Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects.

BACKGROUND: Neural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population. METHODS: Replication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case-control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case-control models and NTD groupings in white, African American and Hispanic cohorts from NYS. RESULTS: Of the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans. CONCLUSIONS: We report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis.

Author Correction: Growth and longevity in giant barrel sponges: Redwoods of the reef or Pines in the Indo-Pacific?

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Growth and longevity in giant barrel sponges: Redwoods of the reef or Pines in the Indo-Pacific?

Describing life history dynamics of functionally important species is critical for successful management. Barrel sponges (Xestospongia spp.) fill ecologically important roles on coral reefs due to their large size and water column interactions. Studies of Caribbean X. muta suggest they may be up to 1000 s of years old. However, nothing is known of barrel sponge growth rates outside the Caribbean. We assessed Indo-Pacific barrel sponge demography with a focus on specific growth rate (SGR), density, and mean volume across four sites of varying habitat quality. Four growth models were compared using Akaike's Information Criterion using a multi-model inference approach. Age was extrapolated and validated based on sponge size on a shipwreck of known age. Sponges from different sites showed differences in density, volume gained, and mean volume, but not growth rates. Interestingly, SGRs were slightly slower than that of X. muta, yet growth models supported rapid growth; Indo-Pacific sponges were over twice as old as published estimates of comparably sized X. muta (53-55 as compared to 23 years of age, respectively), although extrapolation errors are likely to increase with sponge size. This suggests that barrel sponge growth rates in the Indo-Pacific might be more comparable to Pines rather than Redwoods.

Newborn screening for congenital adrenal hyperplasia in New York State.

From 2007 to 2014 the New York State (NYS) Newborn Screening (NBS) program screened 2 million newborns for congenital adrenal hyperplasia (CAH). The data was analyzed to determine factors that affect 17α-hydroxyprogesterone levels and assist in developing algorithm changes that would improve the positive predictive value of the methodology being used. The concentration of 17-OHP in dried blood spots was measured using the AutoDELFIA Neonatal 17-OHP kit (Perkin Elmer, Turku, Finland). During the 8 year period of this study 2476 babies were referred, 105 babies were diagnosed with CAH (90 with the salt-wasting (SW), 8 with simple virilizing (SV), 5 with non-classical CAH, and 2 with another enzyme deficiency) and, 14 with possible CAH. Three false negative cases with SV-CAH were reported to the program. Of the total 108 known cases, 74 (69%) infants were detected by newborn screening in the absence of clinical information, or, known family history. The incidence of CAH in NYS is 1 in 18,170 with a ratio of SW to SV of 8.2:1. The incidence of CAH is lower in Black infants than in White, Hispanic and Asian infants. Despite a lower mean birth weight, female infants have a lower mean 17-OHP value than male infants and are under-represented in the referred category. As per other NBS programs the false positive rate is exacerbated by prematurity/low birth weight and by over-early specimen collection.