Biology subjects

Wu, Y.

Publications and source records attributed to Wu, Y..

At least 1,045 records · Page 58Linked to original sources

bioRxiv2019

The genomic sequence and comparative genomic analysis of cultivated passion fruit(Passiflora edulis L.)

Cultivated passion fruit is a fruit tree widely cultivated in southern China, but little is known about its genomics, which seriously restricts the molecular genetics research of passion fruit. In this study, we analyzed the 165.7Mb representative genome sequences. The results showed that the passion fruit genome contained a large number of simple sequence repeats (SSR). Compared to the cassava and peach genomes, the passion fruit genome has 23,053 predicted genes. These genes can be aligned to 282 plant genomes. GO annotation indicated that these genes are involved in metabolic pathways of carbohydrates, organic acids, lipids and other molecules. KEGG pathway enrichment assigned these genes into five major categories and 19 secondary functions. Cluster analysis of gene families showed that 12,767 genes could be clustered into 9,868 gene families and 291 unique gene families. On the evolutionary relationship, the passion fruit is closely related to Populus trichocarpa and Ricinus communis, but the rate of evolution is slower. In summary, this genomic analysis result is informative, and will facilitate the future studies on gene functions of passion fruit.

genomics↗

bioRxiv2019

Genotype-by-environment interactions inferred from genetic effects on phenotypic variability in the UK Biobank

Genotype-by-environment interaction (GEI) is a fundamental component in understanding complex trait variation. However, it remains challenging to identify genetic variants with GEI effects in humans largely because of the small effect sizes and the difficulty of monitoring environmental fluctuations. Here, we demonstrate that GEI can be inferred from genetic variants associated with phenotypic variability in a large sample without the need of measuring environmental factors. We performed a genome-wide variance quantitative trait locus (vQTL) analysis of ~5.6 million variants on 348,501 unrelated individuals of European ancestry for 13 quantitative traits in the UK Biobank, and identified 75 significant vQTLs with P<2.0x10-9 for 9 traits, especially for those related to obesity. Direct GEI analysis with five environmental factors showed that the vQTLs were strongly enriched with GEI effects. Our results indicate pervasive GEI effects for obesity-related traits and demonstrate the detection of GEI without environmental data.

genetics↗

bioRxiv2019

Detecting Circular RNA from High-throughput Sequence Data with de Bruijn Graph

Circular RNA is a type of non-coding RNA, which has a circular structure. Many circular RNAs are stable and contain exons, but are not translated into proteins. Circular RNA has important functions in gene regulation and plays an important role in some human diseases. Several biological methods, such as RNase R treatment, have been developed to identify circular RNA. Multiple bioinformatics tools have also been developed for circular RNA detection with high-throughput sequence data. In this paper, we present circDBG, a new method for circular RNA detection with de Bruijn graph. We conduct various experiments to evaluate the performance of CircDBG based on both simulated and real data. Our results show that CircDBG finds more reliable cir-cRNAs with low bias, has more efficiency in running time, and performs better in balancing accuracy and sensitivity than existing methods. As a byproduct, we also introduce a new method to classify circular RNAs based on reads alignment. Finally, we report a potential chimeric circular RNA that is found by CircDBG based on real sequence data. CircDBG can be downloaded from https://github.com/lxwgcool/CircDBG.

bioinformatics↗

bioRxiv2018

The allotetraploid origin and asymmetrical genome evolution of common carp Cyprinus carpio

Common carp (Cyprinus carpio) is an allotetraploid Cyprinid species derived from recent whole genome duplication and provides an excellent model system for studying polyploid genome evolution in vertebrates. To explore the origins and consequences of tetraploidy in C. carpio, we generated three chromosome-level new reference genomes of C. carpio and compared them to the related diploid Cyprinid genome sequences. We identified a progenitor-like diploid Barbinae lineage by analysing the phylogenetic relationship of the homoeologous genes of C. carpio and their orthologues in closely related diploid Cyprinids. We then characterized the allotetraploid origin of C. carpio and divided its genome into two homoeologous subgenomes that are marked by a distinct genome similarity to their diploid progenitor. On the basis of the divergence rates of homoeologous genes and transposable elements in two subgenomes, we estimated that the two diploid progenitor species diverged approximately 23 million years ago (Mya) and merged to form the allotetraploid C. carpio approximately 12.4 Mya, which likely correlated with environmental upheavals caused by the extensive uplift of the Qinghai-Tibetan Plateau. No large-scale gene losses or rediploidization were observed in the two subgenomes. Instead, we found extensive homoeologous gene expression bias across twelve surveyed tissues, which indicates that subgenome B is dominant in homoeologous expression. DNA methylation analysis suggested that CG methylation in promoter regions plays an important role in altering the expression of these homoeologous genes in allotetraploid C. carpio. This study provides an essential genome resource and insights for extending further investigation on the evolutionary consequences of vertebrate polyploidy.

genomics↗

bioRxiv2018

Genetic analyses of medication-use and implications for precision medicine

It is common that one medication is prescribed for several indications, and conversely that several medications are prescribed for the same indication, suggesting a complex biological network for disease risk and its relationship with pharmacological function. Genome-wide association studies (GWASs) of medication-use may contribute to understanding of disease etiology, generation of new leads relevant for drug discovery and quantify prospects for precision medicine. We conducted GWAS to profile self-reported medication-use from 23 categories in approximately 320,000 individuals from the UK Biobank. A total of 505 independent genetic loci that met stringent criteria for statistical significance were identified. We investigated the implications of these GWAS findings in relation to biological mechanism, drug target identification and genetic risk stratification of disease. Amongst the medication-associated genes were 16 known therapeutic-effect target genes for medications from 9 categories.

genetics↗

bioRxiv2018

Continuous in vivo metabolism by NMR

Dense time-series metabolomics data are essential for unraveling the underlying dynamic properties of metabolism. Here we extend high-resolution-magic angle spinning (HR-MAS) to enable continuous in vivo monitoring of metabolism by NMR (CIVM-NMR) and provide analysis tools for these data. First, we reproduced a result in human chronic lymphoid leukemia cells by using isotope-edited CIVM-NMR to rapidly and unambiguously demonstrate unidirectional flux in branched-chain amino acid metabolism. We then collected untargeted CIVM-NMR datasets for Neurospora crassa, a classic multicellular model organism, and uncovered dynamics between central carbon metabolism, amino acid metabolism, energy storage molecules, and lipid and cell wall precursors. Virtually no sample preparation was required to yield a dynamic metabolic fingerprint over hours to days at ~4-min temporal resolution with little noise. CIVM-NMR is simple and readily adapted to different types of cells and microorganisms, offering an experimental complement to kinetic models of metabolism for diverse biological systems.

systems biology↗

bioRxiv2018

Co-Expression Network-based Analysis associated with potato initial resistance

RNA sequencing (RNA-seq) providing genome-wide expression datasets has been successfully used to study gene expression patterns and regulation mechanism among multiple samples. Gene co-expression networks (GCNs) studies within or across species showed that coordinated genes in expression patterns are often functionally related. For potatoes, a large amount of publicly available transcriptome datasets have been generated but an optimal GCN detecting expression patterns in different genotypes, tissues and environmental conditions, is lacking. We constructed a potato GCN using 16 published RNA-Seq datasets covering 11 cultivars from native habitat worldwide. The correlations of gene expression were assessed pair-wisely and biologically meaningful gene modules which are highly connected in GCN were identified. One of the primitively native-farmer-selected cultivars in the Andes, ssp.Andigena, had relative far distance in gene expression patterns with other modern varieties. GCN in further enriched 134 highly and specifically co-expressed genes in ssp.Andigena associated with potato disease and stress resistance, which underlying the dramatic shift in evolutionary pressures during potato artificial domestication. In total, the network was consisted of into 14 gene models that involves in a variety of plant processes, which sheds light on how gene modules organized intra- and inter-varieties in the context of evolutionary divergence and provides a basis of information resource for potato gene functional studies.

plant biology↗

bioRxiv2018

Tractography Reproducibility Challenge with Empirical Data (TraCED): The 2017 ISMRM Diffusion Study Group Challenge

PurposeFiber tracking with diffusion weighted magnetic resonance imaging has become an essential tool for estimating in vivo brain white matter architecture. Fiber tracking results are sensitive to the choice of processing method and tracking criteria. Phantom studies provide concrete quantitative comparisons of methods relative to absolute ground truths, yet do not capture variabilities because of in vivo physiological factors.\n\nMethodsTo date, a large-scale reproducibility analysis has not been performed for the assessment of the newest generation of tractography algorithms with in vivo data. Reproducibility does not assess the validity of a brain connection however it is still of critical importance because it describes the variability for an algorithm in group studies. The ISMRM 2017 TraCED challenge was created to fulfill the gap. The TraCED dataset consists of a single healthy volunteer scanned on two different scanners of the same manufacturer. The multi-shell acquisition included b-values of 1000, 2000 and 3000 s/mm2 with 20, 45 and 64 diffusion gradient directions per shell, respectively.\n\nResultsNine international groups submitted 46 tractography algorithm entries. The top five submissions had high ICC > 0.88. Reproducibility is high within these top 5 submissions when assessed across sessions or across scanners. However, it can be directly attributed to containment of smaller volume tracts in larger volume tracts. This holds true for the top five submissions where they are contained in a specific order. While most algorithms are contained in an ordering there are some outliers.\n\nConclusionThe different methods clearly result in fundamentally different tract structures at the more conservative specificity choices (i.e., volumetrically smaller tractograms). The data and challenge infrastructure remain available for continued analysis and provide a platform for comparison.

neuroscience↗

bioRxiv2018

Structural and biochemical studies define Nudt12 as a new class of RNA deNADding enzyme in mammalian cells

We recently demonstrated mammalian cells harbor NAD-capped mRNAs that are hydrolyzed by the DXO deNADding enzyme. Here we report the Nudix protein Nudt12 is a second mammalian deNADding enzyme structurally and mechanistically distinct from DXO and targets different RNAs. Crystal structure of mouse Nudt12 in complex with the deNADding product AMP and three Mg2+ ions at 1.6 [A] resolution provides exquisite insights into the molecular basis of the deNADding activity within the NAD pyrophosphate. Disruption of the Nudt12 gene stabilizes transfected NAD-capped RNA in cells and its endogenous NAD-capped mRNA targets are enriched in those encoding proteins involved in cellular energetics. Furthermore, exposure of cells to metabolic stress manifests changes in NAD-capped RNA levels indicating an association between NAD-capped RNAs and cellular metabolism. Lastly, we show that the bacterial RppH protein also possesses deNADding activity toward NAD-capped RNA but not free NAD, revealing a third class of deNADding enzymes.

molecular biology↗

bioRxiv2018

A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase

Success in precision medicine depends on our ability to determine which rare human genetic variants have functional effects. Classical homocystinuria--characterized by elevated homocyst(e)ine in plasma and urine--is caused by primarily-rare variants in the cystathionine beta-synthase (CBS) gene. About half of patients respond to vitamin B6 therapy. With early detection in newborns, existing therapies are highly effective. Functional CBS variants, especially those that respond to vitamin B6, can be detected based on their ability to restore growth in yeast cells lacking CYS4 (the yeast ortholog of CBS). This assay has previously been carried out only reactively after first observation of a variant in patients. Here we describe a proactive comprehensive missense variant effect map for human CBS. Together, saturation codon-replacement mutagenesis, en masse growth selection at different vitamin B6 levels, and sequencing yielded a look-up table for CBS missense variant function and vitamin B6-remediability in yeast. The CBS variant effect map identified disease variants and predicted both disease severity (r = 0.82) and human clinical response to vitamin B6 (r = 0.89). Thus, highly-multiplexed cell-based assays can yield proactive maps of variant function and patient response to therapy, even for rare variants not previously seen in the clinic.

genetics↗

bioRxiv2018

Colonization of the tsetse fly midgut with commensal Enterobacter inhibits trypanosome infection establishment

