Evidence map›Paper›PMID 36184229›Full record

ArticleClinical nutrition ESPEN2022

Genetic factors help explain the variable responses of young children with cystic fibrosis to vitamin D supplements.

HuiChuan J Lai, Jie Song, Qiongshi Lu, Sangita G Murali, Manavalan Gajapathy, Brandon M Wilk, Donna M Brown, Elizabeth A Worthey, Philip M Farrell, FIRST Study Group

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical nutrition ESPEN, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Vitamin D status and variable responses to supplements depend in part on genetic factors in adults with cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2024
    Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

HuiChuan J LaiDepartment of Nutritional Sciences, University of Wisconsin - Madison, WI, USA; Department of Pediatrics, University of Wisconsin - Madison, WI, USA; Department of Population Health Sciences, University of Wisconsin - Madison, WI, USA. Electronic address: hlai@wisc.edu.
Jie SongDepartment of Statistics, University of Wisconsin - Madison, WI, USA.
Qiongshi LuDepartment of Statistics, University of Wisconsin - Madison, WI, USA; Department of Biostatistics and Medical Informatics, University of Wisconsin - Madison, WI, USA.
Sangita G MuraliDepartment of Nutritional Sciences, University of Wisconsin - Madison, WI, USA.
Manavalan GajapathyDepartment of Pediatrics, Center for Computational Genomics and Data Science at the UAB Marnix E. Heersink School of Medicine, Birmingham, AL, USA.
Brandon M WilkDepartment of Pediatrics, Center for Computational Genomics and Data Science at the UAB Marnix E. Heersink School of Medicine, Birmingham, AL, USA.
Donna M BrownDepartment of Pediatrics, Center for Computational Genomics and Data Science at the UAB Marnix E. Heersink School of Medicine, Birmingham, AL, USA.
Elizabeth A WortheyDepartment of Pediatrics, Center for Computational Genomics and Data Science at the UAB Marnix E. Heersink School of Medicine, Birmingham, AL, USA.
Philip M FarrellDepartment of Pediatrics, University of Wisconsin - Madison, WI, USA; Department of Population Health Sciences, University of Wisconsin - Madison, WI, USA.
FIRST Study Group
University of Wisconsin–Madison · US

Funding

Newborn Screening, Malnutrition and Lung Disease in Children with Cystic FibrosisR01DK072126 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI LAI, HUICHUAN J · 2006 to 2015
$4.3M
Early Childhood Diet, Growth, Gut Microbiome And Lung Health in Cystic FibrosisR01DK109692 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI LAI, HUICHUAN J · 2016 to 2021
$3.8M
Early Childhood Diet, Growth, Gut Microbiome and Lung Health in Cystic FibrosisR56DK109692 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI LAI, HUICHUAN J · 2015 to 2015
$150k
NIDDK NIH HHS R01 DK072126NIDDK NIH HHS R01 DK109692NIDDK NIH HHS R56 DK109692
6 · The paper itself

Abstract

BACKGROUND &

aimsChildren with cystic fibrosis (CF) are susceptible to fat-soluble vitamin deficiencies unless supplemented, but even large doses of vitamin D may not prevent low 25-hydroxyvitamin D (25OHD) concentrations. The explanation for these vitamin D non-responders has been elusive. We utilized data from whole genome sequencing (WGS) to test the hypothesis that genetic variations predict responsiveness to vitamin D supplementation in a prospective cohort study of children with CF in the first 3 years of life.

methodsOne hundred and one infants born during 2012-2017 and diagnosed with CF through newborn screening were studied. Serum 25OHD concentrations and vitamin D supplement doses were assessed during early infancy and annually thereafter. WGS was performed, the resultant variant calling files processed, and the summary statistics from a recent genome-wide association study were utilized to construct a polygenic risk score (PRS) for each subject.

resultsOverall, the prevalence of vitamin D insufficiency (<30 ng/mL) was 21% in the first 3 years of life. Among the 70 subjects who always adhered to vitamin D supplement doses recommended by the US CF Foundation guidelines, 89% were responders (achieved vitamin D sufficiency) by 3 years of age, while 11% were transient or non-responders. Multiple regression analysis revealed that PRS was a significant predictor of 25OHD concentrations (p < 0.001) and the likelihood of being an earlier responder in the first 3 years of life (p < 0.01). A limited SNP analysis revealed variants in four important genes (GC, LIPC, CYP24A1, and PDE3B) that were shown to be associated with 25OHD concentrations and vitamin D responder status. Other determinants included vitamin D supplement dose, season at 25OHD measurement, and pancreatic functional status.

conclusionsApplying WGS in conjunction with utilizing a PRS approach revealed genetic variations that partially explain the unresponsiveness of some children with CF to vitamin D supplementation. Our findings suggest that a nutrigenomics strategy could help promote personalized treatment in CF.

Indexed as

Cystic FibrosisVitamin D DeficiencyChildChild, PreschoolDietary SupplementsGenome-Wide Association StudyHumansInfantInfant, NewbornProspective StudiesVitamin DVitamin D3 24-HydroxylaseVitaminsVitamin DVitamin D3 24-HydroxylaseVitamins25-Hydroxyvitamin DCystic fibrosisPolygenic risk scoreSingle nucleotide polymorphismVitamin D supplementationWhole genome sequencing

Identifiers

PMID36184229
PMCPMC11648032
OpenAlexW4293410733

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.