Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci

Kerstin U. Ludwig; Elisabeth Mangold; Stefan Herms; Stefanie Nowak; Heiko Reutter; Anna Paul; Jessica Becker; Ruth Herberz; Taofik Alchawa; Entessar Nasser; Anne C. Böhmer; Manuel Mattheisen; Margrieta A. Alblas; Sandra Barth; Nadine Kluck; Carola Lauster; Bert Braumann; Rudolf H. Reich; Alexander Hemprich; Simone Pötzsch; Bettina Blaumeiser; Nikolaos Daratsianos; Thomas Kreusch; Jeffrey C. Murray; Mary L. Marazita; Ingo Ruczinski; Alan F. Scott; Terri H. Beaty; Franz Josef Kramer; Thomas F. Wienker; Regine P. Steegers-Theunissen; Michele Rubini; Peter A. Mossey; Per Hoffmann; Christoph Lange; Sven Cichon; Peter Propping; Michael Knapp; Markus M. Nöthen

doi:10.1038/ng.2360

Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci

Kerstin U. Ludwig, Elisabeth Mangold, Stefan Herms, Stefanie Nowak, Heiko Reutter, Anna Paul, Jessica Becker, Ruth Herberz, Taofik Alchawa, Entessar Nasser, Anne C. Böhmer, Manuel Mattheisen, Margrieta A. Alblas, Sandra Barth, Nadine Kluck, Carola Lauster, Bert Braumann, Rudolf H. Reich, Alexander Hemprich, Simone PötzschBettina Blaumeiser, Nikolaos Daratsianos, Thomas Kreusch, Jeffrey C. Murray, Mary L. Marazita, Ingo Ruczinski, Alan F. Scott, Terri H. Beaty, Franz Josef Kramer, Thomas F. Wienker, Regine P. Steegers-Theunissen, Michele Rubini, Peter A. Mossey, Per Hoffmann, Christoph Lange, Sven Cichon, Peter Propping, Michael Knapp, Markus M. Nöthen

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Abstract

We have conducted the first meta-analyses for nonsyndromic cleft lip with or without cleft palate (NSCL/P) using data from the two largest genome-wide association studies published to date. We confirmed associations with all previously identified loci and identified six additional susceptibility regions (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic variability identified the first specific genetic risk factor for NSCLP (nonsyndromic cleft lip plus palate) (rs8001641; P_NSCLP = 6.51 × 10^-11; homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84-3.16).

Original language	English (US)
Pages (from-to)	968-971
Number of pages	4
Journal	Nature genetics
Volume	44
Issue number	9
DOIs	https://doi.org/10.1038/ng.2360
State	Published - Sep 2012

ASJC Scopus subject areas

Genetics

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Ludwig, K. U., Mangold, E., Herms, S., Nowak, S., Reutter, H., Paul, A., Becker, J., Herberz, R., Alchawa, T., Nasser, E., Böhmer, A. C., Mattheisen, M., Alblas, M. A., Barth, S., Kluck, N., Lauster, C., Braumann, B., Reich, R. H., Hemprich, A., ... Nöthen, M. M. (2012). Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. Nature genetics, 44(9), 968-971. https://doi.org/10.1038/ng.2360

Ludwig, KU, Mangold, E, Herms, S, Nowak, S, Reutter, H, Paul, A, Becker, J, Herberz, R, Alchawa, T, Nasser, E, Böhmer, AC, Mattheisen, M, Alblas, MA, Barth, S, Kluck, N, Lauster, C, Braumann, B, Reich, RH, Hemprich, A, Pötzsch, S, Blaumeiser, B, Daratsianos, N, Kreusch, T, Murray, JC, Marazita, ML, Ruczinski, I , Scott, AF , Beaty, TH, Kramer, FJ, Wienker, TF, Steegers-Theunissen, RP, Rubini, M, Mossey, PA, Hoffmann, P, Lange, C, Cichon, S, Propping, P, Knapp, M & Nöthen, MM 2012, 'Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci', Nature genetics, vol. 44, no. 9, pp. 968-971. https://doi.org/10.1038/ng.2360

@article{e81bc76343124f27b45beed9db86f4b1,

title = "Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci",

abstract = "We have conducted the first meta-analyses for nonsyndromic cleft lip with or without cleft palate (NSCL/P) using data from the two largest genome-wide association studies published to date. We confirmed associations with all previously identified loci and identified six additional susceptibility regions (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic variability identified the first specific genetic risk factor for NSCLP (nonsyndromic cleft lip plus palate) (rs8001641; PNSCLP = 6.51 × 10-11; homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84-3.16).",

