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

S Birnbaum; KU Ludwig; H Reutter; S Herms; M Steffens; M Rubini; C Baluardo; M Ferrian; NA de Assis; MA Alblas; S Barth; J Freudenberg; C Lauster; G Schmidt; M Scheer; B Braumann; SJ Berge; RH Reich; F Schiefke; A Hemprich; S Potzsch; Régine Steegers - Theunissen; B Potzsch; S Moebus; B Horsthemke; FJ Kramer; TF Wienker; PA Mossey; P Propping; S Cichon; P Hoffmann; M Knapp; MM Nothen; E Mangold

doi:10.1038/ng.333

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

S Birnbaum
, KU Ludwig
, H Reutter
, S Herms
, M Steffens
, M Rubini
, C Baluardo
, M Ferrian
, NA de Assis
, MA Alblas
, S Barth
, J Freudenberg
, C Lauster
, G Schmidt
, M Scheer
, B Braumann
, SJ Berge
, RH Reich
, F Schiefke
, A Hemprich

S Potzsch, Régine Steegers - Theunissen, B Potzsch, S Moebus, B Horsthemke, FJ Kramer, TF Wienker, PA Mossey, P Propping, S Cichon, P Hoffmann, M Knapp, MM Nothen, E Mangold

Obstetrics & Gynecology

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

391 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	Undefined/Unknown
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 - 2009

Research programs

EMC MGC-02-52-01-A
EMC MGC-02-96-01
EMC NIHES-01-64-02

Access to Document

10.1038/ng.333

http://hdl.handle.net/1765/15338

Cite this

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., ... 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

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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.",

author = "S Birnbaum and KU Ludwig and H Reutter and S Herms and M Steffens and M Rubini and C Baluardo and M Ferrian and \{de Assis\}, NA and MA Alblas and S Barth and J Freudenberg and C Lauster and G Schmidt and M Scheer and B Braumann and SJ Berge and RH Reich and F Schiefke and A Hemprich and S Potzsch and \{Steegers - Theunissen\}, R{\'e}gine and B Potzsch and S Moebus and B Horsthemke and FJ Kramer and TF Wienker and PA Mossey and P Propping and S Cichon and P Hoffmann and M Knapp and MM Nothen and E Mangold",

year = "2009",

doi = "10.1038/ng.333",

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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, Potzsch, S, Steegers - Theunissen, R, Potzsch, B, Moebus, S, Horsthemke, B, Kramer, FJ, Wienker, TF, Mossey, PA, Propping, P, Cichon, S, Hoffmann, P, Knapp, M, Nothen, 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, S

AU - Ludwig, KU

AU - Reutter, H

AU - Herms, S

AU - Steffens, M

AU - Rubini, M

AU - Baluardo, C

AU - Ferrian, M

AU - de Assis, NA

AU - Alblas, MA

AU - Barth, S

AU - Freudenberg, J

AU - Lauster, C

AU - Schmidt, G

AU - Scheer, M

AU - Braumann, B

AU - Berge, SJ

AU - Reich, RH

AU - Schiefke, F

AU - Hemprich, A

AU - Potzsch, S

AU - Steegers - Theunissen, Régine

AU - Potzsch, B

AU - Moebus, S

AU - Horsthemke, B

AU - Kramer, FJ

AU - Wienker, TF

AU - Mossey, PA

AU - Propping, P

AU - Cichon, S

AU - Hoffmann, P

AU - Knapp, M

AU - Nothen, MM

AU - Mangold, E

PY - 2009

Y1 - 2009

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.

U2 - 10.1038/ng.333

DO - 10.1038/ng.333

M3 - Article

C2 - 19270707

SN - 1061-4036

VL - 41

SP - 473

EP - 477

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -