Gene-by-environment experiments: a new approach to finding the missing heritability

IJzendoorn, Marinus H. van; Bakermans‐Kranenburg, Marian J.; Belsky, Jay; Beach, Steven R. H.; Brody, Gene H.; Dodge, Kenneth A.; Greenberg, Mark T.; Posner, Michael I.; Scott, Stephen

doi:10.1038/nrg2764-c1

Cited by 107 publications

(70 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increasingly, experimental designs are considering gene-environment interactions to account for the ''missing heritability'' associated with complex phenotypes like obesity (Van IJzendoorn et al 2011). Given the established contribution of n-3 PUFAs to changes in adiposity phenotypes and the availability of a precise biomarker for n-3 PUFA intake (d 15 N) in Yup'ik people (O'Brien et al 2009), we tested whether individuals SNPs and the GRS associations with adiposity phenotypes were modified by consumption of n-3 PUFA.…”

Section: Discussionmentioning

confidence: 99%

“…Increasingly, gene-by-environment interactions have been suggested to account for the ''missing heritability'' in complex traits (Van IJzendoorn et al 2011). Genetic association studies that recruit isolated populations, characterized by an environment that is less heterogeneous and reduced genetic admixture, may have a unique opportunity to delineate genetic and environmental factors that impact the heritable component of obesity (Heutink and Oostra 2002).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup’ik people

et al. 2013

View full text Add to dashboard Cite

n-3 Polyunsaturated fatty acids (n-3 PUFAs) have anti-obesity effects that may modulate risk of obesity, in part, through interactions with genetic factors. Genomewide association studies (GWAS) have identified genetic variants associated with body mass index (BMI); however, the extent to which these variants influence adiposity through interactions with n-3 PUFAs remains unknown. We evaluated 10 highly replicated obesity GWAS single nucleotide polymorphisms (SNPs) for individual and cumulative associations with adiposity phenotypes in a cross-sectional sample of Yup'ik people (n = 1,073) and evaluated whether genetic associations with obesity were modulated by n-3 PUFA intake. A genetic risk score (GRS) was calculated by adding the BMI-increasing alleles across all 10 SNPs. Dietary intake of n-3 PUFAs was estimated using nitrogen stable isotope ratio (d 15 N) of red blood cells, and genotype-phenotype analyses were tested in linear models accounting for familial correlations. GRS was positively associated with BMI (p = 0.012), PBF (p = 0.022), ThC (p = 0.025), and waist circumference (p = 0.038). The variance in adiposity phenotypes explained by the GRS included BMI (0.7 %), PBF (0.3 %), ThC (0.7 %), and WC (0.5 %). GRS interactions with n-3 PUFAs modified the association with adiposity and accounted for more than twice the phenotypic variation (*1-2 %), relative to GRS Electronic supplementary material The online version of this article

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup’ik people

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In an effort to overcome these methodological shortcomings, researchers have taken advantage of intervention/prevention trials, wherein both randomization and environmental manipulation are inherent. The goal of this groundbreaking work appears to be focused on better elucidating the etiology of psychopathology, finding missing heritability, and describing ES phenomena more generally, rather than on directly translating such findings into more tailored, clinical approaches [31][32][33][34][35][36]. Our prevention framework proposes to advance this experimental work one step further, a translational step, with an eye toward personalized, precision-based prevention.…”

Section: Experimental Evidence Of Esmentioning

confidence: 99%

Application of environmental sensitivity theories in personalized prevention for youth substance abuse: a transdisciplinary translational perspective

Thibodeau

August

Cicchetti

et al. 2015

Behav. Med. Pract. Policy Res.

View full text Add to dashboard Cite

Preventive interventions that target high-risk youth, via one-size-fits-all approaches, have demonstrated modest effects in reducing rates of substance use. Recently, substance use researchers have recommended personalized intervention strategies. Central to these approaches is matching preventatives to characteristics of an individual that have been shown to predict outcomes. One compelling body of literature on person × environment interactions is that of environmental sensitivity theories, including differential susceptibility theory and vantage sensitivity. Recent experimental evidence has demonstrated that environmental sensitivity (ES) factors moderate substance abuse outcomes. We propose that ES factors may augment current personalization strategies such as matching based on risk factors/severity of problem behaviors (risk severity (RS)). Specifically, individuals most sensitive to environmental influence may be those most responsive to intervention in general and thus need only a brief-type or lower-intensity program to show gains, while those least sensitive may require more comprehensive or intensive programming for optimal responsiveness. We provide an example from ongoing research to illustrate how ES factors can be incorporated into prevention trials aimed at high-risk adolescents. Keywords Substance use, Prevention, Environmental sensitivity, R i s k s e v e r i t y, D i ff e r e n t i a l s u s c e p t i b i l i t y, PersonalizationAlcohol and other drug use among adolescents is a serious public health concern in the USA. For example, by late adolescence, over 78 % of teens will have experimented with alcohol, over 47 % will be engaged in regular drinking habits, and over 14 % will have met criteria for lifetime abuse [1]. Despite herculean efforts over the previous five decades to stem the rising tide of substance use, treatment approaches (largely based on behavioral parent training and cognitive behavioral therapy principles) have been modest at best; there is considerable variability in outcomes, and no one model works similarly for all youth [2]. Even among those who experience initial success following treatment, relapse rates are high [3].

show abstract

“…Thus, tests of interaction must take this phenomenon into account. Gene-environment correlation may be circumvented in a randomized control trial because the randomization breaks any potential gene-environment correlation (van IJzendoorn et al 2011). In addition, tests of gene-environment-interaction must consider the fact that the power to detect interactions is often lower than power to detect main effects (Duncan and Keller 2011).…”

Section: Statistical Tests Of Gene-environment Interactionmentioning

confidence: 99%

Editorial Policy for Candidate Gene Studies

Johnston

Lahey

Matthys

2013

J Abnorm Child Psychol

View full text Add to dashboard Cite

Gene-by-environment experiments: a new approach to finding the missing heritability

Cited by 107 publications

References 13 publications

Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup’ik people

Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup’ik people

Application of environmental sensitivity theories in personalized prevention for youth substance abuse: a transdisciplinary translational perspective

Editorial Policy for Candidate Gene Studies

Contact Info

Product

Resources

About