Tsetse flies (Glossina spp.) vector pathogenic trypanosomes (Trypanosoma spp.) in sub-Saharan Africa. These parasites cause human and animal African trypanosomiases, which are debilitating diseases that inflict an enormous socio-economic burden on inhabitants of endemic regions. Current disease control strategies rely primarily on treating infected animals and reducing tsetse population densities. However, relevant programs are costly, labor intensive and difficult to sustain. As such, novel strategies aimed at reducing tsetse vector competence require development. Herein we investigated whether an Enterobacter bacterium (Esp_Z), which confers Anopheles gambiae with resistance to Plasmodium, is able to colonize tsetse and induce a trypanosome refractory phenotype in the fly. Esp_Z established stable infections in tsetses gut, and exhibited no adverse effect on the survival of individuals from either group. Flies with established Esp_Z infections in their gut were significantly more refractory to infection with two distinct trypanosome species (T. congolense, 6% infection; T. brucei, 32% infection) than were age-matched flies that did not house the exogenous bacterium (T. congolense, 36% infected; T. brucei, 70% infected). Additionally, 52% of Esp_Z colonized tsetse survived infection with entomopathogenic Serratia marcescens, compared with only 9% of their wild-type counterparts. These parasite and pathogen refractory phenotypes result from the fact that Esp_Z acidifies tsetses midgut environment, which inhibits trypanosome and Serratia growth and thus infection establishment. Finally, we determined that Esp_Z infection does not impact the fecundity of male or female tsetse, nor the ability of male flies to compete with their wild-type counterparts for mates. We propose that Esp_Z could be used as one component of an integrated strategy aimed at reducing the ability of tsetse to transmit pathogenic trypanosomes.\n\nAuthor SummaryTsetse flies transmit pathogenic African trypanosomes, which are the causative agents of socio-economically devastating human and animal African trypanosomiases. These diseases are currently controlled in large part by reducing the population size of tsetse vectors through the use of insecticides, traps and sterile insect technique. However, logistic and monetary hurdles often preclude the prolonged application of procedures necessary to maintain these control programs. Thus, novel strategies, including those aimed at sustainably reducing the ability of tsetse to transmit trypanosomes, are presently under development. Herein we stably colonize tsetse flies with a bacterium (Enterobacter sp. Z, Esp_Z) that acidifies their midgut, thus rendering the environment inhospitable to infection with two distinct, epidemiologically important trypanosome strains as well as an entomopathogenic bacteria. In addition to inducing a trypanosome refractory phenotype, colonization of tsetse with Esp_Z exerts only a modest fitness cost on the fly. Taken together, these findings suggest that Esp_Z could be applied to enhance the effectiveness of currently employed tsetse control programs.

microbiology↗

bioRxiv2018

Amino Acids Changes and Muscle Damage During the 400 km Ultra Trail Gobi Race

Current researches demonstrated that completing the Ultra Trail Gobi (UTG) could lead to severe muscle damage. Our study was designed to analysis the muscle damage and amino acid changes reacted to a 400 km ultra-endurance race in experienced runners. Peripheral blood samples from 16 male athletes (mean age 40.3 {+/-} 7.0 years, mean finish time 121.2 {+/-} 21.8 hours), taken 48 h before and immediately after completing the Ultra Trail Gobi Race (UTG), were analyzed for 39 amino acids, 15 steroid hormones and 4 muscle damage factors. In all participants, the 4 biomarkers for muscle damage, i.e., creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increased significantly after the race, whose mean post-race values were 13.7-, 7.3-, 4.7- and 1.5-fold higher than the pre-race values, respectively. 5 amino acids, i.e., alanine, valine, proline, ornithine and citrulline showed significant decrease, whose mean values decreased by 40.4 {+/-} 18.7%, 38.9 {+/-} 9.3%, 48.1 {+/-} 15.2%, 44.8 {+/-} 15.1% and 23.4 {+/-} 30.8% after the race, respectively. Our study revealed that progressive decline in amino acids contents may further contribute to the factors increasing the muscle damage during the UTG.

physiology↗

bioRxiv2018

Anterior insular cortex plays a critical role in interoceptive attention

Although accumulating evidence indicates that the anterior insular cortex (AIC) mediates interoceptive attention, which refers the attention towards physiological signals arising from the body, the necessity of the AIC in this process has not been demonstrated. Using a novel task that directs attention toward breathing rhythm, we assessed the involvement of the AIC in interoceptive attention in healthy participants using functional magnetic resonance imaging and examined the necessity of the AIC in interoceptive attention in patients with AIC lesions. We found that interoceptive attention was associated with greater AIC activation, as well as enhanced coupling between the AIC and somatosensory area along with reduced coupling between AIC and visual sensory areas. AIC activation and connectivity were predictive of individual differences in interoceptive accuracy. Importantly, AIC lesion patients showed disrupted interoceptive discrimination accuracy and sensitivity. Together, these results provide compelling evidence that AIC plays a critical role in interoceptive attention.

