Syndrome-informed phenotyping identifies a polygenic background for achondroplasia-like facial variation in the general population.

Human craniofacial shape is highly variable yet highly heritable with numerous genetic variants interacting through multiple layers of development. Here, we hypothesize that Mendelian phenotypes represent the extremes of a phenotypic spectrum and, using achondroplasia as an example, we introduce a syndrome-informed phenotyping approach to identify genomic loci associated with achondroplasia-like facial variation in the general population. We compare three-dimensional facial scans from 43 individuals with achondroplasia and 8246 controls to calculate achondroplasia-like facial scores.

Mapping genes for human face shape: Exploration of univariate phenotyping strategies.

Human facial shape, while strongly heritable, involves both genetic and structural complexity, necessitating precise phenotyping for accurate assessment. Common phenotyping strategies include simplifying 3D facial features into univariate traits such as anthropometric measurements (e.g.

Polygenic risk scores in the clinic: a systematic review of stakeholders' perspectives, attitudes, and experiences.

Polygenic Risk Scores (PRS) are statistical methods estimating part of an individual's genetic susceptibility to various disease phenotypes. Their potential clinical applications to enhance the prediction, prevention, and risk management of complex conditions motivate current research efforts worldwide. While a growing body of literature has highlighted the scientific and ethical limitations of PRS, the technology's clinical translation will present both opportunities and challenges for the stakeholders involved.

Multiple paralogues and recombination mechanisms contribute to the high incidence of 22q11.2 Deletion Syndrome.

The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder.