the combined sample; meta-analysis of Promoter genotypes: Test of association, P-value=0.076, X²=5.15, 2df, OR (95% CI)=1.55 (1.04-2.32) of 2 2vs.1 1, OR (95% CI)=1.06 (0.76-1.49) of 1 2vs.1 1 in the unipolar sample; P-value=0.035, X²=6.73, 2df, OR (95% CI)=1.48 (1.02-1.53) of 2 2vs.1 1, OR (95% CI)=1.10 (0.85-1.41) of 1 2vs.1 1 in the combined sample.	Allele and genotype frequencies were not significantly different from the controls in either of the patient groups or in the combined unipolar and bipolar group. We found a significant association of promoter allele 2 with disease risk in the bipolar , unipolar and the combined bipolar + unipolar groups.	Positive