Approach to the Immunosuppressed Patient with Pulmonary Infiltrates

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65614/1/j.1365-4362.1980.tb00811.x.pd

Summary statistics of consortium GWAS for dental caries in paediatric populations

Results of GWAS for caries in the primary dentition and permanent dentition. Genome-wide summary statistics are included for caries in the primary dentition ( European ancestry and multi-ethnic analyses) and caries in the permanent dentition (European ancestry only). In addition, results of follow up analyses and scripts to reproduce analyses are provided. See readme and pre-print article for further information

Low-frequency synonymous coding variation in CYP2R1 has large effects on Vitamin D levels and risk of multiple sclerosis

Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G > A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 x 10 -88). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.7-2.78, p = 1.26 x10 -12). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 x 10 -5) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis