Is 7p14.1 an orofacial cleft risk locus? Genome-wide study of copy number variation in multiple populations provides both a replication of previous studies and an alternative explanation
The 7p14.1 association observed in our study is a replication of two prior studies in independent cohorts of European ancestry. However, this locus lies in a T-cell receptor region that is subject to somatic rearrangements that decrease in frequency with age and may affect genetic association results. Our data show age effects as well as differences between blood and saliva samples. Thus, our results can be interpreted either as supporting a previously established association with orofacial clefts, or as questioning those previous results in favor of a hypothesis about the behavior of somatic rearrangements in T-cell receptor regions.
Authors
- Fernando A. Poletta (ORCID: https://orcid.org/0000-0002-6102-8416)
- Alba Sanchis-Juan
- Myoung Keun Lee (ORCID: https://orcid.org/0000-0003-1508-9661)
- Jacqueline T. Hecht (ORCID: https://orcid.org/0000-0002-9087-3379)
- Seth M. Weinberg (ORCID: https://orcid.org/0000-0001-9467-4556)
- Eleanor Feingold (ORCID: https://orcid.org/0000-0003-2898-6484)
- Luz Consuelo Valencia‐Ramirez
- Claudia P. Restrepo Muñeton
- Nandita Mukhopadhyay (ORCID: https://orcid.org/0000-0001-7117-9536)
- Mekonen Eshete Abebe
- M. M. Marazita
- John R. Shaffer
- Iêda M. Orioli
- L. M. Moreno-Uribe
- George L. Wehby
- Elizabeth J Leslie-Clarkson
- Ingo Ruczinski
- Carmencita Padilla
- Wasiu L Adeyemo
- Carmen J Buxo
- Alexandre R Vieira
- Azeez Butali
- Edibe Nehir Kurtas
- Jeffrey C Murray
- Frederic Deleyiannis
Institutions
- Universidade Federal do Rio de Janeiro (BR)
- University of Iowa (US)
- Bloomberg (United States) (US)
- Oregon State University (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Emory University (US)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- University of Pittsburgh (US)
- East Carolina University (US)
- University of Lagos (NG)
- University of Puerto Rico System (PR)
- Universidad de Antioquia (CO)
- University of Colorado Health (US)
- Balaji Dental & Craniofacial Hospital (IN)
- International Craniofacial Institute (US)
- National Institute on Population Medical Genetics (BR)
- Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (AR)
- Center for Genomic Science (IT)
- Addis Ababa University (ET)
- University of the Philippines Manila (PH)
- The University of Texas Health Science Center at Houston (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-01-15
- DOI
- https://doi.org/10.64898/2026.01.09.26343782
- Primary Topic
- Cleft Lip and Palate Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Pittsburgh
- National Institutes of Health
- Center for Research Computing, University of Pittsburgh