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Background:Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methods:A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Results:Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10−8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.Conclusions:We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Background: Pyloric stenosis is the most common condition requiring surgery in the first months of life. Case reports have suggested familial aggregation. However, to what extent this is caused by common environment or inheritance is unknown.Aims: To investigate familial aggregation of pyloric stenosis from monozygotic twins to fourth-generation relatives according to sex and maternal and paternal contributions and furthermore to estimate disease heritability.Methods: A population-based cohort study consisting of 1,999,738 children born in Denmark between 1977 and 2008. The cohort of children was followed for the first year of life during which 3362 children had surgery for pyloric stenosis.The familial aggregation of pyloric stenosis was evaluated by rate ratios of pyloric stenosis.Results: The incidence rate (per 1,000 person-years) of pyloric stenosis in the first year of life was 1.8 for singletons and 3.1 for twins. The rate ratios of pyloric stenosis were 182 (95% confidence interval [CI], 70.7-467) for monozygotic twins, 29.4 (95% CI, 9.45-91.5) for dizygotic twins, 18.5 (95% CI, 13.7-25.1) for siblings, 4.99 (95% CI, 2.59-9.65) for half-siblings, 3.06 (95% CI, 2.10-4.44) for cousins, and 1.60 (95% CI, 0.51-4.99) for half-cousins. We found no difference in the rate ratio for maternal and paternal relatives of a pyloric stenosis case and no difference according to own sex or sex of relative. The heritability of pyloric stenosis was 87%.Conclusion: Onset of pyloric stenosis in Danish children showed strong familial aggregation and heritability.