Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease

Stable carbon isotopes as potential sea-level indicators in salt marshes, North Carolina, USA

We compared the use of δ13C values and C:N ratios from salt-marsh sediments to reconstruct relative sea level (RSL) with an established approach using foraminifera. Analysis of bulk-organic sediment and plant samples collected along transects at two sites in North Carolina, USA demonstrates that sediment δ13C values can be used to distinguish between Spartina alterniflora-dominated low marsh (C photosynthetic pathway, δ13C values from —17.6‰ to 16.1‰) and Juncus roemerianus-dominated high marsh (C 3 photosynthetic pathway, δ13C values from —28.2‰ to —21.8‰) environments. Juncus roemerianus plants undergo little decompositional change in δ13C (average 0.8‰), although there is a clear difference between Spartina alterniflora tissue and bulk-organic sediments (approximately 4‰). C:N ratios on bulk-organic sediment from freshwater upland and salt-marsh environments converge during early diagenesis, rendering them of little use in reconstructing RSL. The utility of δ13C values as a sea-level indicator is limited by the elevational range of C4 plants, making it difficult to recognize salt-marsh subenvironments and improve the precision of RSL reconstructions. Furthermore, Juncus roemerianus-dominated high marsh and freshwater upland sediments cannot be adequately distinguished with δ13C values