Vertical transmission of bacteria from mother to infant at birth is postulated to initiate a life-long host-microbe symbiosis, playing an important role in early infant development. However, only the ...tracking of strictly defined unique microbial strains can clarify where the intestinal bacteria come from, how long the initial colonizers persist, and whether colonization by other strains from the environment can replace existing ones. Using rare single nucleotide variants in fecal metagenomes of infants and their family members, we show strong evidence of selective and persistent transmission of maternal strain populations to the vaginally born infant and their occasional replacement by strains from the environment, including those from family members, in later childhood. Only strains from the classes Actinobacteria and Bacteroidia, which are essential components of the infant microbiome, are transmitted from the mother and persist for at least 1 yr. In contrast, maternal strains of Clostridia, a dominant class in the mother's gut microbiome, are not observed in the infant. Caesarean-born infants show a striking lack of maternal transmission at birth. After the first year, strain influx from the family environment occurs and continues even in adulthood. Fathers appear to be more frequently donors of novel strains to other family members than receivers. Thus, the infant gut is seeded by selected maternal bacteria, which expand to form a stable community, with a rare but stable continuing strain influx over time.
Abstract
Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast, monozygotic (MZ) twins occur ...at a constant rate across time and geographical regions and, with some rare exceptions, do not cluster in families. The leading hypothesis for MZ twins, which arise when a zygote splits during preimplantation stages of development, is random occurrence. We have found the first series of genes underlying the liability of being the mother of DZ twins and have shown that being an MZ twin is strongly associated with a stable DNA methylation signature in child and adult somatic tissues. Because identical twins keep this molecular signature across the lifespan, this discovery opens up completely new possibilities for the retrospective diagnosis of whether a person is an MZ twin whose co-twin may have vanished in the early stages of pregnancy. Here, we summarize the gene finding results for mothers of DZ twins based on genetic association studies followed by meta-analysis, and further present the striking epigenetic results for MZ twins.
Graphical Abstract
Graphical Abstract
Recent findings regarding the genetic susceptibility to being the mother of dizygotic (DZ) twins (top) and an epigenetic signature associated with being a monozygotic (MZ) twin (bottom). TGC (logo): Twinning Genetics Consortium; SNP: single-nucleotide polymorphism.
Aesthetic chills, broadly defined as a somatic marker of peak emotional-hedonic responses, are experienced by individuals across a variety of human cultures. Yet individuals vary widely in the ...propensity of feeling them. These individual differences have been studied in relation to demographics, personality, and neurobiological and physiological factors, but no study to date has explored the genetic etiological sources of variation. To partition genetic and environmental sources of variation in the propensity of feeling aesthetic chills, we fitted a biometrical genetic model to data from 14,127 twins (from 8995 pairs), collected by the Netherlands Twin Register. Both genetic and unique environmental factors accounted for variance in aesthetic chills, with heritability estimated at 0.36 (0.33, 0.39 95% CI). We found females more prone than males to report feeling aesthetic chills. However, a test for genotype x sex interaction did not show evidence that heritability differs between sexes. We thus show that the propensity of feeling aesthetic chills is not shaped by nurture alone, but it also reflects underlying genetic propensities.
Evolutionary mechanisms for loneliness Cacioppo, John T.; Cacioppo, Stephanie; Boomsma, Dorret I.
Cognition and emotion,
01/2014, Letnik:
28, Številka:
1
Journal Article
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Robert Weiss (1973) conceptualised loneliness as perceived social isolation, which he described as a gnawing, chronic disease without redeeming features. On the scale of everyday life, it is ...understandable how something as personally aversive as loneliness could be regarded as a blight on human existence. However, evolutionary time and evolutionary forces operate at such a different scale of organisation than we experience in everyday life that personal experience is not sufficient to understand the role of loneliness in human existence. Research over the past decade suggests a very different view of loneliness than suggested by personal experience, one in which loneliness serves a variety of adaptive functions in specific habitats. We review evidence on the heritability of loneliness and outline an evolutionary theory of loneliness, with an emphasis on its potential adaptive value in an evolutionary timescale.
Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD ...comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.
We introduce two novel methods for multivariate genome-wide-association meta-analysis (GWAMA) of related traits that correct for sample overlap. A broad range of simulation scenarios supports the ...added value of our multivariate methods relative to univariate GWAMA. We applied the novel methods to life satisfaction, positive affect, neuroticism, and depressive symptoms, collectively referred to as the well-being spectrum (N
= 2,370,390), and found 304 significant independent signals. Our multivariate approaches resulted in a 26% increase in the number of independent signals relative to the four univariate GWAMAs and in an ~57% increase in the predictive power of polygenic risk scores. Supporting transcriptome- and methylome-wide analyses (TWAS and MWAS, respectively) uncovered an additional 17 and 75 independent loci, respectively. Bioinformatic analyses, based on gene expression in brain tissues and cells, showed that genes differentially expressed in the subiculum and GABAergic interneurons are enriched in their effect on the well-being spectrum.
Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial ...consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.
Loneliness typically refers to the feelings of distress and dysphoria resulting from a discrepancy between a person's desired and achieved levels of social relations, and there is now considerable ...evidence that loneliness is a risk factor for poor psychological and physical health. Loneliness has traditionally been conceptualized as a uniquely human phenomenon. However, over millions of years of evolution, efficient and manifold neural, hormonal, and molecular mechanisms have evolved for promoting companionship and mutual protection/assistance and for organizing adaptive responses when there is a significant discrepancy between the preferred and realized levels of social connection. We review evidence suggesting that loneliness is not a uniquely human phenomenon, but, instead, as a scientific construct, it represents a generally adaptive predisposition that can be found across phylogeny. Central to this argument is the premise that the brain is the key organ of social connections and processes. Comparative studies and animal models, particularly when integrated with human studies, have much to contribute to the understanding of loneliness and its underlying principles, mechanisms, consequences, and potential treatments.
Estimates from Mendelian randomization studies of unrelated individuals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian ...randomization analyses and use simulation studies to show that family-based analyses can reduce such biases. We illustrate empirically how familial effects can affect estimates using data from 61,008 siblings from the Nord-Trøndelag Health Study and UK Biobank and replicated our findings using 222,368 siblings from 23andMe. Both Mendelian randomization estimates using unrelated individuals and within family methods reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while Mendelian randomization estimates from samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects were strongly attenuated in within-family Mendelian randomization analyses. Our findings indicate the necessity of controlling for population structure and familial effects in Mendelian randomization studies.
The human brain is active during rest and hierarchically organized into intrinsic functional networks. These functional networks are largely established early in development, with reports of a shift ...from a local to more distributed organization during childhood and adolescence. It remains unknown to what extent genetic and environmental influences on functional connectivity change throughout adolescent development. We measured functional connectivity within and between eight cortical networks in a longitudinal resting-state fMRI study of adolescent twins and their older siblings on two occasions (mean ages 13 and 18 years). We modelled the reliability for these inherently noisy and head-motion sensitive measurements by analyzing data from split-half sessions. Functional connectivity between resting-state networks decreased with age whereas functional connectivity within resting-state networks generally increased with age, independent of general cognitive functioning. Sex effects were sparse, with stronger functional connectivity in the default mode network for girls compared to boys, and stronger functional connectivity in the salience network for boys compared to girls. Heritability explained up to 53% of the variation in functional connectivity within and between resting-state networks, and common environment explained up to 33%. Genetic influences on functional connectivity remained stable during adolescent development. In conclusion, longitudinal age-related changes in functional connectivity within and between cortical resting-state networks are subtle but wide-spread throughout adolescence. Genes play a considerable role in explaining individual variation in functional connectivity with mostly stable influences throughout adolescence.
•We studied resting-state networks in a longitudinal adolescent twin-sibling sample.•Functional connectivity shows age-related increases within resting-state networks.•Functional connectivity shows age-related decreases between resting-state networks.•Reliability modelling improves sensitivity to detect familial influences.•Genetic influences on functional connectivity remain stable throughout adolescence.
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