Publications by authors named "Laurits Skov"

18 Publications

  • Page 1 of 1

Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry.

Nature 2021 Apr 7;592(7853):253-257. Epub 2021 Apr 7.

Francis Crick Institute, London, UK.

Modern humans appeared in Europe by at least 45,000 years ago, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania and Siberia who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common.
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http://dx.doi.org/10.1038/s41586-021-03335-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026394PMC
April 2021

Denisovan ancestry and population history of early East Asians.

Science 2020 10;370(6516):579-583

Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany.

We present analyses of the genome of a ~34,000-year-old hominin skull cap discovered in the Salkhit Valley in northeastern Mongolia. We show that this individual was a female member of a modern human population that, following the split between East and West Eurasians, experienced substantial gene flow from West Eurasians. Both she and a 40,000-year-old individual from Tianyuan outside Beijing carried genomic segments of Denisovan ancestry. These segments derive from the same Denisovan admixture event(s) that contributed to present-day mainland Asians but are distinct from the Denisovan DNA segments in present-day Papuans and Aboriginal Australians.
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http://dx.doi.org/10.1126/science.abc1166DOI Listing
October 2020

A high-coverage Neandertal genome from Chagyrskaya Cave.

Proc Natl Acad Sci U S A 2020 06 16;117(26):15132-15136. Epub 2020 Jun 16.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany;

We sequenced the genome of a Neandertal from Chagyrskaya Cave in the Altai Mountains, Russia, to 27-fold genomic coverage. We show that this Neandertal was a female and that she was more related to Neandertals in western Eurasia [Prüfer et al., Science 358, 655-658 (2017); Hajdinjak et al., Nature 555, 652-656 (2018)] than to Neandertals who lived earlier in Denisova Cave [Prüfer et al., Nature 505, 43-49 (2014)], which is located about 100 km away. About 12.9% of the Chagyrskaya genome is spanned by homozygous regions that are between 2.5 and 10 centiMorgans (cM) long. This is consistent with the fact that Siberian Neandertals lived in relatively isolated populations of less than 60 individuals. In contrast, a Neandertal from Europe, a Denisovan from the Altai Mountains, and ancient modern humans seem to have lived in populations of larger sizes. The availability of three Neandertal genomes of high quality allows a view of genetic features that were unique to Neandertals and that are likely to have been at high frequency among them. We find that genes highly expressed in the striatum in the basal ganglia of the brain carry more amino-acid-changing substitutions than genes expressed elsewhere in the brain, suggesting that the striatum may have evolved unique functions in Neandertals.
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http://dx.doi.org/10.1073/pnas.2004944117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334501PMC
June 2020

The nature of Neanderthal introgression revealed by 27,566 Icelandic genomes.

Nature 2020 06 22;582(7810):78-83. Epub 2020 Apr 22.

deCODE Genetics, Amgen, Reykjavik, Iceland.

Human evolutionary history is rich with the interbreeding of divergent populations. Most humans outside of Africa trace about 2% of their genomes to admixture from Neanderthals, which occurred 50-60 thousand years ago. Here we examine the effect of this event using 14.4 million putative archaic chromosome fragments that were detected in fully phased whole-genome sequences from 27,566 Icelanders, corresponding to a range of 56,388-112,709 unique archaic fragments that cover 38.0-48.2% of the callable genome. On the basis of the similarity with known archaic genomes, we assign 84.5% of fragments to an Altai or Vindija Neanderthal origin and 3.3% to Denisovan origin; 12.2% of fragments are of unknown origin. We find that Icelanders have more Denisovan-like fragments than expected through incomplete lineage sorting. This is best explained by Denisovan gene flow, either into ancestors of the introgressing Neanderthals or directly into humans. A within-individual, paired comparison of archaic fragments with syntenic non-archaic fragments revealed that, although the overall rate of mutation was similar in humans and Neanderthals during the 500 thousand years that their lineages were separate, there were differences in the relative frequencies of mutation types-perhaps due to different generation intervals for males and females. Finally, we assessed 271 phenotypes, report 5 associations driven by variants in archaic fragments and show that the majority of previously reported associations are better explained by non-archaic variants.
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http://dx.doi.org/10.1038/s41586-020-2225-9DOI Listing
June 2020

Detecting archaic introgression using an unadmixed outgroup.

PLoS Genet 2018 09 18;14(9):e1007641. Epub 2018 Sep 18.

Department of Genetics, University of Cambridge, Cambridge United Kingdom.

Human populations outside of Africa have experienced at least two bouts of introgression from archaic humans, from Neanderthals and Denisovans. In Papuans there is prior evidence of both these introgressions. Here we present a new approach to detect segments of individual genomes of archaic origin without using an archaic reference genome. The approach is based on a hidden Markov model that identifies genomic regions with a high density of single nucleotide variants (SNVs) not seen in unadmixed populations. We show using simulations that this provides a powerful approach to identifying segments of archaic introgression with a low rate of false detection, given data from a suitable outgroup population is available, without the archaic introgression but containing a majority of the variation that arose since initial separation from the archaic lineage. Furthermore our approach is able to infer admixture proportions and the times both of admixture and of initial divergence between the human and archaic populations. We apply the model to detect archaic introgression in 89 Papuans and show how the identified segments can be assigned to likely Neanderthal or Denisovan origin. We report more Denisovan admixture than previous studies and find a shift in size distribution of fragments of Neanderthal and Denisovan origin that is compatible with a difference in admixture time. Furthermore, we identify small amounts of Denisova ancestry in South East Asians and South Asians.
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http://dx.doi.org/10.1371/journal.pgen.1007641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161914PMC
September 2018

Dynamic Copy Number Evolution of X- and Y-Linked Ampliconic Genes in Human Populations.

Genetics 2018 07 16;209(3):907-920. Epub 2018 May 16.

Bioinformatic Research Center, Aarhus University, 8000, Denmark.

Ampliconic genes are multicopy, with the majority found on sex chromosomes and enriched for testis-expressed genes. While ampliconic genes have been associated with the emergence of hybrid incompatibilities, we know little about their copy number distribution and their turnover in human populations. Here, we explore the evolution of human X- and Y-linked ampliconic genes by investigating copy number variation (CNV) and coding variation between populations using the Simons Genome Diversity Project. We develop a method to assess CNVs using the read depth on modified X and Y chromosome targets containing only one repetition of each ampliconic gene. Our results reveal extensive standing variation in copy number both within and between human populations for several ampliconic genes. For the Y chromosome, we can infer multiple independent amplifications and losses of these gene copies even within closely related Y haplogroups, that diversified < 50,000 years ago. Moreover, X- and Y-linked ampliconic genes seem to have a faster amplification dynamic than autosomal multicopy genes. Looking at expression data from another study, we also find that X- and Y-linked ampliconic genes with extensive CNV are significantly more expressed than genes with no CNV during meiotic sex chromosome inactivation (for both X and Y) and postmeiotic sex chromosome repression (for the Y chromosome only). While we cannot rule out that the XY-linked ampliconic genes are evolving neutrally, this study gives insights into the distribution of copy number within human populations and demonstrates an extremely fast turnover in copy number of these regions.
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http://dx.doi.org/10.1534/genetics.118.300826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028258PMC
July 2018

Natural selection interacts with recombination to shape the evolution of hybrid genomes.

Science 2018 May 19;360(6389):656-660. Epub 2018 Apr 19.

Department of Biological Sciences, Columbia University, New York, NY, USA.

To investigate the consequences of hybridization between species, we studied three replicate hybrid populations that formed naturally between two swordtail fish species, estimating their fine-scale genetic map and inferring ancestry along the genomes of 690 individuals. In all three populations, ancestry from the "minor" parental species is more common in regions of high recombination and where there is linkage to fewer putative targets of selection. The same patterns are apparent in a reanalysis of human and archaic admixture. These results support models in which ancestry from the minor parental species is more likely to persist when rapidly uncoupled from alleles that are deleterious in hybrids. Our analyses further indicate that selection on swordtail hybrids stems predominantly from deleterious combinations of epistatically interacting alleles.
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http://dx.doi.org/10.1126/science.aar3684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069607PMC
May 2018

A high-coverage Neandertal genome from Vindija Cave in Croatia.

Science 2017 11 5;358(6363):655-658. Epub 2017 Oct 5.

Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

To date, the only Neandertal genome that has been sequenced to high quality is from an individual found in Southern Siberia. We sequenced the genome of a female Neandertal from ~50,000 years ago from Vindija Cave, Croatia, to ~30-fold genomic coverage. She carried 1.6 differences per 10,000 base pairs between the two copies of her genome, fewer than present-day humans, suggesting that Neandertal populations were of small size. Our analyses indicate that she was more closely related to the Neandertals that mixed with the ancestors of present-day humans living outside of sub-Saharan Africa than the previously sequenced Neandertal from Siberia, allowing 10 to 20% more Neandertal DNA to be identified in present-day humans, including variants involved in low-density lipoprotein cholesterol concentrations, schizophrenia, and other diseases.
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http://dx.doi.org/10.1126/science.aao1887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185897PMC
November 2017

Analysis of 62 hybrid assembled human Y chromosomes exposes rapid structural changes and high rates of gene conversion.

PLoS Genet 2017 Aug 28;13(8):e1006834. Epub 2017 Aug 28.

Bioinformatics Research Centre, Aarhus University, Aarhus C., Denmark.

The human Y-chromosome does not recombine across its male-specific part and is therefore an excellent marker of human migrations. It also plays an important role in male fertility. However, its evolution is difficult to fully understand because of repetitive sequences, inverted repeats and the potentially large role of gene conversion. Here we perform an evolutionary analysis of 62 Y-chromosomes of Danish descent sequenced using a wide range of library insert sizes and high coverage, thus allowing large regions of these chromosomes to be well assembled. These include 17 father-son pairs, which we use to validate variation calling. Using a recent method that can integrate variants based on both mapping and de novo assembly, we genotype 10898 SNVs and 2903 indels (max length of 27241 bp) in our sample and show by father-son concordance and experimental validation that the non-recurrent SNP and indel variation on the Y chromosome tree is called very accurately. This includes variation called in a 0.9 Mb centromeric heterochromatic region, which is by far the most variable in the Y chromosome. Among the variation is also longer sequence-stretches not present in the reference genome but shared with the chimpanzee Y chromosome. We analyzed 2.7 Mb of large inverted repeats (palindromes) for variation patterns among the two palindrome arms and identified 603 mutation and 416 gene conversions events. We find clear evidence for GC-biased gene conversion in the palindromes (and a balancing AT mutation bias), but irrespective of this, also a strong bias towards gene conversion towards the ancestral state, suggesting that palindromic gene conversion may alleviate Muller's ratchet. Finally, we also find a large number of large-scale gene duplications and deletions in the palindromic regions (at least 24) and find that such events can consist of complex combinations of simultaneous insertions and deletions of long stretches of the Y chromosome.
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http://dx.doi.org/10.1371/journal.pgen.1006834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591018PMC
August 2017

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference.

Nature 2017 08 26;548(7665):87-91. Epub 2017 Jul 26.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.
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http://dx.doi.org/10.1038/nature23264DOI Listing
August 2017

Comparison of three nudge interventions (priming, default option, and perceived variety) to promote vegetable consumption in a self-service buffet setting.

PLoS One 2017 31;12(5):e0176028. Epub 2017 May 31.

Department of Food Science, University of Copenhagen, Frederiksberg C, Denmark.

Background: Dietary choices in out-of-home eating are key for individual as well as for public health. These dietary choices are caused by a wide array of determinants, one of which is automatic decision-making. Nudging is attracting considerable interest due to its understanding and application of heuristic biases among consumers. The aim of this study is to test and compare three nudges in promoting vegetable consumption among test persons in a food lab-based experiment.

Methods: The initial sample consisted of 88 participants recruited in Copenhagen, Denmark. Each study participant was randomly assigned to one of the three experiments: priming, default and perceived variety. The priming arm of the experiment consisted of creating a leafy environment with green plants and an odour of herbs. In the default arm of the experiment, the salad was pre-portioned into a bowl containing 200g of vegetables. The third experiment divided the pre-mixed salad into each of its components, to increase the visual variety of vegetables, yet not providing an actual increase in items. Each individual was partaking twice thus serving as her/his own control, randomly assigned to start with control or experimental setting.

Results: The default experiment successfully increased the energy intake from vegetables among the study participants (124 kcal vs. 90 kcal in control, p<0.01). Both the priming condition and perceived variety reduced the total energy intake among the study participants (169 kcal, p<0.01 and 124 kcal, p<0.01, respectively), mainly through a decrease in the meat-based meal component.

