Twin studies advance the understanding of gene–environment interplay in human nutrigenomics

Pallister, Tess; Spector, Tim D.; Menni, Cristina

doi:10.1017/s095442241400016x

Cited by 15 publications

(9 citation statements)

References 97 publications

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“…Like VFM, 54 we found this score to be strongly determined by genetics ( h 2 : 44%), which agrees with previous findings where the heritability of ‘unhealthy’ diet patterns ranged from 33 to 50%. 55 The limitations of our study also warrant discussion. First, our population was predominantly female and therefore, our results may not apply to men.…”

Section: Discussionmentioning

confidence: 85%

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling

et al. 2017

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Background/Objectives:Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence visceral fat (VF) development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM.Subjects/Methods:In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the ‘VFM diet score’ in the remainder of the sample. Using linear regression (adjusted for covariates, including body mass index and total fat mass), we investigated associations between the VFM diet score, the blood metabolomics profile and the fecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (⩾1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence.Results:Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (beta (s.e.): 0.281 (0.091); P=0.002), butyrylcarnitine (0.199 (0.087); P=0.023) and hippurate (−0.297 (0.095); P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042 (0.011), P=8.47 × 10−5), VFM (0.057 (0.019), P=2.73 × 10−3) and hippurate (−0.075 (0.032), P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016 (0.004), P=9.82x10−6).Conclusions:We linked a dietary VFM score and VFM to E. dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM.

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Section: Discussionmentioning

confidence: 85%

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling

et al. 2017

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“…Accounting for these confounding genetic effects and additionally many shared environmental and cohort effects provides significantly greater power than other study designs (Rakyan et al, 2011), and these combined numbers across the consortium will enable rigorous replication of small scale positive findings, as well as novel discoveries to be made. Many other omics technologies may be applied to disease discordant twins (metabolomics, transcriptomics, glycomics, metagenomics, proteomics), providing a complete picture of the processes involved in disease development and progression (Pallister et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium

et al. 2015

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Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

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“…Findings from twin studies have indicated that genetics plays a major role in several diet-related phenotypes including energy and macronutrient intakes, dietary patterns, and the intake of specific foods [28]. Twins provide a naturally unique case-control experiment whereas the classical twin design compares the similarity of identical/monozygotic (MZ) and dizygotic (DZ) twins.…”

Section: Introductionmentioning

confidence: 99%

Heritability of the timing of food intake

et al. 2019

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Twin studies advance the understanding of gene–environment interplay in human nutrigenomics

Cited by 15 publications

References 97 publications

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium

Heritability of the timing of food intake

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