Skeletal age GWAS 2021

GWAS meta-analysis performed in two multiethnic cohorts of school-aged children: The Generation R Study and Bone Mineral Density in Childhood Study 2021

Meta-analysis included multiethnic children from the Generation R Study (GenR: N=3,510; multiethnic birth cohort in Rotterdam, NL) and the multi-centric Bone Mineral Density in Childhood Study (BMDCS: N=1,047; US). Skeletal age was assessed on X-ray (BMDCS) or DXA (GenR) images of the hand using the Greulich and Pyle method. Participants were genotyped with Illumina HumanHap 610 or 660 Quad chips (Illumina Inc., San Diego, USA) (GenR) and Illumina Infinium II OMNI Express plus Exome BeadChip technology (Illumina, San Diego, CA, USA) (BMDCS). Imputation to the 1000G Phase 3 (version 5) reference panel was carried out in the Michigan Imputation Server using the EAGLE2/minimac3 software (GenR) or using IMPUTE2 software (BMDCS). In subsequent analyses, only SNPs with MAF greater than 1% and sufficient imputation quality (r2=0.30) were analysed.

Standardized residuals of SA corrected for age and BMI and 10 genomic principal components (GenR) or visit site and initial/ancillary cohort status (BMDCS) were computed separately for boys and girls and used as outcomes. Association between genotypes (9,806,907 SNPs) and SA residuals was tested in the linear regression model (GenR) or linear mixed models (BMDCS). Fixed-effects inverse variance meta-analysis using METAL was performed and significance set at P<5x10-8.

GWAS data file description

Summary statistics are prepared for the total population and separately per gender. All files contain:

Presented as chromosome:position Effect allele, refers to effect size/beta Effect size Standard error of the effect size P-value

RNA-Seq data file descrition

Aligned .bam and .bai files are provided per sample. Chromosomal region 1MBp in size, stretching from 143,000,000 to 144,000,000 of the 8th chromosome, thus covering the CYP11B1 gene, has been extracted and is thus provided.

Phenotype data for samples can be additionally provided per e-mail inquiry. Please contact the corresponding author of the publication.


Grgic O, Gazzara MR, Chesi A, Medina-Gomez C, Cousminer DL, Mitchell JA, Prijatelj V, de Vries J, Shevroja E, McCormack SE, Kalkwarf HJ, Lappe JM, Gilsanz V, Oberfield SE, Shepherd JA, Kelly A, Mahboubi S, Faucz FR, Feelders RA, de Jong FH, Uitterlinden AG, Visser JA, Ghanem LR, Wolvius EB, Hofland LJ, Stratakis CA, Zemel BS, Barash Y, Grant SFA, Rivadeneira F. CYP11B1 variants influence skeletal maturation via alternative splicing. Commun Biol. 2021 Nov 9;4(1):1274. doi: 10.1038/s42003-021-02774-y. PMID: 34754074; PMCID: PMC8578655.