Project description:BackgroundThe early life of the human host marks a critically important time for establishment of the gut microbial community, yet the developmental trajectory of gut community-encoded resistance genes (resistome) is unknown. We present a longitudinal study of the fecal antibiotic resistome of healthy amoxicillin-exposed and antibiotic-naive twins and their mothers during the first year of life.ResultsWe extracted metagenomic DNA (mgDNA) from fecal samples collected from three healthy twin pairs at three timepoints (1 or 2 months, 6 or 7 months, and 11 months) and from their mothers (collected at delivery). The mgDNA was used to construct metagenomic expression libraries in an Escherichia coli host. These libraries were screened for antibiotic resistance, and functionally selected resistance genes were sequenced and annotated. A diverse fecal resistome distinct from the maternal resistome was apparent by 2 months of age, and infants' fecal resistomes included resistance to clinically important broad-spectrum beta-lactam antibiotics (e.g., piperacillin-tazobactam, aztreonam, cefepime) not found in their mothers. Dissemination of resistance genes among members of a given family was positively correlated with sharing of those same resistance genes between unrelated families, potentially identifying within-family sharing as a marker of resistance genes emerging in the human community at large. Finally, we found a distinct developmental trajectory for a community-encoded function: chloramphenicol resistance. All study subjects at all timepoints harbored chloramphenicol resistance determinants, but multidrug efflux pumps (rarely found in mothers) were the primary effectors of chloramphenicol resistance in young infants. Chloramphenicol acetyltransferases were more common in mothers than in infants and were found in nearly all the infants at later timepoints.ConclusionsOur results suggest that healthy 1-2-month-old infants' gut microbes harbor clinically relevant resistance genes distinct from those of their mothers, and that family-specific shared environmental factors early in life shape resistome development.

Project description:BackgroundAlthough polygenic risk scores (PRS) predict psychiatric problems, these associations might be attributable to indirect pathways including population stratification, assortative mating, or dynastic effects (mediation via parental environments). The goal of this study was to examine whether PRS-psychiatric symptom associations were attributable to indirect versus direct pathways.MethodsThe sample consisted of 3,907 dizygotic (DZ) twin pairs. In childhood, their parents rated them on 98 symptoms. In adolescence (n = 2,393 DZ pairs), both the parents and the twins rated themselves on 20 symptoms. We extracted one general and seven specific factors from the childhood data, and one general and three specific factors from the adolescent data. We then regressed each general factor model onto ten psychiatric PRS simultaneously. We first conducted the regressions between individuals (β) and then within DZ twin pairs (βw ), which controls for indirect pathways.ResultsIn childhood, the PRS for ADHD predicted general psychopathology (β = 0.09, 95% CI: [0.06, 0.12]; βw = 0.07 [0.01, 0.12]). Furthermore, the PRS for ADHD predicted specific inattention (β = 0.04 [0.00, 0.08]; βw = 0.09 [0.01, 0.17]) and specific hyperactivity (β = 0.07 [0.04, 0.11]; βw = 0.09 [0.01, 0.16]); the PRS for schizophrenia predicted specific learning (β = 0.08 [0.03, 0.13]; βw = 0.19 [0.08, 0.30]) and specific inattention problems (β = 0.05 [0.01, 0.09]; βw = 0.10 [0.02, 0.19]); and the PRS for neuroticism predicted specific anxiety (β = 0.06 [0.02, 0.10]; βw = 0.06 [0.00, 0.12]). Overall, the PRS-general factor associations were similar between individuals and within twin pairs, whereas the PRS-specific factors associations amplified by 84% within pairs.ConclusionsThis implies that PRS-psychiatric symptom associations did not appear attributable to indirect pathways such as population stratification, assortative mating, or mediation via parental environments. Rather, genetics appeared to directly influence symptomatology.

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Using twin-pairs to assess potential bias in polygenic prediction of externalising behaviours across development.

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Using twin-pairs to assess potential bias in polygenic prediction of externalising behaviours across development.

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