The genetic architecture and evolution of the human skeletal form-Reference-Cited by-同舟云学术

The genetic architecture and evolution of the human skeletal form

Published:2023-07-21 Issue:6655 Volume:381 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Kun Eucharist¹^ORCID,Javan Emily M.¹^ORCID,Smith Olivia¹^ORCID,Gulamali Faris²^ORCID,de la Fuente Javier³^ORCID,Flynn Brianna I.¹^ORCID,Vajrala Kushal¹^ORCID,Trutner Zoe⁴^ORCID,Jayakumar Prakash⁴^ORCID,Tucker-Drob Elliot M.³^ORCID,Sohail Mashaal⁵^ORCID,Singh Tarjinder⁶⁷⁸^ORCID,Narasimhan Vagheesh M.¹⁹^ORCID

Affiliation:

1. Department of Integrative Biology, The University of Texas at Austin, Austin, TX, USA.

2. Icahn School of Medicine at Mount Sinai, New York, NY, USA.

3. Department of Psychology, The University of Texas at Austin, Austin, TX, USA.

4. Department of Surgery and Perioperative Care, The University of Texas at Austin, Austin, TX, USA.

5. Centro de Ciencias Genómicas (CCG), Universidad Nacional Autónoma de México (UNAM), 62209 Cuernavaca, Mexico.

6. Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA.

7. The New York Genome Center, New York, NY, USA.

8. Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia University, New York, NY, USA.

9. Department of Statistics and Data Science, The University of Texas at Austin, Austin, TX, USA.

Abstract

The human skeletal form underlies bipedalism, but the genetic basis of skeletal proportions (SPs) is not well characterized. We applied deep-learning models to 31,221 x-rays from the UK Biobank to extract a comprehensive set of SPs, which were associated with 145 independent loci genome-wide. Structural equation modeling suggested that limb proportions exhibited strong genetic sharing but were independent of width and torso proportions. Polygenic score analysis identified specific associations between osteoarthritis and hip and knee SPs. In contrast to other traits, SP loci were enriched in human accelerated regions and in regulatory elements of genes that are differentially expressed between humans and great apes. Combined, our work identifies specific genetic variants that affect the skeletal form and ties a major evolutionary facet of human anatomical change to pathogenesis.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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