Most methods to adjust BMC/BMD Z-scores for height were biased by age and/or HAZ. Adjustments using HAZ were least biased relative to HAZ and age and can be used to evaluate the effect of short or tall stature on BMC/BMD Z-scores.
A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
The gut of healthy human neonates is usually devoid of viruses at birth, but quickly becomes colonized, in some cases leading to gastrointestinal disorders 1 – 4 . Here we report that viral community assembly in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from infant meconium/early stool samples show few or no particles, but by one month of life particle numbers achieve 10 9 per gram, and these numbers appear to persist through life 5 – 7 . We investigated the origin of these viral populations using shotgun metagenomic sequencing of viral-enriched preparations and whole microbial communities, and followed up with targeted microbiological analyses. Results indicate that, early after birth, pioneer bacteria colonize the infant gut, and by one month prophage induced from these bacteria provide the predominant population of virus-like particles. By four months of life, identifiable viruses that replicate in human cells become more prominent. Multiple human viruses were more abundant in stool samples from babies exclusively fed formula versus those fed partially or fully on breast milk, paralleling reports that breast milk can be protective against viral infections 8 – 10 . Phage populations also differed associated with breastfeeding. Evidently colonization of the infant gut is stepwise, first mainly by temperate bacteriophages induced from pioneer bacteria, and later by viruses that replicate in human cells, with the second phase modulated by breastfeeding.
Diabetes mellitus has emerged as a common comorbidity in cystic fibrosis and is considered a clinical entity (cystic fibrosis-related diabetes, CFRD) distinct from that of type 1 diabetes (T1DM) and type 2 diabetes (T2DM). The relevance of this diagnosis extends not only from its imposition of additional medical burden but its association with worse health outcomes in individuals with CF. This paper will review the 2010 U.S. and other international guidelines for screening and treating CFRD. It will highlight newer data regarding early glucose and insulin secretion defects, mechanisms linking CFRD to worse outcomes, and recent advances in T2DM that may provide insights for CFRD; insulin secretion will be reviewed as background for these recent developments.
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