Research perspectives in the etiology of congenital anorectal malformations using data of the International Consortium on Anorectal Malformations: evidence for risk factors across different populations.
OBJECTIVE
The recently established International Consortium on Anorectal Malformations aims to identify genetic and environmental risk factors in the etiology of syndromic and nonsyndromic anorectal malformations (ARM) by promoting collaboration through data sharing and combined research activities.


METHODS
The consortium attempts to recruit at least 1,000 ARM cases. DNA samples are collected from case-parent triads to identify genetic factors involved in ARM. Several genetic techniques will be applied, including SNP arrays, gene and whole exome sequencing, and a genome-wide association study. Questionnaires inquiring about circumstances before and during pregnancy will be used to obtain environmental risk factor data.


RESULTS
Currently, 701 ARM cases have been recruited throughout Europe. Clinical data are available from all cases, and DNA samples and questionnaire data mainly from the Dutch and German cases. Preliminary analyses on environmental risk factors in the Dutch and German cohort found associations between ARM and family history of ARM, fever during first trimester of pregnancy and maternal job exposure to cleaning agents and solvents.


CONCLUSIONS
First results show that both genetic and environmental factors may contribute to the multifactorial etiology of ARM. The International Consortium on Anorectal Malformations will provide possibilities to study and detect important genes and environmental risk factors for ARM, ultimately resulting in better genetic counseling, improved therapies, and primary prevention.
Wijers
Charlotte H W
CH
Department of Epidemiology, Biostatistics and HTA (133), Radboud University Nijmegen Medical Centre, P.O. box 9101, 6500 HB, Nijmegen, The Netherlands. L.Wijers@ebh.umcn.nl
de Blaauw
Ivo
I
Marcelis
Carlo L M
CL
Wijnen
Rene M H
RM
Brunner
Han
H
Midrio
Paola
P
Gamba
Piergiorgio
P
Clementi
Maurizio
M
Jenetzky
Ekkehart
E
Zwink
Nadine
N
Reutter
Heiko
H
Bartels
Enrika
E
Grasshoff-Derr
Sabine
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Holland-Cunz
Stefan
S
Hosie
Stuart
S
Märzheuser
Stefanie
S
Schmiedeke
Eberhard
E
Crétolle
Célia
C
Sarnacki
Sabine
S
Levitt
Marc A
MA
Knoers
Nine V A M
NV
Roeleveld
Nel
N
van Rooij
Iris A L M
IA
D001003:Anal Canal / Q000002:abnormalities*; D005060:Europe; D006801:Humans; D012007:Rectum / Q000002:abnormalities*; D012042:Registries; D012307:Risk Factors