author = "Ludwig, {Kerstin U.} and Elisabeth Mangold and Stefan Herms and Stefanie Nowak and Heiko Reutter and Anna Paul and Jessica Becker and Ruth Herberz and Taofik Alchawa and Entessar Nasser and B{\"o}hmer, {Anne C.} and Manuel Mattheisen and Alblas, {Margrieta A.} and Sandra Barth and Nadine Kluck and Carola Lauster and Bert Braumann and Reich, {Rudolf H.} and Alexander Hemprich and Simone P{\"o}tzsch and Bettina Blaumeiser and Nikolaos Daratsianos and Thomas Kreusch and Murray, {Jeffrey C.} and Marazita, {Mary L.} and Ingo Ruczinski and Scott, {Alan F.} and Beaty, {Terri H.} and Kramer, {Franz Josef} and Wienker, {Thomas F.} and Steegers-Theunissen, {Regine P.} and Michele Rubini and Mossey, {Peter A.} and Per Hoffmann and Christoph Lange and Sven Cichon and Peter Propping and Michael Knapp and N{\"o}then, {Markus M.}",

note = "Funding Information: We thank all affected individuals and their families for their participation in this study, as well as the German support group for people with cleft lip and/or palate (Deutsche Selbsthilfevereinigung f{\"u}r Lippen-Gaumen-Fehlbildungen e.V.). The study was supported by the Deutsche Forschungsgemeinschaft (FOR 423 and individual grants MA 2546/3-1, KR 1912/7-1, NO 246/6-1 and WI 1555/5-1) and the Austrian Cleft Palate Craniofacial Association (ACPCA). T.A. and E.N. are supported by grants from the Ministry of Higher Education, Syrian Arab Republic. The data sets used for the analyses described in this manuscript were obtained from dbGaP under accession phs000094.v1.p1. Additional acknowledgments are provided in the Supplementary Note.",

year = "2012",

month = sep,

doi = "10.1038/ng.2360",

language = "English (US)",

volume = "44",

pages = "968--971",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

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TY - JOUR

T1 - Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci

AU - Ludwig, Kerstin U.

AU - Mangold, Elisabeth

AU - Herms, Stefan

AU - Nowak, Stefanie

AU - Reutter, Heiko

AU - Paul, Anna

AU - Becker, Jessica

AU - Herberz, Ruth

AU - Alchawa, Taofik

AU - Nasser, Entessar

AU - Böhmer, Anne C.

AU - Mattheisen, Manuel

AU - Alblas, Margrieta A.

AU - Barth, Sandra

AU - Kluck, Nadine

AU - Lauster, Carola

AU - Braumann, Bert

AU - Reich, Rudolf H.

AU - Hemprich, Alexander

AU - Pötzsch, Simone

AU - Blaumeiser, Bettina

AU - Daratsianos, Nikolaos

AU - Kreusch, Thomas

AU - Murray, Jeffrey C.

AU - Marazita, Mary L.

AU - Ruczinski, Ingo

AU - Scott, Alan F.

AU - Beaty, Terri H.

AU - Kramer, Franz Josef

AU - Wienker, Thomas F.

AU - Steegers-Theunissen, Regine P.

AU - Rubini, Michele

AU - Mossey, Peter A.

AU - Hoffmann, Per

AU - Lange, Christoph

AU - Cichon, Sven

AU - Propping, Peter

AU - Knapp, Michael

AU - Nöthen, Markus M.

N1 - Funding Information: We thank all affected individuals and their families for their participation in this study, as well as the German support group for people with cleft lip and/or palate (Deutsche Selbsthilfevereinigung für Lippen-Gaumen-Fehlbildungen e.V.). The study was supported by the Deutsche Forschungsgemeinschaft (FOR 423 and individual grants MA 2546/3-1, KR 1912/7-1, NO 246/6-1 and WI 1555/5-1) and the Austrian Cleft Palate Craniofacial Association (ACPCA). T.A. and E.N. are supported by grants from the Ministry of Higher Education, Syrian Arab Republic. The data sets used for the analyses described in this manuscript were obtained from dbGaP under accession phs000094.v1.p1. Additional acknowledgments are provided in the Supplementary Note.

PY - 2012/9

Y1 - 2012/9

N2 - We have conducted the first meta-analyses for nonsyndromic cleft lip with or without cleft palate (NSCL/P) using data from the two largest genome-wide association studies published to date. We confirmed associations with all previously identified loci and identified six additional susceptibility regions (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic variability identified the first specific genetic risk factor for NSCLP (nonsyndromic cleft lip plus palate) (rs8001641; PNSCLP = 6.51 × 10-11; homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84-3.16).

AB - We have conducted the first meta-analyses for nonsyndromic cleft lip with or without cleft palate (NSCL/P) using data from the two largest genome-wide association studies published to date. We confirmed associations with all previously identified loci and identified six additional susceptibility regions (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic variability identified the first specific genetic risk factor for NSCLP (nonsyndromic cleft lip plus palate) (rs8001641; PNSCLP = 6.51 × 10-11; homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84-3.16).

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DO - 10.1038/ng.2360

M3 - Article

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AN - SCOPUS:84865685465

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JO - Nature genetics

JF - Nature genetics

IS - 9

ER -

Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci

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