Common variants in DLG1 locus are associated with non‐syndromic cleft lip with or without cleft palate

Common variants in DLG1 locus are associated with non‐syndromic cleft lip with or without cleft... Non‐syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top‐associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft‐susceptibility locus in our genome‐wide association study (GWAS). Mega‐analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome‐wide level (Ptrend = 9.70E−10 and Ptrend = 8.96E−09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome‐wide significance threshold (Ptrend < 1.00E−05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft‐susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Genetics Wiley

Loading next page...
 
/lp/wiley/common-variants-in-dlg1-locus-are-associated-with-non-syndromic-cleft-W2AoJo06Ih
Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
ISSN
0009-9163
eISSN
1399-0004
D.O.I.
10.1111/cge.13141
Publisher site
See Article on Publisher Site

Abstract

Non‐syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top‐associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft‐susceptibility locus in our genome‐wide association study (GWAS). Mega‐analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome‐wide level (Ptrend = 9.70E−10 and Ptrend = 8.96E−09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome‐wide significance threshold (Ptrend < 1.00E−05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft‐susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly.

Journal

Clinical GeneticsWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial