Success in life is linked to executive functions, a collection of cognitive processes that support goal-directed behaviors. Executive functions is an umbrella term related to cognitive control, self-control, and more. Variations in executive functioning predict concurrent success in schooling, relationships, and behavior, as well as important life outcomes years later. Such findings may suggest that certain individuals are destined for good executive functioning and success. However, environmental influences on executive function and development have long been recognized. Recent research in this tradition demonstrates the power of social contextual influences on children\'s engagement of executive functions. Such findings suggest new interpretations of why individuals differ in executive functioning and associated life outcomes, including across cultures and socioeconomic statuses. These findings raise fundamental questions about how best to conceptualize, measure, and support executive functioning across diverse contexts. Future research addressing real-world dynamics and computational mechanisms will elucidate how executive functioning emerges in the world.

BACKGROUND: Epigenetic clocks were known as promising biomarkers of aging, including original clocks trained by individual CpG sites and principal component (PC) clocks trained by PCs of CpG sites. The effects of genetic and environmental factors on epigenetic clocks are still unclear, especially for PC clocks.
METHODS: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs.
RESULTS: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks.
CONCLUSIONS: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks.

Intracranial volume (ICV) reflects maximal brain development and is associated with later-life cognitive abilities. We quantified ICV among first- and second-generation Hispanic and Latino adults from the Study of Latinos-Investigation of Cognitive Aging - MRI (SOL-INCA-MRI), estimated ICV heritability, and tested its associations with previously reported genetic variants, both individually and as a genetic risk score (GRS). We also estimated the association of ICV with early life environmental measures: nativity or age of immigration and parental education. The estimated heritability of ICV was 19% (95% CI, 0.1%-56%) in n=1781 unrelated SOL-INCA-MRI individuals. Four of 10 tested genetic variants were associated with ICV and an increase of 1 SD of the ICV-GRS was associated with an increase of 10.37 cm3 in the ICV (95% CI, 5.29-15.45). Compared to being born in the continental United States, immigrating to the United States at age 11 years or older was associated with 24 cm3 smaller ICV (95% CI, -39.97 to -8.06). Compared to both parents having less than high-school education, at least 1 parent completing high-school education was associated with 15.4 cm3 greater ICV (95% CI, 4.46-26.39). These data confirm the importance of early life health on brain development.

BACKGROUND: Population stratification based on interindividual variability in gut microbiota composition has revealed the existence of several ecotypes named enterotypes in humans and various animal species. Enterotypes are often associated with environmental factors including diet, but knowledge of the role of host genetics remains scarce. Moreover, enterotypes harbor functionalities likely associated with varying abilities and susceptibilities of their host. Previously, we showed that under controlled conditions, 60-day-old pig populations consistently split into two enterotypes with either Prevotella and Mitsuokella (PM enterotype) or Ruminococcus and Treponema (RT enterotype) as keystone taxa. Here, our aim was to rely on pig as a model to study the influence of host genetics to assemble enterotypes, and to provide clues on enterotype functional differences and their links with growth traits.
RESULTS: We established two pig lines contrasted for abundances of the genera pairs specifying each enterotype at 60 days of age and assessed them for fecal microbiota composition and growth throughout three consecutive generations. Response to selection across three generations revealed, per line, an increase in the prevalence of the selected enterotype and in the average relative abundances of directly and indirectly selected bacterial genera. The PM enterotype was found less diverse than the RT enterotype but more efficient for piglet growth during the post-weaning period. Shotgun metagenomics revealed differentially abundant bacterial species between the two enterotypes. By using the KEGG Orthology database, we show that functions related to starch degradation and polysaccharide metabolism are enriched in the PM enterotype, whereas functions related to general nucleoside transport and peptide/nickel transport are enriched in the RT enterotype. Our results also suggest that the PM and RT enterotypes might differ in the metabolism of valine, leucin, and isoleucine, favoring their biosynthesis and degradation, respectively.
CONCLUSIONS: We experimentally demonstrated that enterotypes are functional ecosystems that can be selected as a whole by exerting pressure on the host genetics. We also highlight that holobionts should be considered as units of selection in breeding programs. These results pave the way for a holistic use of host genetics, microbiota diversity, and enterotype functionalities to understand holobiont shaping and adaptation. Video Abstract.