Conclusions: Considerable progress has been made with regard to understanding the use of nudging in promoting a healthier meal composition, including increasing vegetable intake. This study suggests that the nature of a nudge-based intervention can have different effects, whether it is increasing intake of healthy components, or limiting intake of unhealthy meal components. This work has demonstrated that consumer behaviour can be influenced without restricting or providing incentives for behaviour change. The present findings have promising application to the foodservice sector.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176028PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450998PMC
September 2017

Perception of food consumed at home and dietary intake: A nationwide study from Brazil.

Appetite 2017 09 24;116:487-492. Epub 2017 May 24.

Department of Epidemiology, Institute of Social Medicine, Rio de Janeiro State University, Rua São Francisco Xavier, 524, 7° Andar, Bloco E, 20550-900, Rio de Janeiro, RJ, Brazil.

Perception of food consumed is a key factor in acknowledging the need for behavioral change to improve diet quality. We analyzed family dietary intake according to the head of household's perception of satisfaction with food consumed by the family. Households (n = 13,351) that participated in the Brazilian Household Budget Survey and the National Dietary Survey were classified as satisfied or dissatisfied with the food consumed in the home. We compared the family dietary intake of the two groups considering their socio-demographic characteristics. Satisfied families (n = 4429) reported statistically higher intake (in grams/1000 kcal) of vegetables (47.3 vs 33.7), fruits (46.9 vs 21.4), sugar-sweetened beverages (118 vs 71.7), milk and dairy (57.9 vs 34.6), and ultra-processed products (18.6 vs 9.8); and lower intake of rice (86.2 vs 112), beans (91.7 vs 136), and meat (76.5 vs 84.0) when compared to dissatisfied families (n = 1717). Among satisfied families, in the youngest group we found lower consumption of fruits and higher intake of sugar-sweetened beverages and ultra-processed products when compared to the oldest group. Also among satisfied families, those in the highest per capita income group presented higher intake of fruits and lower intake of beans than those in the lowest income group. Satisfied families in the highest income group also consumed more fruits and less beans than dissatisfied families in the same income group. Socio-demographic characteristics may influence perception of satisfaction with food consumed and potentially influence the success of public health efforts to offer nutrition guidance for families satisfied with diets that may or may not be comprised of healthy food and beverages.
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http://dx.doi.org/10.1016/j.appet.2017.05.036DOI Listing
September 2017

Making Healthy Choices Easier: Regulation versus Nudging.

Annu Rev Public Health 2016 30;37:237-51. Epub 2015 Dec 30.

Danish Nudging Network, 1208 København K, Denmark; email:

In recent years, the nudge approach to behavior change has emerged from the behavioral sciences to challenge the traditional use of regulation in public health strategies to address modifiable individual-level behaviors related to the rise of noncommunicable diseases and their treatment. However, integration and testing of the nudge approach as part of more comprehensive public health strategies aimed at making healthy choices easier are being threatened by inadequate understandings of its scientific character, its relationship with regulation, and its ethical implications. This article reviews this character and its ethical implication with a special emphasis on the compatibility of nudging with traditional regulation, special domains of experience, and the need for a more nuanced approach to the ethical debate. The aim is to advance readers' understanding and give guidance to those who have considered working with or incorporating the nudge approach into programs or policies aimed at making healthful choices easier.
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http://dx.doi.org/10.1146/annurev-publhealth-032315-021537DOI Listing
January 2017

Choice architecture interventions for increased vegetable intake and behaviour change in a school setting: a systematic review.

Perspect Public Health 2016 May 11;136(3):132-42. Epub 2015 Aug 11.

Department of Food Science, University of Copenhagen, Denmark.

Aims: The primary objective of this review is to assess the prevalence and quality of published studies on the effect of choice architectural nudge interventions promoting vegetable consumption among adolescents. Additionally, this review aims to identify studies estimating adolescents' attitude towards choice architectural nudge interventions.

Methods: Web of Science, Scopus and PubMed were searched systematically for experimental studies with a predefined search strategy in the period November-December 2013. Publications were included following predetermined inclusion criteria. Studies were evaluated as of high, moderate or weak quality. Finally, studies were grouped by the type of intervention and underwent a narrative synthesis.