neuroscience↗

bioRxiv2018

Antibacterial activity of total flavonoids from Ilex rotunda Thunb. and different antibacterials on different multidrug-resistant bacteria alone or in combination

The problem of bacterial resistance is becoming more and more serious, which has become an urgent problem to be solved in human and veterinary. One approach to control and delay bacterial resistance is combination therapy in which antibiotics are given together with other antimicrobial or non-antimicrobial agents. Studies have shown that flavonoids from Traditional Chinese medicine (TCM) possess a high level of antibacterial activity against antibiotic resistant strains. The aim of this study was to evaluate the antibacterial effects of a combined therapy of total flavonoids from Ilex rotunda Thunb. and antibiotics against seven kinds of veterinary bacteria which were multidrug resistance bacteria. A microdilution checkerboard method was used to determine the minimal inhibitory concentrations of both types of antimicrobials, alone and in combination. The fractional inhibitory concentration index was calculated and used to classify observed collective antibacterial activity as synergistic, additive, indifferent or antagonistic.\n\nFrom the performed tests, the total flavonoids and antimicrobial agents were combined to inhibit different multidrug-resistant bacteria, such as Escherichia coli, Streptococcus, Pseudomonas aeruginosa, Enterococcus faecalis, Proteus vulgaris, Staphylococcus aureus, Acinetobacter baumannii. For these bacteria, total flavonoids from Ilex Rotunda Thunb. presented synergistic or additive with different antibiotics and had a certain antibacterial effect on the separated multidrug-resistant bacteria. The study shows total flavonoids from Ilex rotunda Thunb. have potential as adjuvants for the treatment of animal bacterial diseases.

microbiology↗

bioRxiv2018

JHU-2545 Selectively Shields Salivary Glands and Kidneys during PSMA-Targeted Radiotherapy

PURPOSEProstate-specific membrane antigen (PSMA) radiotherapy is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC) with several beta or alpha particle-emitting radionuclide-conjugated small molecules showing efficacy in late stage patients. However, PSMA is also expressed in kidneys and salivary glands where specific uptake causes dose-limiting xerostomia and potential for nephrotoxicity. The PSMA inhibitor 2- (phosphonomethyl)pentanedioic acid (2-PMPA) can prevent kidney uptake in mice, but also blocks tumor uptake, precluding its clinical utility. Selective delivery of 2-PMPA to non-malignant tissues could improve the therapeutic window of PSMA radiotherapy. EXPERIMENTAL DESIGNA tri-alkoxycarbonyloxy alkyl (TrisPOC) prodrug of 2-PMPA, JHU-2545, was synthesized to enhance 2-PMPA delivery to non-malignant tissues. Preclinical pharmacokinetic and imaging experiments were conducted prior to assessment in 3 mCRPC patients receiving PSMA PET and radiotherapy. RESULTSJHU-2545 resulted in 3- and 53-fold greater exposure of 2-PMPA in rodent salivary glands (18.0 {+/-} 0.97 h*nmol/g) and kidneys (359 {+/-} 4.16 h*nmol/g) versus prostate tumor xenograft (6.79 {+/-} 0.19 h*nmol/g). JHU-2545 also blocked rodent kidneys and salivary glands uptake of the PSMA PET tracers 68Ga-PSMA-11 and 18F-DCFPyL by up to 85% without effect on tumor. In a mCRPC patient, JHU-2545 treatment prior to 68Ga-PSMA-617 administration reduced kidney SUVmax by 76% without effect on metastatic lesions. When administered prior to injection of the beta emitter 177Lu-PSMA-617, JHU-2545 shielded both the salivary glands (72% Gy reduction) and kidneys (45% Gy reduction) without effect on metastases dose. CONCLUSIONSJHU-2545 pre-treatment raises the cumulative dose limit and improves the safety and efficacy profile of PSMA radiotherapy. STATEMENT OF TRANSLATIONAL RELEVANCEProstate Specific Membrane Antigen (PSMA) molecular radiotherapy has emerged as a promising treatment for metastatic castration-resistant prostate cancer (mCRPC), but endogenous expression of PSMA in kidneys and salivary glands causes uptake into these organs resulting in dose-limiting toxicities. We describe the discovery of JHU-2545, a PSMA inhibitor prodrug that selectively blocks kidney and salivary gland uptake of PSMA theranostics without altering tumor uptake in both preclinical models and in mCRPC patients. Pretreatment of JHU-2545 thereby improves the safety and efficacy profile of the multiple PSMA radiotherapies in development.