Introduction: Pubertal attainment is critical to reproductive longevity in heifers. Previously, four heifer pubertal classifications were identified according to attainment of blood plasma progesterone concentrations > 1 ng/ml: 1) Early; 2) Typical; 3) Start-Stop; and 4) Non-Cycling. Early and Typical heifers initiated and maintained cyclicity, Start-Stop started and then stopped cyclicity and Non-Cycling never initiated cyclicity. Start-Stop heifers segregated into Start-Stop-Discontinuous (SSD) or Start-Stop-Start (SSS), with SSD having similar phenotypes to Non-Cycling and SSS to Typical heifers. We hypothesized that these pubertal classifications are heritable, and loci associated with pubertal classifications could be identified by genome wide association studies (GWAS). Methods: Heifers (n = 532; 2017 - 2022) genotyped on the Illumina Bovine SNP50 v2 or GGP Bovine 100K SNP panels were used for variant component estimation and GWAS. Heritability was estimated using a univariate Bayesian animal model. Results: When considering pubertal classifications: Early, Typical, SSS, SSD, and Non-Cycling, pubertal class was moderately heritable (0.38 ± 0.08). However, when heifers who initiated and maintained cyclicity were compared to those that did not cycle (Early+Typical vs. SSD+Non-Cycling) heritability was greater (0.59 ± 0.19). A GWAS did not identify single nucleotide polymorphisms (SNPs) significantly associated with pubertal classifications, indicating puberty is a polygenic trait. A candidate gene approach was used, which fitted SNPs within or nearby a set of 71 candidate genes previously associated with puberty, PCOS, cyclicity, regulation of hormone secretion, signal transduction, and methylation. Eight genes/regions were associated with pubertal classifications, and twenty-two genes/regions were associated with whether puberty was attained during the trial. Additionally, whole genome sequencing (WGS) data on 33 heifers were aligned to the reference genome (ARS-UCD1.2) to identify variants in FSHR, a gene critical to pubertal attainment. Fisher\'s exact test determined if FSHR SNPs segregated by pubertal classification. Two FSHR SNPs that were not on the bovine SNP panel were selected for additional genotyping and analysis, and one was associated with pubertal classifications and whether they cycled during the trial. Discussion: In summary, these pubertal classifications are moderately to highly heritable and polygenic. Consequently, genomic tools to inform selection/management of replacement heifers would be useful if informed by SNPs associated with cyclicity and early pubertal attainment.

BACKGROUND: Drought adaptation is critical to many tree species persisting under climate change, however our knowledge of the genetic basis for trees to adapt to drought is limited. This knowledge gap impedes our fundamental understanding of drought response and application to forest production and conservation. To improve our understanding of the genomic determinants, architecture, and trait constraints, we assembled a reference genome and detected ~ 6.5 M variants in 432 phenotyped individuals for the foundational tree Corymbia calophylla.
RESULTS: We found 273 genomic variants determining traits with moderate heritability (h2SNP = 0.26-0.64). Significant variants were predominantly in gene regulatory elements distributed among several haplotype blocks across all chromosomes. Furthermore, traits were constrained by frequent epistatic and pleiotropic interactions.
CONCLUSIONS: Our results on the genetic basis for drought traits in Corymbia calophylla have several implications for the ability to adapt to climate change: (1) drought related traits are controlled by complex genomic architectures with large haplotypes, epistatic, and pleiotropic interactions; (2) the most significant variants determining drought related traits occurred in regulatory regions; and (3) models incorporating epistatic interactions increase trait predictions. Our findings indicate that despite moderate heritability drought traits are likely constrained by complex genomic architecture potentially limiting trees response to climate change.

UNASSIGNED: The Human Connectome Project (HCP) has become a keystone dataset in human neuroscience, with a plethora of important applications in advancing brain imaging methods and an understanding of the human brain. We focused on tractometry of HCP diffusion-weighted MRI (dMRI) data.
UNASSIGNED: We used an open-source software library (pyAFQ; https://yeatmanlab.github.io/pyAFQ) to perform probabilistic tractography and delineate the major white matter pathways in the HCP subjects that have a complete dMRI acquisition (n = 1,041). We used diffusion kurtosis imaging (DKI) to model white matter microstructure in each voxel of the white matter, and extracted tract profiles of DKI-derived tissue properties along the length of the tracts. We explored the empirical properties of the data: first, we assessed the heritability of DKI tissue properties using the known genetic linkage of the large number of twin pairs sampled in HCP. Second, we tested the ability of tractometry to serve as the basis for predictive models of individual characteristics (e.g., age, crystallized/fluid intelligence, reading ability, etc.), compared to local connectome features. To facilitate the exploration of the dataset we created a new web-based visualization tool and use this tool to visualize the data in the HCP tractometry dataset. Finally, we used the HCP dataset as a test-bed for a new technological innovation: the TRX file-format for representation of dMRI-based streamlines.
UNASSIGNED: We released the processing outputs and tract profiles as a publicly available data resource through the AWS Open Data program\'s Open Neurodata repository. We found heritability as high as 0.9 for DKI-based metrics in some brain pathways. We also found that tractometry extracts as much useful information about individual differences as the local connectome method. We released a new web-based visualization tool for tractometry-\"Tractoscope\" (https://nrdg.github.io/tractoscope). We found that the TRX files require considerably less disk space-a crucial attribute for large datasets like HCP. In addition, TRX incorporates a specification for grouping streamlines, further simplifying tractometry analysis.

