Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.

<h4>Background</h4>Fetal conditions can in principle be affected by the mother's genotype working through the prenatal environment.<h4>Methodology/principal findings</h4>Genotypes for 1536 SNPs in 357 cleft candidate genes were available from a previous analysis in which...

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Autores principales:	Astanand Jugessur, Min Shi, Håkon Kristian Gjessing, Rolv Terje Lie, Allen James Wilcox, Clarice Ring Weinberg, Kaare Christensen, Abee Lowman Boyles, Sandra Daack-Hirsch, Truc Trung Nguyen, Lene Christiansen, Andrew Carl Lidral, Jeffrey Clark Murray
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b19ebe906fe94b6886ec7cf42395e08b
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spelling	oai:doaj.org-article:b19ebe906fe94b6886ec7cf42395e08b2021-12-02T20:20:13ZMaternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.1932-620310.1371/journal.pone.0011493https://doaj.org/article/b19ebe906fe94b6886ec7cf42395e08b2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20634891/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Fetal conditions can in principle be affected by the mother's genotype working through the prenatal environment.<h4>Methodology/principal findings</h4>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.<h4>Conclusion/significance</h4>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.Astanand JugessurMin ShiHåkon Kristian GjessingRolv Terje LieAllen James WilcoxClarice Ring WeinbergKaare ChristensenAbee Lowman BoylesSandra Daack-HirschTruc Trung NguyenLene ChristiansenAndrew Carl LidralJeffrey Clark MurrayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11493 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Astanand Jugessur Min Shi Håkon Kristian Gjessing Rolv Terje Lie Allen James Wilcox Clarice Ring Weinberg Kaare Christensen Abee Lowman Boyles Sandra Daack-Hirsch Truc Trung Nguyen Lene Christiansen Andrew Carl Lidral Jeffrey Clark Murray Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
description	<h4>Background</h4>Fetal conditions can in principle be affected by the mother's genotype working through the prenatal environment.<h4>Methodology/principal findings</h4>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.<h4>Conclusion/significance</h4>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.
format	article
author	Astanand Jugessur Min Shi Håkon Kristian Gjessing Rolv Terje Lie Allen James Wilcox Clarice Ring Weinberg Kaare Christensen Abee Lowman Boyles Sandra Daack-Hirsch Truc Trung Nguyen Lene Christiansen Andrew Carl Lidral Jeffrey Clark Murray
author_facet	Astanand Jugessur Min Shi Håkon Kristian Gjessing Rolv Terje Lie Allen James Wilcox Clarice Ring Weinberg Kaare Christensen Abee Lowman Boyles Sandra Daack-Hirsch Truc Trung Nguyen Lene Christiansen Andrew Carl Lidral Jeffrey Clark Murray
author_sort	Astanand Jugessur
title	Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
title_short	Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
title_full	Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
title_fullStr	Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
title_full_unstemmed	Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
title_sort	maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from scandinavia.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/b19ebe906fe94b6886ec7cf42395e08b
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Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.

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