Twin studies have been used for decades to estimate the relative importance of genes and environments for traits, behaviors and disorders. A very large meta-analysis of all twin studies conducted during the past 50 years (almost 3000 publications) revealed that across all studied traits the average reported heritability was 49%, meaning that about 50% of the variation in traits is due to genetic factors (1).

1. Methods and theory of classical twin design

By comparing the differences and similarities between twins, researchers use them as a natural experiment to study whether a trait, phenotype or disease is due to nature (genetic predisposition) or nurture (environmental factors).

In order to get a better understanding of twin studies, one must first understand the two types of twins:

  • Monozygotic (MZ) or identical twins were conceived in a single egg, which split and forms two embryos. Therefore, MZ twins share all their genes (100%), and are definitely the same sex.
  • Dizygotic (DZ) or fraternal twins were developing from a separate egg and each egg is fertilized by its own sperm cell, and therefore sharing on average 50% of their genes. DZ twins could be of the same sex or different sex.

Based on the different degree of genetic and the similar extent of prenatal and later environmental factors sharing between MZ and DZ twins, MZ twin pairs may show a higher similarity on a given trait, as compared with DZ twins, if genes significantly influence that trait. On the other hand, if MZ and DZ twin pairs share a trait to an equal extent, it is likely that the environment influences the trait more than genetic factors.

The similarity for a given trait is estimates via intra-class correlations (ICC), and similarity across different traits by the cross-twin cross-trait correlations (CTCT). Comparison of correlations across MZ and DZ pairs allows for the variance (V) of a given trait to be decomposed into three factors:

  • Genetic factors, including additive genetic factors (A), and dominant genetic factors (D)
  • Shared environmental factors (C), that is events that happen to both twins, affecting them in the same way. For example, the socio-economic status of the family, the general personality and general parenting styles and beliefs of the parents.
  • Non-shared or unique environmental factors (E), that is events happen to one twin but not the other one, or the events affect either twin in a different way. For example, school and classroom environment, also including measurement error.

Under then assumptions of no interaction and no covariance between A, C, D, and E, the total variance of a phenotype (P) can be expressed as:


Narrow sense heritability is defined as the proportion of variance in a trait due to additive genetic effects (A):


Broad sense heritability as the proportion of variance due to additive and dominance genetic effects (A+D):


The classical twin model can be extended to explore bivariate and multivariate traits association, and test for differences between males and females by using sex-limitation models. More information on how to conduct classical and advanced twin model fitting analyses, please refer to (2) and (3).

2. Important advantages of twin studies

  • Estimate the relative importance of genetic factors (i.e., heritability) of one or more traits
  • Help identify shared genetic factors that influence different traits, behaviors and disorders.
  • Explore the causal status of environmental risk factors by controlling for genetic and shared environmental confounding.
  • Offers unique opportunities to study the gene-environmental interplay, including both gene-environmental correlations and gene-environmental interactions.

In summary, the twin study design is considered an important behavioral genetic approach that has been used in many fields, including biology, psychology and sociology. Using a substantial amount of the published twin research (and other genetic informative studies, e.g. sibling comparison, adoption studies), Plomin et al. summarized the top 10 replicated and important findings (4). These findings included:

  • All psychological traits show significant and substantial genetic influence;
  • No traits are 100% heritable, highlighting the importance of environmental factors, and
  • The heritability is caused by many genes of small effect.

Most of these findings or discoveries that could only have been found using genetically sensitive research designs.

In the Eat2BeNice project, we are currently using data from Swedish Twin Register ( to estimate the heritability of unhealthy eating habits and ADHD symptoms in adults, and also to investigate the relative importance of genetic, shared environmental and non-shared environmental factors for the overlap between adult ADHD symptoms and different dietary habits diets. We will also test specific hypothesis regarding gene-environmental interactions.

Lin Li, MSc, PhD student in the School of Medical Science, Örebro University, Sweden.

Henrik Larsson, PhD, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.


  1. Polderman TJ, Benyamin B, de Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature genetics. 2015;47(7):702-9.
  2. Neale, M. C. and Meas, H. M. Methodology for genetic studies of twins and families. and the paper Rijsdijk FV & Sham PC. (2002),
  3. Analytic Approaches to Twin Data using Structural Equation Models. Briefings in Bioinformatics, 3 (2), 119 -133.
  4. Plomin, Robert, et al. “Top 10 replicated findings from behavioral genetics.” Perspectives on psychological science11.1 (2016): 3-23.


Please share and like us:

In our Eat2BeNice project, we want to know how lifestyle-factors, and nutrition contribute to impulsive, compulsive, and externalizing behaviours. The best way to investigate this is to follow lifestyle and health changes in individuals for a longer period of time. This is called a prospective cohort study, as it allows us to investigate whether lifestyle and nutrition events at one point in time are associated with health effects at a later point.

