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For example, in orofacial clefting (OFC), three subtypes\u2014cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. To further dissect the genetic architecture of OFCs and how a given associated locus may be contributing to distinct subtypes of a trait we developed a framework for quantifying and interpreting evidence of subtype\u2010specific or shared genetic effects in complex traits. We applied this technique to create a \u201ccleft map\u201d of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype\u2010specific effects (e.g.,\n                    <jats:italic>GRHL3<\/jats:italic>\n                    [CP],\n                    <jats:italic>WNT5A<\/jats:italic>\n                    [CLP]), as well as loci associated with two or all three subtypes. We cross\u2010referenced these results with mouse craniofacial gene expression datasets, which identified additional promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed that neither subtype\u2010specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.\n                  <\/jats:p>","DOI":"10.1002\/gepi.22214","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T22:53:12Z","timestamp":1559861592000},"page":"704-716","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals"],"prefix":"10.1002","volume":"43","author":[{"given":"Jenna C.","family":"Carlson","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Graduate School of Public Health University of Pittsburgh Pittsburgh Pennsylvania"},{"name":"Department of Human Genetics, Graduate School of Public Health University of Pittsburgh Pittsburgh 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