Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Quality Evaluation of Maize Chips (Kokoro) Fortified with Cowpea Flour

Quality evaluation of “kokoro” fortified with cowpea flour (0, 10, 20, 30, and 40 %) was studied. The blends were reconstituted into a thick paste, manually moulded into kokoro stick and deep fried in hot vegetable oil at about 1700C for 5 minutes. These flour blends were analyzed for pasting, proximate and functional properties. The result showed that there was significant difference (p &lt; 0.05) in the proximate composition in all the bends. The protein content ranged from 15.20 – 23.03% while ash content was between 1.29 – 1.90%, which increased with increase in cowpea flour. The carbohydrate, fat and fiber contents decreased with values ranging from 59.17 – 65.00%, 3.24 – 4.40% and 2.23 – 2.96%, respectively. The pasting characteristics of the maize cowpea blends gave a peak viscosity ranging from 510 – 702 cp. There was no significant difference (p &gt; 0.05) in the pasting time and temperature. The functional properties reflected that water absorption, oil absorption and foaming capacity significantly increased with increase in cowpea flour with their values ranging from 186.67 – 210.00 g/100 g, 163.33 – 195.00 g/mg and 30.73 – 39.27% respectively. Bulk density also followed the same trend. Sample CAF (100% maize) reflected the highest dispersibility value (6.63%). No significant difference (p &gt; 0.05) was observed in the swelling capacity and least gelatinization concentration. Although the sensory result indicated that increase in cowpea flour does not show a significant difference (p &gt; 0.05) in the sensory parameters, the overall acceptability of the samples was highly rated.Keywords: Maize, cowpea, physicochemical properties, kokoro, fortification

NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality.

Disorders of water balance, an excess or deficit of total body water relative to body electrolyte content, are common and ascertained by plasma hypo- or hypernatremia, respectively. We performed a two-stage genome-wide association study meta-analysis on plasma sodium concentration in 45,889 individuals of European descent (stage 1 discovery) and 17,637 additional individuals of European descent (stage 2 replication), and a transethnic meta-analysis of replicated single-nucleotide polymorphisms in 79,506 individuals (63,526 individuals of European descent, 8765 individuals of Asian Indian descent, and 7215 individuals of African descent). In stage 1, we identified eight loci associated with plasma sodium concentration at P&lt;5.0 × 10(-6) Of these, rs9980 at NFAT5 replicated in stage 2 meta-analysis (P=3.1 × 10(-5)), with combined stages 1 and 2 genome-wide significance of P=5.6 × 10(-10) Transethnic meta-analysis further supported the association at rs9980 (P=5.9 × 10(-12)). Additionally, rs16846053 at SLC4A10 showed nominally, but not genome-wide, significant association in combined stages 1 and 2 meta-analysis (P=6.7 × 10(-8)). NFAT5 encodes a ubiquitously expressed transcription factor that coordinates the intracellular response to hypertonic stress but was not previously implicated in the regulation of systemic water balance. SLC4A10 encodes a sodium bicarbonate transporter with a brain-restricted expression pattern, and variant rs16846053 affects a putative intronic NFAT5 DNA binding motif. The lead variants for NFAT5 and SLC4A10 are cis expression quantitative trait loci in tissues of the central nervous system and relevant to transcriptional regulation. Thus, genetic variation in NFAT5 and SLC4A10 expression and function in the central nervous system may affect the regulation of systemic water balance

A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension

10.1371/journal.pgen.1005035PLoS Genetics113e100503

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press