Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24

Stefanie Birnbaum; Kerstin U. Ludwig; Heiko Reutter; Stefan Herms; Michael Steffens; Michele Rubini; Carlotta Baluardo; Melissa Ferrian; Nilma Almeida de Assis; Margrieta A. Alblas; Sandra Barth; Jan Freudenberg; Carola Lauster; Guel Schmidt; Martin Scheer; Bert Braumann; Stefaan J. Berge; Rudolf H. Reich; Franziska Schiefke; Alexander Hemprich; Simone Poetzsch; Regine P. Steegers-Theunissen; Bernd Poetzsch; Susanne Moebus; Bernhard Horsthemke; Franz-Josef Kramer; Thomas F. Wienker; Peter A. Mossey; Peter Propping; Sven Cichon; Per Hoffmann; Michael Knapp; Markus M. Noethen; Elisabeth Mangold

doi:10.1038/ng.333

Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24

Stefanie Birnbaum, Kerstin U. Ludwig, Heiko Reutter, Stefan Herms, Michael Steffens, Michele Rubini, Carlotta Baluardo, Melissa Ferrian, Nilma Almeida de Assis, Margrieta A. Alblas, Sandra Barth, Jan Freudenberg, Carola Lauster, Guel Schmidt, Martin Scheer, Bert Braumann, Stefaan J. Berge, Rudolf H. Reich, Franziska Schiefke, Alexander HemprichSimone Poetzsch, Regine P. Steegers-Theunissen, Bernd Poetzsch, Susanne Moebus, Bernhard Horsthemke, Franz-Josef Kramer, Thomas F. Wienker, Peter A. Mossey, Peter Propping, Sven Cichon, Per Hoffmann, Michael Knapp, Markus M. Noethen, Elisabeth Mangold (Lead / Corresponding author)

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

375 Citations (Scopus)

Abstract

We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 x 10(-24). The odds ratio was 2.57 (95% CI = 2.02-3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88-9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.

Original language	English
Pages (from-to)	473-477
Number of pages	5
Journal	Nature Genetics
Volume	41
Issue number	4
DOIs	https://doi.org/10.1038/ng.333
Publication status	Published - Apr 2009

Keywords

GENOME-WIDE ASSOCIATION
GENETIC-VARIANTS
EXPRESSION
RISK
IRF6
METAANALYSIS
DISEASE
DESIGN
CANCER
SCAN

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.333

Cite this

Birnbaum, S., Ludwig, K. U., Reutter, H., Herms, S., Steffens, M., Rubini, M., Baluardo, C., Ferrian, M., de Assis, N. A., Alblas, M. A., Barth, S., Freudenberg, J., Lauster, C., Schmidt, G., Scheer, M., Braumann, B., Berge, S. J., Reich, R. H., Schiefke, F., ... Mangold, E. (2009). Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24. Nature Genetics, 41(4), 473-477. https://doi.org/10.1038/ng.333

@article{068123b0bf3a492ab3b0fde17b048565,

title = "Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24",

abstract = "We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 x 10(-24). The odds ratio was 2.57 (95% CI = 2.02-3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88-9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.",

keywords = "GENOME-WIDE ASSOCIATION, GENETIC-VARIANTS, EXPRESSION, RISK, IRF6, METAANALYSIS, DISEASE, DESIGN, CANCER, SCAN",

author = "Stefanie Birnbaum and Ludwig, {Kerstin U.} and Heiko Reutter and Stefan Herms and Michael Steffens and Michele Rubini and Carlotta Baluardo and Melissa Ferrian and {de Assis}, {Nilma Almeida} and Alblas, {Margrieta A.} and Sandra Barth and Jan Freudenberg and Carola Lauster and Guel Schmidt and Martin Scheer and Bert Braumann and Berge, {Stefaan J.} and Reich, {Rudolf H.} and Franziska Schiefke and Alexander Hemprich and Simone Poetzsch and Steegers-Theunissen, {Regine P.} and Bernd Poetzsch and Susanne Moebus and Bernhard Horsthemke and Franz-Josef Kramer and Wienker, {Thomas F.} and Mossey, {Peter A.} and Peter Propping and Sven Cichon and Per Hoffmann and Michael Knapp and Noethen, {Markus M.} and Elisabeth Mangold",

year = "2009",

month = apr,

doi = "10.1038/ng.333",

language = "English",

volume = "41",

pages = "473--477",

journal = "Nature Genetics",

issn = "1061-4036",

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Birnbaum, S, Ludwig, KU, Reutter, H, Herms, S, Steffens, M, Rubini, M, Baluardo, C, Ferrian, M, de Assis, NA, Alblas, MA, Barth, S, Freudenberg, J, Lauster, C, Schmidt, G, Scheer, M, Braumann, B, Berge, SJ, Reich, RH, Schiefke, F, Hemprich, A, Poetzsch, S, Steegers-Theunissen, RP, Poetzsch, B, Moebus, S, Horsthemke, B, Kramer, F-J, Wienker, TF, Mossey, PA, Propping, P, Cichon, S, Hoffmann, P, Knapp, M, Noethen, MM & Mangold, E 2009, 'Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24', Nature Genetics, vol. 41, no. 4, pp. 473-477. https://doi.org/10.1038/ng.333

TY - JOUR

T1 - Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24

AU - Birnbaum, Stefanie

AU - Ludwig, Kerstin U.

AU - Reutter, Heiko

AU - Herms, Stefan

AU - Steffens, Michael

AU - Rubini, Michele

AU - Baluardo, Carlotta

AU - Ferrian, Melissa

AU - de Assis, Nilma Almeida

AU - Alblas, Margrieta A.

AU - Barth, Sandra

AU - Freudenberg, Jan

AU - Lauster, Carola

AU - Schmidt, Guel

AU - Scheer, Martin

AU - Braumann, Bert

AU - Berge, Stefaan J.

AU - Reich, Rudolf H.

AU - Schiefke, Franziska

AU - Hemprich, Alexander

AU - Poetzsch, Simone

AU - Steegers-Theunissen, Regine P.

AU - Poetzsch, Bernd

AU - Moebus, Susanne

AU - Horsthemke, Bernhard

AU - Kramer, Franz-Josef

AU - Wienker, Thomas F.

AU - Mossey, Peter A.

AU - Propping, Peter

AU - Cichon, Sven

AU - Hoffmann, Per

AU - Knapp, Michael

AU - Noethen, Markus M.

AU - Mangold, Elisabeth

PY - 2009/4

Y1 - 2009/4

N2 - We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 x 10(-24). The odds ratio was 2.57 (95% CI = 2.02-3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88-9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.

AB - We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 x 10(-24). The odds ratio was 2.57 (95% CI = 2.02-3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88-9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.

KW - GENOME-WIDE ASSOCIATION

KW - GENETIC-VARIANTS

KW - EXPRESSION

KW - RISK

KW - IRF6

KW - METAANALYSIS

KW - DISEASE

KW - DESIGN

KW - CANCER

KW - SCAN

UR - http://www.scopus.com/inward/record.url?scp=63449105241&partnerID=8YFLogxK

U2 - 10.1038/ng.333

DO - 10.1038/ng.333

M3 - Article

SN - 1061-4036

VL - 41

SP - 473

EP - 477

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24

Abstract

Keywords

UN SDGs

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