Spurs, which mainly appear in roosters, are protrusions near the tarsometatarsus on both sides of the calves of chickens, and are connected to the tarsometatarsus by a bony core. As a male-biased morphological characteristic, the diameter and length of spurs vary significantly between different individuals, mainly related to genetics and age. As a specific behavior of hens, egg-laying also varies greatly between individuals in terms of traits such as age at first egg (AFE), egg weight (EW), and so on. At present, there are few studies on chicken spurs. In this study, we investigated the inheritance pattern of the spur trait in roosters with different phenotypes and the correlations between spur length, body weight at 18 weeks of age (BW18), shank length at 18 weeks of age (SL18), and the egg-laying trait in hens (both hens and roosters were from the same population and were grouped according to their family). These traits related to egg production included AFE, body weight at first egg (BWA), and first egg weight (FEW). We estimated genetic parameters based on pedigree and phenotype data, and used variance analysis to calculate broad-sense heritability for correcting the parameter estimation results. The results showed that the heritability of male left and right spurs ranged from 0.6 to 0.7. There were significant positive correlations between left and right spur length, BW18, SL18, and BWA, as well as between left and right spur length and AFE. We selected 35 males with the longest spurs and 35 males with the shortest spurs in the population, and pooled them into two sets to obtain the pooled genome sequencing data. After genome-wide association and genome divergency analysis by FST, allele frequency differences (AFDs), and XPEHH methods, we identified 7 overlapping genes (CENPE, FAT1, FAM149A, MANBA, NFKB1, SORBS2, UBE2D3) and 14 peak genes (SAMD12, TSPAN5, ENSGALG00000050071, ENSGALG00000053133, ENSGALG00000050348, CNTN5, TRPC6, ENSGALG00000047655,TMSB4X, LIX1, CKB, NEBL, PRTFDC1, MLLT10) related to left and right spur length through genome-wide selection signature analysis and a genome-wide association approach. Our results identified candidate genes associated with chicken spurs, which helps to understand the genetic mechanism of this trait and carry out subsequent research around it.

Egg production plays a pivotal role in the economic viability of hens. To analyze the genetic rules of egg production, a total of 3151 Luhua chickens were selected, the egg production traits including egg weight at first laying (Start-EW), egg weight at 43 weeks (EW-43), egg number at 43 weeks (EN-43), and total egg number (EN-All) were recorded. Then, the effects of related factors on egg production traits were explored, using a multi-trait animal model for genetic parameter estimation and a genome-wide association study (GWAS). The results showed that body weight at first egg (BWFE), body weight at 43 weeks (BW-43), age at first egg (AFE), and seasons had significant effects on the egg production traits. Start-EW and EW-43 had moderate heritability of 0.30 and 0.21, while EN-43 and EN-All had low heritability of 0.13 and 0.16, respectively. Start-EW exhibited a robust positive correlation with EW-43, while Start-EW was negatively correlated with EN-43 and EN-All. Furthermore, gene ontology (GO) results indicated that Annexin A2 (ANXA2) and Frizzled family receptor 7 (FZD7) related to EW-43, Cyclin D1 (CCND1) and A2B adenosine receptor (ADORA2B) related to EN-All, and have been found to be mainly involved in metabolism and growth processes, and deserve more attention and further study. This study contributes to accelerating genetic progress in improving low heritability egg production traits in layers, especially in Luhua chickens.

LD score regression (LDSC) is a method to estimate narrow-sense heritability from genome-wide association study (GWAS) summary statistics alone, making it a fast and popular approach. In this work, we present interaction-LD score (i-LDSC) regression: an extension of the original LDSC framework that accounts for interactions between genetic variants. By studying a wide range of generative models in simulations, and by re-analyzing 25 well-studied quantitative phenotypes from 349,468 individuals in the UK Biobank and up to 159,095 individuals in BioBank Japan, we show that the inclusion of a cis-interaction score (i.e. interactions between a focal variant and proximal variants) recovers genetic variance that is not captured by LDSC. For each of the 25 traits analyzed in the UK Biobank and BioBank Japan, i-LDSC detects additional variation contributed by genetic interactions. The i-LDSC software and its application to these biobanks represent a step towards resolving further genetic contributions of sources of non-additive genetic effects to complex trait variation.