Results: The search showed that only very few studies investigated the effects of choice architectural nudging interventions on vegetable consumption, and none of them had attitude towards behavioural interventions as an outcome measure. Twelve studies met the inclusion criteria. The results of the 12 studies were inconclusive, and the majority of studies were of weak or moderate quality.

Conclusion: This review uncovers a gap in knowledge on the effect of choice architectural nudge interventions aiming to promote the intake of vegetables among adolescents in a school context. It also highlights that no previous studies have considered the attitudes towards choice architectural nudge interventions as a potential factor for their success - or lack thereof - in achieving the desired goal of increased vegetable consumption.
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http://dx.doi.org/10.1177/1757913915596017DOI Listing
May 2016

Inference of purifying and positive selection in three subspecies of chimpanzees (Pan troglodytes) from exome sequencing.

Genome Biol Evol 2015 Mar 30;7(4):1122-32. Epub 2015 Mar 30.

Bioinformatics Research Centre, Aarhus University, Denmark

We study genome-wide nucleotide diversity in three subspecies of extant chimpanzees using exome capture. After strict filtering, Single Nucleotide Polymorphisms and indels were called and genotyped for greater than 50% of exons at a mean coverage of 35× per individual. Central chimpanzees (Pan troglodytes troglodytes) are the most polymorphic (nucleotide diversity, θw = 0.0023 per site) followed by Eastern (P. t. schweinfurthii) chimpanzees (θw = 0.0016) and Western (P. t. verus) chimpanzees (θw = 0.0008). A demographic scenario of divergence without gene flow fits the patterns of autosomal synonymous nucleotide diversity well except for a signal of recent gene flow from Western into Eastern chimpanzees. The striking contrast in X-linked versus autosomal polymorphism and divergence previously reported in Central chimpanzees is also found in Eastern and Western chimpanzees. We show that the direction of selection statistic exhibits a strong nonmonotonic relationship with the strength of purifying selection S, making it inappropriate for estimating S. We instead use counts in synonymous versus nonsynonymous frequency classes to infer the distribution of S coefficients acting on nonsynonymous mutations in each subspecies. The strength of purifying selection we infer is congruent with the differences in effective sizes of each subspecies: Central chimpanzees are undergoing the strongest purifying selection followed by Eastern and Western chimpanzees. Coding indels show stronger selection against indels changing the reading frame than observed in human populations.
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http://dx.doi.org/10.1093/gbe/evv058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419804PMC
March 2015

A systematic review of types of healthy eating interventions in preschools.

Nutr J 2014 Jun 6;13:56. Epub 2014 Jun 6.

Development of Planning and Development, Research group for Meal science and Public Health Nutrition - MENU, University of Aalborg, A,C, Meyers Vaenge 15, Copenhagen SV 2450, Denmark.

Background: With the worldwide levels of obesity new venues for promotion of healthy eating habits are necessary. Considering children's eating habits are founded during their preschool years early educational establishments are a promising place for making health promoting interventions.

Methods: This systematic review evaluates different types of healthy eating interventions attempting to prevent obesity among 3 to 6 year-olds in preschools, kindergartens and day care facilities. Studies that included single interventions, educational interventions and/or multicomponent interventions were eligible for review. Included studies also had to have conducted both baseline and follow-up measurements.A systematic search of the databases Scopus, Web of Science, CINAHL and PubMed was conducted to identify articles that met the inclusion criteria. The bibliographies of identified articles were also searched for relevant articles.

Results: The review identified 4186 articles, of which 26 studies met the inclusion criteria. Fifteen of the interventions took place in preschools, 10 in kindergartens and 1 in another facility where children were cared for by individuals other than their parents. Seventeen of the 26 included studies were located in North America, 1 in South America, 5 in Asia, and 3 in a European context.Healthy eating interventions in day care facilities increased fruit and vegetable consumption and nutrition related knowledge among the target groups. Only 2 studies reported a significant decrease in body mass index.

Conclusions: This review highlights the scarcity of properly designed healthy eating interventions using clear indicators and verifiable outcomes. The potential of preschools as a potential setting for influencing children's food choice at an early age should be more widely recognised and utilised.
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http://dx.doi.org/10.1186/1475-2891-13-56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074866PMC
June 2014