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Paternal grandfather's access to food predicts all-cause and cancer mortality in grandsons.

ABSTRACT: Studies of animals and plants suggest that nutritional conditions in one generation may affect phenotypic characteristics in subsequent generations. A small number of human studies claim to show that pre-pubertal nutritional experience trigger a sex-specific transgenerational response along the male line. A single historical dataset, the Överkalix cohorts in northern Sweden, is often quoted as evidence. To test this hypothesis on an almost 40 times larger dataset we collect harvest data during the pre-pubertal period of grandparents (G0, n?=?9,039) to examine its potential association with mortality in children (G1, n?=?7,280) and grandchildren (G2, n?=?11,561) in the Uppsala Multigeneration Study. We find support for the main Överkalix finding: paternal grandfather's food access in pre-puberty predicts his male, but not female, grandchildren's all-cause mortality. In our study, cancer mortality contributes strongly to this pattern. We are unable to reproduce previous results for diabetes and cardiovascular mortality.

SUBMITTER: Vagero D

PROVIDER: S-EPMC6290014 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Paternal grandfather's access to food predicts all-cause and cancer mortality in grandsons.

Vågerö Denny D Pinger Pia R PR Aronsson Vanda V van den Berg Gerard J GJ

Nature communications 20181211 1

Studies of animals and plants suggest that nutritional conditions in one generation may affect phenotypic characteristics in subsequent generations. A small number of human studies claim to show that pre-pubertal nutritional experience trigger a sex-specific transgenerational response along the male line. A single historical dataset, the Överkalix cohorts in northern Sweden, is often quoted as evidence. To test this hypothesis on an almost 40 times larger dataset we collect harvest data during t ...[more]

PMID: 30538239

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Project description:BackgroundCoronary artery disease (CAD) is influenced by genetic variation and traditional risk factors. Polygenic risk scores (PRS), which can be ascertained before the development of traditional risk factors, have been shown to identify individuals at elevated risk of CAD. Here, we demonstrate that a genome-wide PRS for CAD predicts all-cause mortality after accounting for not only traditional cardiovascular risk factors but also angiographic CAD itself.MethodsIndividuals who underwent coronary angiography and were enrolled in an institutional biobank were included; those with prior myocardial infarction or heart transplant were excluded. Using a pruning-and-thresholding approach, a genome-wide PRS comprised of 139 239 variants was calculated for 1503 participants who underwent coronary angiography and genotyping. Individuals were categorized into high PRS (hiPRS) and low-PRS control groups using the maximally selected rank statistic. Stratified analysis based on angiographic findings was also performed. The primary outcome was all-cause mortality following the index coronary angiogram.ResultsIndividuals with hiPRS were younger than controls (66 years versus 69 years; P=2.1×10-5) but did not differ by sex, body mass index, or traditional risk-factor profiles. Individuals with hiPRS were at significantly increased risk of all-cause mortality after cardiac catheterization, adjusting for traditional risk factors and angiographic extent of CAD (hazard ratio, 1.6; 95% CI, 1.2-2.2; P=0.004). The strongest increase in risk of all-cause mortality conferred by hiPRS was seen among individuals without angiographic CAD (hazard ratio, 2.4; 95% CI, 1.1-5.5; P=0.04). In the overall cohort, adding hiPRS to traditional risk assessment improved prediction of 5-year all-cause mortality (area under the receiver-operating curve 0.70; 95% CI, 0.66-0.75 versus 0.66; 95% CI, 0.61-0.70; P=0.001).ConclusionsA genome-wide PRS improves risk stratification when added to traditional risk factors and coronary angiography. Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality.

Dataset Information

Paternal grandfather's access to food predicts all-cause and cancer mortality in grandsons.

Publications

Paternal grandfather's access to food predicts all-cause and cancer mortality in grandsons.

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