Luckily we can make use of the LifeGene project for this. LifeGene is a unique project that aims to advance the knowledge about how genes, environments, and lifestyle-factors affect our health. Starting from September 2009, individuals aged 18 to 45 years, were randomly sampled from the Swedish general population. Participants were invited to include their families (partner and children). All study participants will be prompted annually to respond to an update web-based questionnaire on changes in household composition, symptoms, injuries and pregnancy.

The LifeGene project (1) consists of two parts: First, a comprehensive web-based questionnaire to collect information about the physical, mental and social well-being of the study participants. Nine themes are provided for adults: Lifestyle (including detailed dietary intake and nutrition information), Self-care, Woman’s health, Living habits, Healthy history, Asthma and allergy, Injuries, Mental health and Sociodemographic. The partners and children receive questions about two to four of these themes. For children below the age of 15 the parents are requested to answer the questions for them.

The second part is a health test: at the test centres, the study participants are examined for weight, height, waist, hip and chest circumference, heart rate and blood pressure, along with hearing. Blood and urine samples are also taken at the test centres for analysis and bio-banking.

Up until 2019, LifeGene contains information from a total of 52,107 participants. Blood, serum and urine from more than 29,500 participants are stored in Karolinska Institute (KI) biobank. From these we can analyze genetic data and biomarkers for diabetes, heart disease, kidney disease and other somatic diseases. Based on LifeGene, we aim to identify nutritional and lifestyle components that have the most harmful or protective effects on impulsive, compulsive, and externalizing behaviors across the lifespan, and further examine whether nutritional factors are important mediators to link impulsivity, compulsivity and metabolic diseases(e.g. obesity, diabetes). We will update you on our results in the near future.

For more information, please go to the LifeGene homepage LifeGene is an open-access resource for many national and international researchers and a platform for a myriad of biomedical research projects. Several research projects are underway at LifeGene

This was co-authored by Henrik Larsson, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.

Lin Li, MSc, PhD student in the School of Medical Science, Örebro University, Sweden.

Henrik Larsson, PhD, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.


  1. Almqvist C, Adami HO, Franks PW, Groop L, Ingelsson E, Kere J, et al. LifeGene–a large prospective population-based study of global relevance. Eur J Epidemiol. 2011;26(1):67-77.
Please share and like us:

We have discussed the association between ADHD and obesity in our first blog (, briefly summarized, evidence from various study designs suggested that shared etiological factors might contribute to the above association. Recently, a large genome-wide association study (GWAS) on risk genes for ADHD reported a significant genetic correlation between ADHD and a higher risk of overweight and obesity, increased BMI, and higher waist-to-hip ratio, which further supported that there could be genetic overlap between obesity and ADHD (1).

Considering the previously described occurrence of unhealthy dietary intake in children and adolescents with ADHD in our second blog (, along with the fact that bad eating behaviours are crucial factors for the development of obesity, We can speculate that the shared genetic effects between ADHD and unhealthy dietary intake may also explain the potential bidirectional diet-ADHD associations. Is there any available evidence to support the above hypothesis?

To date, dopaminergic dysfunctions underpinning reward deficiency processing (or neural reward anticipation), was reported as a potential shared biological mechanism, through which the genetic variants could increase both the risk for ADHD and unhealthy dietary intake or obesity. Via the Gut-Brain axis, a two-way and high-speed connection, the gut can talk to the brain directly. According to the study (2), a higher proportion of bacteria that produce a substance that can be converted into dopamine was found in the intestines of people with ADHD than those without ADHD. Using functional magnetic resonance imaging (fMRI), they further found that the participants with more of these bacteria in their intestines displayed less activity in the reward sections of the brain, which constitutes one of the hallmarks of ADHD. We are therefore proposing the idea that there could be a biological pathway- ‘dietary habits-gut (microorganism)-reward system (dopamine)-ADHD’, through which the shared genetic effects between ADHD and unhealthy dietary intake may play a role.

In order to determine whether the genetic overlap between ADHD and dietary habits actually exists, we will in our next Eat2beNice project use twin methodology and unique data from the Swedish Twin Register. We will keep you updated!

This was co-authored by Henrik Larsson, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.

Lin Li, MSc, PhD student in the School of Medical Science, Örebro University, Sweden.

Henrik Larsson, PhD, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.

1. Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature genetics. 2019;51(1):63.

2. Aarts E, Ederveen TH, Naaijen J, Zwiers MP, Boekhorst J, Timmerman HM, et al. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One. 2017;12(9):e0183509.

