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., inter-landm...

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Main Authors: Meng Yuan, Seppe Goovaerts, Michiel Vanneste, Harold Matthews, Hanne Hoskens, Stephen Richmond, Ophir D Klein, Richard A Spritz, Benedikt Hallgrimsson, Susan Walsh, Mark D Shriver, John R Shaffer, Seth M Weinberg, Hilde Peeters, Peter Claes
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-12-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1012617
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author Meng Yuan
Seppe Goovaerts
Michiel Vanneste
Harold Matthews
Hanne Hoskens
Stephen Richmond
Ophir D Klein
Richard A Spritz
Benedikt Hallgrimsson
Susan Walsh
Mark D Shriver
John R Shaffer
Seth M Weinberg
Hilde Peeters
Peter Claes
author_facet Meng Yuan
Seppe Goovaerts
Michiel Vanneste
Harold Matthews
Hanne Hoskens
Stephen Richmond
Ophir D Klein
Richard A Spritz
Benedikt Hallgrimsson
Susan Walsh
Mark D Shriver
John R Shaffer
Seth M Weinberg
Hilde Peeters
Peter Claes
author_sort Meng Yuan
collection DOAJ
description 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., inter-landmark distances), unsupervised dimensionality reductions (e.g., principal component analysis (PCA) and auto-encoder (AE) approaches), and assessing resemblance to particular facial gestalts (e.g., syndromic facial archetypes). This study provides a comparative assessment of these strategies in genome-wide association studies (GWASs) of 3D facial shape. Specifically, we investigated inter-landmark distances, PCA and AE-derived latent dimensions, and facial resemblance to random, extreme, and syndromic gestalts within a GWAS of 8,426 individuals of recent European ancestry. Inter-landmark distances exhibit the highest SNP-based heritability as estimated via LD score regression, followed by AE dimensions. Conversely, resemblance scores to extreme and syndromic facial gestalts display the lowest heritability, in line with expectations. Notably, the aggregation of multiple GWASs on facial resemblance to random gestalts reveals the highest number of independent genetic loci. This novel, easy-to-implement phenotyping approach holds significant promise for capturing genetically relevant morphological traits derived from complex biomedical imaging datasets, and its applications extend beyond faces. Nevertheless, these different phenotyping strategies capture different genetic influences on craniofacial shape. Thus, it remains valuable to explore these strategies individually and in combination to gain a more comprehensive understanding of the genetic factors underlying craniofacial shape and related traits.
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spelling doaj-art-6b26a37bab2c41cfa4c709c15ce8a4482025-08-20T02:45:06ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582024-12-012012e101261710.1371/journal.pcbi.1012617Mapping genes for human face shape: Exploration of univariate phenotyping strategies.Meng YuanSeppe GoovaertsMichiel VannesteHarold MatthewsHanne HoskensStephen RichmondOphir D KleinRichard A SpritzBenedikt HallgrimssonSusan WalshMark D ShriverJohn R ShafferSeth M WeinbergHilde PeetersPeter ClaesHuman 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., inter-landmark distances), unsupervised dimensionality reductions (e.g., principal component analysis (PCA) and auto-encoder (AE) approaches), and assessing resemblance to particular facial gestalts (e.g., syndromic facial archetypes). This study provides a comparative assessment of these strategies in genome-wide association studies (GWASs) of 3D facial shape. Specifically, we investigated inter-landmark distances, PCA and AE-derived latent dimensions, and facial resemblance to random, extreme, and syndromic gestalts within a GWAS of 8,426 individuals of recent European ancestry. Inter-landmark distances exhibit the highest SNP-based heritability as estimated via LD score regression, followed by AE dimensions. Conversely, resemblance scores to extreme and syndromic facial gestalts display the lowest heritability, in line with expectations. Notably, the aggregation of multiple GWASs on facial resemblance to random gestalts reveals the highest number of independent genetic loci. This novel, easy-to-implement phenotyping approach holds significant promise for capturing genetically relevant morphological traits derived from complex biomedical imaging datasets, and its applications extend beyond faces. Nevertheless, these different phenotyping strategies capture different genetic influences on craniofacial shape. Thus, it remains valuable to explore these strategies individually and in combination to gain a more comprehensive understanding of the genetic factors underlying craniofacial shape and related traits.https://doi.org/10.1371/journal.pcbi.1012617
spellingShingle Meng Yuan
Seppe Goovaerts
Michiel Vanneste
Harold Matthews
Hanne Hoskens
Stephen Richmond
Ophir D Klein
Richard A Spritz
Benedikt Hallgrimsson
Susan Walsh
Mark D Shriver
John R Shaffer
Seth M Weinberg
Hilde Peeters
Peter Claes
Mapping genes for human face shape: Exploration of univariate phenotyping strategies.
PLoS Computational Biology
title Mapping genes for human face shape: Exploration of univariate phenotyping strategies.
title_full Mapping genes for human face shape: Exploration of univariate phenotyping strategies.
title_fullStr Mapping genes for human face shape: Exploration of univariate phenotyping strategies.
title_full_unstemmed Mapping genes for human face shape: Exploration of univariate phenotyping strategies.
title_short Mapping genes for human face shape: Exploration of univariate phenotyping strategies.
title_sort mapping genes for human face shape exploration of univariate phenotyping strategies
url https://doi.org/10.1371/journal.pcbi.1012617
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