The genetic architecture and evolution of the human skeletal form.

Autor: Kun E; Department of Integrative Biology, The University of Texas at Austin, Austin, TX, USA., Javan EM; Department of Integrative Biology, The University of Texas at Austin, Austin, TX, USA., Smith O; Department of Integrative Biology, The University of Texas at Austin, Austin, TX, USA., Gulamali F; Icahn School of Medicine at Mount Sinai, New York, NY, USA., de la Fuente J; Department of Psychology, The University of Texas at Austin, Austin, TX, USA., Flynn BI; Department of Integrative Biology, The University of Texas at Austin, Austin, TX, USA., Vajrala K; Department of Integrative Biology, The University of Texas at Austin, Austin, TX, USA., Trutner Z; Department of Surgery and Perioperative Care, The University of Texas at Austin, Austin, TX, USA., Jayakumar P; Department of Surgery and Perioperative Care, The University of Texas at Austin, Austin, TX, USA., Tucker-Drob EM; Department of Psychology, The University of Texas at Austin, Austin, TX, USA., Sohail M; Centro de Ciencias Genómicas (CCG), Universidad Nacional Autónoma de México (UNAM), 62209 Cuernavaca, Mexico., Singh T; Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA.; The New York Genome Center, New York, NY, USA.; Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia University, New York, NY, USA., Narasimhan VM; Department of Integrative Biology, The University of Texas at Austin, Austin, TX, USA.; Department of Statistics and Data Science, The University of Texas at Austin, Austin, TX, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2023 Jul 21; Vol. 381 (6655), pp. eadf8009. Date of Electronic Publication: 2023 Jul 21.
DOI: 10.1126/science.adf8009
Abstrakt: 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.
Databáze: MEDLINE
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