pharmacology and toxicology↗

bioRxiv2018

CSTDB: A Crop Stress-tolerance Gene and Protein Database Integrated by Convolutional Neural Networks

Numerous studies have shown that many genes and proteins in plants are involved in the regulation of plant resistance to abiotic and biotic stresses. The researches on the stress tolerance of crops are also the focus of many researchers. To provides a reliable platform for collecting and retrieving genetic and protein information related to stress tolerance found in crops, we constructed CSTDB(Crops Stress-tolerance Database), an integrated database that includes stress-tolerance genes and proteins for many crop species. The database was developed based on convolutional neural network technology. It is a web-accessible database that contains detailed information on the stress-tolerance genes and proteins of major crop species. Currently, the database records four major crops containing 1,371 abiotic stress-tolerance genes or proteins, and 207 genes or proteins associated with biotic stress. Each gene and protein has detailed functional information and sequence information, such as stress types, Genbank ID, Pubmed ID, Protein ID, 3D model picture and FASTA files. As a user-friendly browsing tool, this database provides search functions, BALST functions and file download functions. CSTDB can be a valuable resource, which is designed to meet the broad needs of researchers working on crops stress-tolerance experiments. Database URL: http://pcsb.ahau.edu.cn:8080/CSTDB

bioinformatics↗

bioRxiv2018

Cytologic, Genetic, and Proteomic Analysis of a Yellow Leaf Mutant of Sesame (Sesamum indicum L.), Siyl-1

Leaf color mutation in sesame always affects the growth and development of plantlets, and their yield. To clarify the mechanisms underlying leaf color regulation in sesame, we analyzed a yellow-green leaf mutant. Genetic analysis of the mutant selfing revealed 3 phenotypes--YY, light-yellow (lethal); Yy, yellow-green; and yy, normal green--controlled by an incompletely dominant nuclear gene, Siyl-1. In YY and Yy, the number and morphological structure of the chloroplast changed evidently, with disordered inner matter, and significantly decreased chlorophyll content. To explore the regulation mechanism of leaf color mutation, the proteins expressed among YY, Yy, and yy were analyzed. All 98 differentially expressed proteins (DEPs) were classified into 5 functional groups, in which photosynthesis and energy metabolism (82.7%) occupied a dominant position. Our findings provide the basis for further molecular mechanism and biochemical effect analysis of yellow leaf mutants in plants.

genetics↗

bioRxiv2018

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Birth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individuals own genotype on BW and subsequent disease risk from indirect effects of their mothers correlated genotype, mediated by the intrauterine environment. Here, we describe expanded genome-wide association analyses of own BW (n=321,223) and offspring BW (n=230,069 mothers), which identified 278 independent association signals influencing BW (214 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic influences on BW, implicating fetal- and maternal-specific mechanisms. We used Mendelian randomization to explore the causal relationships between factors influencing BW through fetal or maternal routes, for example, glycemic traits and blood pressure. Direct fetal genotype effects dominate the shared genetic contribution to the association between lower BW and higher type 2 diabetes risk, whereas the relationship between lower BW and higher later blood pressure (BP) is driven by a combination of indirect maternal and direct fetal genetic effects: indirect effects of maternal BP-raising genotypes act to reduce offspring BW, but only direct fetal genotype effects (once inherited) increase the offsprings later BP. Instrumental variable analysis using maternal BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring BP. In successfully separating fetal from maternal genetic effects, this work represents an important advance in genetic studies of perinatal outcomes, and shows that the association between lower BW and higher adult BP is attributable to genetic effects, and not to intrauterine programming.

genetics↗