TY - JOUR
T1 - Analysis of susceptibility loci for nonsyndromic orofacial clefting in a European trio sample
AU - Böhmer, Anne C
AU - Mangold, Elisabeth
AU - Tessmann, Peter
AU - Mossey, Peter A.
AU - Steegers-Theunissen, Regine P.
AU - Lindemans, Jan
AU - Bouwman-Both, Marieke
AU - Rubini, Michele
AU - Franceschelli, Paola
AU - Aiello, Vincenzo
AU - Peterlin, Borut
AU - Molloy, Anne M.
AU - Nöthen, Markus M.
AU - Knapp, Michael
AU - Ludwig, Kerstin U.
N1 - Copyright © 2013 Wiley Periodicals, Inc.
PY - 2013/10
Y1 - 2013/10
N2 - Nonsyndromic cleft lip with or without cleft palate (NSCL/P), the most common type of orofacial clefting, is one of the most frequent congenital defects. Based on epidemiological data, NSCL/P can be distinguished from nonsyndromic cleft palate only (NSCPO). Both phenotypes have a complex etiology and environmental and genetic factors are involved in their development. To date, genome-wide association studies have identified 12 genetic factors that increase the risk for NSCL/P in Europeans. Six of them have been independently replicated in samples derived from the same population. The aim of the present study was to replicate the remaining six NSCL/P risk loci in chromosomal regions 1p22.1, 1p36, 3p11.1, 8q21.3, 15q22.2, and 20q12 in a family-based sample of European descent. Each of the top-associated SNPs (single nucleotide polymorphisms) was genotyped in 343 NSCL/P and 266 NSCPO nuclear trios. Single-marker association analysis in the NSCL/P sample showed a significant association with SNP rs742071 (1p36, Pcorrected ?=?3.74?×?10(-3) ), which is located in the intronic region of PAX7, a gene known to be functionally implicated in craniofacial development. Two additional loci, 1p22.1 and 20q12, were nominally significant, but did not withstand correction for multiple testing. There was no evidence that the NSCL/P risk alleles contribute to the etiology of NSCPO, further supporting that these two subtypes of orofacial clefting are primarily etiologically distinct. © 2013 Wiley Periodicals, Inc.
AB - Nonsyndromic cleft lip with or without cleft palate (NSCL/P), the most common type of orofacial clefting, is one of the most frequent congenital defects. Based on epidemiological data, NSCL/P can be distinguished from nonsyndromic cleft palate only (NSCPO). Both phenotypes have a complex etiology and environmental and genetic factors are involved in their development. To date, genome-wide association studies have identified 12 genetic factors that increase the risk for NSCL/P in Europeans. Six of them have been independently replicated in samples derived from the same population. The aim of the present study was to replicate the remaining six NSCL/P risk loci in chromosomal regions 1p22.1, 1p36, 3p11.1, 8q21.3, 15q22.2, and 20q12 in a family-based sample of European descent. Each of the top-associated SNPs (single nucleotide polymorphisms) was genotyped in 343 NSCL/P and 266 NSCPO nuclear trios. Single-marker association analysis in the NSCL/P sample showed a significant association with SNP rs742071 (1p36, Pcorrected ?=?3.74?×?10(-3) ), which is located in the intronic region of PAX7, a gene known to be functionally implicated in craniofacial development. Two additional loci, 1p22.1 and 20q12, were nominally significant, but did not withstand correction for multiple testing. There was no evidence that the NSCL/P risk alleles contribute to the etiology of NSCPO, further supporting that these two subtypes of orofacial clefting are primarily etiologically distinct. © 2013 Wiley Periodicals, Inc.
U2 - 10.1002/ajmg.a.36141
DO - 10.1002/ajmg.a.36141
M3 - Article
C2 - 24038802
SN - 1552-4825
VL - 161
SP - 2545
EP - 2549
JO - American Journal of Medical Genetics Part A
JF - American Journal of Medical Genetics Part A
IS - 10
ER -