Genetic Variants Associated With the Biochemical Response to Vitamin D3 in the Multi-Ethnic Study of Atherosclerosis

Best, CM; Li, X; Rotter, JI; Prince, DK; Hsu, S; Hoofnagle, AN; Siscovick, D; Taylor, KD; Williams, K; Michos, ED; Psaty, BM; Shea, S; Rice, KM; Watson, KE; Allen, NB; Tracy, RP; Robinson-Cohen, C; de Boer, IH; Kestenbaum, BR

doi:10.1210/clinem/dgaf025

Osteoporosis, bone & mineral

Genetic Variants Associated With the Biochemical Response to Vitamin D3 in the Multi-Ethnic Study of Atherosclerosis

J Clin Endocrinol MetabPublished 16 Jan 2025Genetic association analysis within a randomised placebo-controlled trial

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Authors' conclusion

Our results reveal potential new pathways of vitamin D regulation that require replication in other vitamin D trials.

Study context

Population: Participants of the Multi-Ethnic Study of Atherosclerosis assigned to vitamin D3; mean age 73 years, 54% females; 36% White, 33% Black, 18% Hispanic, 14% Chinesevitamin D3 analytic sample
Participants: 427 participants

Comparison: Genetic variants vs biochemical response to vitamin D3 2000 IU daily
Vitamin D3n = 427
Primary endpoint: Changes in serum 1,25(OH)2D3, PTH and 25(OH)D3
Follow-up: 16 weeks

Methodological detailsnested in community-based cohort, genome-wide and candidate analyses, transethnic meta-analysis, Conducted between 2017 and 2019

Nested in community-based cohort
Genome-wide and candidate analyses
Transethnic meta-analysis
Conducted between 2017 and 2019

Primary result

As reported in the abstract

Genome-wide associations with biochemical response

Genome regions with significant SNP association (P < 5E-08) with 1 of the traits: 8
Regions associated with change in 1,25(OH)2D3: 2
Regions associated with change in PTH: 1
Regions associated with change in 25(OH)D3: 5
rs16867276 (intergenic, 2q31): change in serum 1,25(OH)2D3 per effect allele; only locus genome-wide significant in transethnic meta-analysis: +8.37 pg/mL; P = 4.93E-08
rs114044709 (adjacent to FAM20A): change in PTH per effect allele among Black participants: +20.32 pg/mL; P = 1.34E-08

Further findings

Candidate gene analyses

SNPs within SULT2A1 and CYP24A1 significantly associated with changes in 1,25(OH)2D3 and PTH, respectively: P < 0.05÷36 = .0014

Original publication

Genetic Variants Associated With the Biochemical Response to Vitamin D3 in the Multi-Ethnic Study of Atherosclerosis. J Clin Endocrinol Metab. Published 16 January 2025. doi:10.1210/clinem/dgaf025

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