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Journal article
A missense variant in SLC39A8 is associated with severe idiopathic scoliosis
Nature communications, v 9(1), pp 4171-7
09 Oct 2018
PMID: 30301978
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Genetic factors predictive of severe adolescent idiopathic scoliosis (AIS) are largely unknown. To identify genetic variation associated with severe AIS, we performed an exome-wide association study of 457 severe AIS cases and 987 controls. We find a missense SNP in SLC39A8 (p.Ala391Thr, rs13107325) associated with severe AIS (P = 1.60 × 10
, OR = 2.01, CI = 1.54-2.62). This pleiotropic SNP was previously associated with BMI, blood pressure, cholesterol, and blood manganese level. We replicate the association in a second cohort (841 cases and 1095 controls) resulting in a combined P = 7.02 × 10
, OR = 1.94, CI = 1.63-2.34. Clinically, the minor allele of rs13107325 is associated with greater spinal curvature, decreased height, increased BMI and lower plasma manganese in our AIS cohort. Functional studies demonstrate reduced manganese influx mediated by the SLC39A8 p.Ala391Thr variant and vertebral abnormalities, impaired growth, and decreased motor activity in slc39a8 mutant zebrafish. Our results suggest the possibility that scoliosis may be amenable to dietary intervention.
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Details
- Title
- A missense variant in SLC39A8 is associated with severe idiopathic scoliosis
- Creators
- Gabe Haller - Washington University in St. LouisKevin McCall - Washington University in St. LouisSupak Jenkitkasemwong - University of Florida HealthBrooke Sadler - Washington University in St. LouisLilian Antunes - Washington University in St. LouisMomchil Nikolov - Washington University in St. LouisJulia Whittle - Washington University in St. LouisZachary Upshaw - Washington University in St. LouisJimann Shin - Washington University in St. LouisErin Baschal - University of DenverCarlos Cruchaga - Washington University in St. LouisMatthew Harms - Columbia UniversityCathleen Raggio - Hospital for Special SurgeryJose A Morcuende - University of IowaPhilip Giampietro - Drexel UniversityNancy H Miller - University of DenverCarol Wise - Texas Scottish Rite Hospital for ChildrenRyan S Gray - The University of Texas at AustinLila Solnica-Krezel - Washington University in St. LouisMitchell Knutson - University of Florida HealthMatthew B Dobbs - Shriners Hospitals for ChildrenChristina A Gurnett - Washington University in St. Louis
- Publication Details
- Nature communications, v 9(1), pp 4171-7
- Publisher
- Springer Nature
- Grant note
- R01 AR067715 / NIAMS NIH HHS U54 HD087011 / NICHD NIH HHS T32 GM007067 / NIGMS NIH HHS R01 AR072009 / NIAMS NIH HHS P01 HD084387 / NICHD NIH HHS P01HD084387 / U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) UL1 TR002345 / NCATS NIH HHS R01AR067715 / U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) P30 HD062171 / NICHD NIH HHS R01 AR068292 / NIAMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000446800200009
- Scopus ID
- 2-s2.0-85054566394
- Other Identifier
- 991019167722004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity