Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
BACKGROUND
Fetal conditions can in principle be affected by the mother's genotype working through the prenatal environment.


RESULTS
Genotypes for 1536 SNPs in 357 cleft candidate genes were available from a previous analysis in which we focused on fetal gene effects. After data-cleaning, genotypes for 1315 SNPs in 334 autosomal genes were available for the current analysis of maternal gene effects. Two complementary statistical methods, TRIMM and HAPLIN, were used to detect multi-marker effects in population-based samples from Norway (562 case-parent and 592 control-parent triads) and Denmark (235 case-parent triads). We analyzed isolated cleft lip with or without cleft palate (iCL/P) and isolated cleft palate only (iCP) separately and assessed replication by looking for genes detected in both populations by both methods. In iCL/P, neither TRIMM nor HAPLIN detected more genes than expected by chance alone; furthermore, the selected genes were not replicated across the two methods. In iCP, however, FLNB was identified by both methods in both populations. Although HIC1 and ZNF189 did not fully satisfy our stringency criterion for replication, they were strongly associated with iCP in TRIMM analyses of the Norwegian triads.


CONCLUSIONS
Except for FLNB, HIC1 and ZNF189, maternal genes did not appear to influence the risk of clefting in our data. This is consistent with recent epidemiological findings showing no apparent difference between mother-to-offspring and father-to-offspring recurrence of clefts in these two populations. It is likely that fetal genes make the major genetic contribution to clefting risk in these populations, but we cannot rule out the possibility that maternal genes can affect risk through interactions with specific teratogens or fetal genes.
Jugessur
Astanand
A
Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
Shi
Min
M
Gjessing
Håkon Kristian
HK
Lie
Rolv Terje
RT
Wilcox
Allen James
AJ
Weinberg
Clarice Ring
CR
Christensen
Kaare
K
Boyles
Abee Lowman
AL
Daack-Hirsch
Sandra
S
Nguyen
Truc Trung
TT
Christiansen
Lene
L
Lidral
Andrew Carl
AC
Murray
Jeffrey Clark
JC
D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003285:Contractile Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D064448:Filamins; D005838:Genotype; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D009035:Mothers; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012537:Scandinavian and Nordic Countries; D012984:Software
D003285:Contractile Proteins; D004268:DNA-Binding Proteins; C578662:FLNB protein, human; D064448:Filamins; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D008840:Microfilament Proteins; C114474:ZNF189 protein, human