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Maternal high-fat diet has a negative impact on fertility—including an apparent direct effect on early development. In this issue, a new study connects this phenotype to depletion of Stella protein in oocytes, demonstrating environmental regulation of a maternal-effect gene.
This Perspective describes different study designs for the genetic analyses of large-scale cohorts, using Dutch cohorts as primary examples, and discusses lessons learned as well as recommendations for future cohort studies.
New genomic analyses indicate that pioneer transcription factors can sample a diverse repertoire of common binding sites among different cell types and become enriched where they cooperate with other factors specific to each cell. Pioneer-factor binding is mechanistically separate from, and is necessary for, subsequent phenomena of chromatin opening and epigenetic memory in vivo.
Two new studies identify rare homozygous variants in ADCY3 that are causal for monogenic obesity in consanguineous families of Pakistani origin and are associated with increased risk of obesity in Greenlandic individuals. Greenlandic carriers of homozygous loss-of-function variants in ADCY3, and individuals from trans-ancestry studies with a burden of rare ADCY3 loss-of-function variants, also have increased risk of type 2 diabetes.
Dysregulated lipid metabolism is a prominent feature of prostate cancers. Two papers in this issue identify novel genomic drivers of lipid metabolism in prostate cancer and provide implications for the subtyping and treatment of the disease.
