Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting

M C T Slof-Op 't Landt; I Meulenbelt; M Bartels; E Suchiman; C M Middeldorp; J J Houwing-Duistermaat; J van Trier; E J Onkenhout; J M Vink; C E M van Beijsterveldt; M K Brandys; N Sanders; S Zipfel; W Herzog; B Herpertz-Dahlmann; K Klampfl; C Fleischhaker; A Zeeck; M de Zwaan; S Herpertz; S Ehrlich; R A H Adan; S Scherag; A Hinney; J Hebebrand; D I Boomsma; E F van Furth; P E Slagboom; Annemarie van Elburg

doi:10.1111/j.1601-183X.2010.00660.x

Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting

M C T Slof-Op 't Landt, I Meulenbelt, M Bartels, E Suchiman, C M Middeldorp, J J Houwing-Duistermaat, J van Trier, E J Onkenhout, J M Vink, C E M van Beijsterveldt, M K Brandys, N Sanders, S Zipfel, W Herzog, B Herpertz-Dahlmann, K Klampfl, C Fleischhaker, A Zeeck, M de Zwaan, S HerpertzS Ehrlich, R A H Adan, S Scherag, A Hinney, J Hebebrand, D I Boomsma, E F van Furth, P E Slagboom, Annemarie van Elburg

Experimental psychopathology

Leidschendam

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.

Original language	English
Article number	0
Pages (from-to)	236-43
Number of pages	8
Journal	Genes, Brain, and Behavior
Volume	10
Issue number	2
DOIs	https://doi.org/10.1111/j.1601-183X.2010.00660.x
Publication status	Published - 2011

Keywords

Adolescent
Adult
Alleles
Anorexia Nervosa
Body Weight
Bulimia Nervosa
Case-Control Studies
DNA
Data Interpretation, Statistical
Eating Disorders
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Male
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Tryptophan Hydroxylase
Young Adult

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Slof-Op 't Landt, M. C. T., Meulenbelt, I., Bartels, M., Suchiman, E., Middeldorp, C. M., Houwing-Duistermaat, J. J., van Trier, J., Onkenhout, E. J., Vink, J. M., van Beijsterveldt, C. E. M., Brandys, M. K., Sanders, N., Zipfel, S., Herzog, W., Herpertz-Dahlmann, B., Klampfl, K., Fleischhaker, C., Zeeck, A., de Zwaan, M., ... van Elburg, A. (2011). Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting. Genes, Brain, and Behavior, 10(2), 236-43. Article 0. https://doi.org/10.1111/j.1601-183X.2010.00660.x

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title = "Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting",

abstract = "Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.",

keywords = "Adolescent, Adult, Alleles, Anorexia Nervosa, Body Weight, Bulimia Nervosa, Case-Control Studies, DNA, Data Interpretation, Statistical, Eating Disorders, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Tryptophan Hydroxylase, Young Adult",

author = "{Slof-Op 't Landt}, {M C T} and I Meulenbelt and M Bartels and E Suchiman and Middeldorp, {C M} and Houwing-Duistermaat, {J J} and {van Trier}, J and Onkenhout, {E J} and Vink, {J M} and {van Beijsterveldt}, {C E M} and Brandys, {M K} and N Sanders and S Zipfel and W Herzog and B Herpertz-Dahlmann and K Klampfl and C Fleischhaker and A Zeeck and {de Zwaan}, M and S Herpertz and S Ehrlich and Adan, {R A H} and S Scherag and A Hinney and J Hebebrand and Boomsma, {D I} and {van Furth}, {E F} and Slagboom, {P E} and {van Elburg}, Annemarie",

note = "{\textcopyright} 2010 The Authors. Genes, Brain and Behavior {\textcopyright} 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.",

year = "2011",

doi = "10.1111/j.1601-183X.2010.00660.x",

language = "English",

volume = "10",

pages = "236--43",

journal = "Genes, Brain, and Behavior",

issn = "1601-1848",

publisher = "Wiley-Blackwell",

number = "2",

}

Slof-Op 't Landt, MCT, Meulenbelt, I, Bartels, M, Suchiman, E, Middeldorp, CM, Houwing-Duistermaat, JJ, van Trier, J, Onkenhout, EJ, Vink, JM, van Beijsterveldt, CEM, Brandys, MK, Sanders, N, Zipfel, S, Herzog, W, Herpertz-Dahlmann, B, Klampfl, K, Fleischhaker, C, Zeeck, A, de Zwaan, M, Herpertz, S, Ehrlich, S, Adan, RAH, Scherag, S, Hinney, A, Hebebrand, J, Boomsma, DI, van Furth, EF, Slagboom, PE & van Elburg, A 2011, 'Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting', Genes, Brain, and Behavior, vol. 10, no. 2, 0, pp. 236-43. https://doi.org/10.1111/j.1601-183X.2010.00660.x

TY - JOUR

T1 - Association study in eating disorders

T2 - TPH2 associates with anorexia nervosa and self-induced vomiting

AU - Slof-Op 't Landt, M C T

AU - Meulenbelt, I

AU - Bartels, M

AU - Suchiman, E

AU - Middeldorp, C M

AU - Houwing-Duistermaat, J J

AU - van Trier, J

AU - Onkenhout, E J

AU - Vink, J M

AU - van Beijsterveldt, C E M

AU - Brandys, M K

AU - Sanders, N

AU - Zipfel, S

AU - Herzog, W

AU - Herpertz-Dahlmann, B

AU - Klampfl, K

AU - Fleischhaker, C

AU - Zeeck, A

AU - de Zwaan, M

AU - Herpertz, S

AU - Ehrlich, S

AU - Adan, R A H

AU - Scherag, S

AU - Hinney, A

AU - Hebebrand, J

AU - Boomsma, D I

AU - van Furth, E F

AU - Slagboom, P E

AU - van Elburg, Annemarie

PY - 2011

Y1 - 2011

N2 - Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.

AB - Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.

KW - Adolescent

KW - Adult

KW - Alleles

KW - Anorexia Nervosa

KW - Body Weight

KW - Bulimia Nervosa

KW - Case-Control Studies

KW - DNA

KW - Data Interpretation, Statistical

KW - Eating Disorders

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Oligonucleotide Array Sequence Analysis

KW - Polymorphism, Single Nucleotide

KW - Tryptophan Hydroxylase

KW - Young Adult

U2 - 10.1111/j.1601-183X.2010.00660.x

DO - 10.1111/j.1601-183X.2010.00660.x

M3 - Article

C2 - 20946355

SN - 1601-1848

VL - 10

SP - 236

EP - 243

JO - Genes, Brain, and Behavior

JF - Genes, Brain, and Behavior

IS - 2

M1 - 0

ER -

Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting

Abstract

Keywords

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