Please share and like us:

Recent research (1,2) on children and adolescents has reported that elevated levels of ADHD symptoms are positively associated with unhealthy dietary habits, including a higher consumption of refined sugars, processed food, soft drink, instant noodles, and a lower intake of vegetables and fruits. However, the link between low-quality diets and risk of ADHD in adults is still not well established, which would be further explored in the ongoing Eat2beNICE research project.

What is the underlying mechanism for an association between ADHD and unhealthy dietary habits? There is still no clear answer. Nemours’ potential biological pathways, by which dietary intake could have an impact on mental health, has been proposed in the literature (2). For example, iron and zinc are cofactors for dopamine and norepinephrine production (essential factors in the etiology of ADHD), so unbalanced diet with lower levels of iron and zinc may further contribute to the development of ADHD. However, we cannot overlook the possibility of a bi-directional relationship between diet quality and ADHD, especially when the interest in the concept of “food addiction” has received increased attention.

Food addiction refers to being addicted to certain foods (e.g. highly processed foods, highly palatable foods, sweet and junk foods) in a similar way as drug addicts are addicted to drugs. Animal models (3) have suggested that highly processed foods may possess addictive properties. Rats given high-sugar or high-fat foods display symptoms of binge eating, such as consuming increased quantities of food in short time periods, and seeking out highly processed foods despite negative consequences (e.g. electric foot shocks). One human study (4) found that individuals with high levels of ADHD-like traits (e.g. high levels of impulsively, disorganised, attention problems) were more likely to suffer from problematic eating behaviour with overconsumption of specific highly palatable foods in an addiction-like manner. Therefore, food addiction may, just as substance abuse, be over-represented among individuals with ADHD.

Thus, it seems there could be a vicious cycle between unhealthy dietary habits and ADHD: ADHD may lead to a worse choice of diet, lowering the health quality, which could eventually exacerbate ADHD symptoms. We will further test the bidirectional diet-ADHD associations in the ongoing Eat2beNice project.

This was co-authored by Henrik Larsson, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.

Lin Li, MSc, PhD student in the School of Medical Science, Örebro University, Sweden.
Henrik Larsson, PhD, professor in the School of Medical Science, Örebro University and Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden.

1. Kim KM, Lim MH, Kwon HJ, Yoo SJ, Kim EJ, Kim JW, et al. Associations between attention-deficit/hyperactivity disorder symptoms and dietary habits in elementary school children. Appetite. 2018;127:274-9.

2. Rios-Hernandez A, Alda JA, Farran-Codina A, Ferreira-Garcia E, Izquierdo-Pulido M. The Mediterranean Diet and ADHD in Children and Adolescents. Pediatrics. 2017;139(2).

3. Gearhardt AN, White MA, Potenza MN. Binge Eating Disorder and Food Addiction. Curr Drug Abuse Rev. 2011;4(3):201-7.

4. Ptacek R, Stefano GB, Weissenberger S, Akotia D, Raboch J, Papezova H, et al. Attention deficit hyperactivity disorder and disordered eating behaviors: links, risks, and challenges faced. Neuropsychiatr Dis Treat. 2016;12:571-9.

Please share and like us:

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopment disorder characterized by inattention or hyperactivity–impulsivity, or both. It might seem paradoxical, but many studies indicate that individuals with a diagnosis of ADHD suffer from overweight and obesity. Therefore, it is important to understand the underlying mechanism that put individuals with ADHD at risk for obesity.

 Evidence from within-individual study
A systematic review and meta-analysis (1) based on 728,136 individuals from 42 studies, suggested a significant association between ADHD and obesity both in children/adolescents and adults. The pooled prevalence of obesity was increased by about 70% in adults with ADHD and 40% in children with ADHD compared with individuals without ADHD. However, due to the lack of longitudinal and genetically-informative studies, the meta-analysis was unable to explain the exact direction of association and the underlying etiologic mechanisms. There are several potential explanations:

  • ADHD causing obesity: The impulsivity and inattention components of ADHD might lead to disordered eating patterns and poor planning lifestyles, and further caused weight gain.
  • Obesity causing ADHD: Factors associated with obesity, for example dietary intake, might lead to ADHD-like symptoms through the microbiota-gut-brain axis.
  • ADHD and obesity may share etiological factors: ADHD and obesity may share dopaminergic dysfunctions underpinning reward deficiency processing. So the same biological mechanism may lead to both ADHD and obesity. This is difficult to investigate within individuals, but family studies can help to test this hypothesis.

We will further investigate these possibilities in the Eat2beNICE research project by using both perspective cohort study and twin studies.

Evidence from a recent within-family study
Recently, a population-based familial co-aggregation study in Sweden (2) was conducted to explore the role of shared familial risk factors (e.g. genetic variants, family disease history) in the association between ADHD and obesity. They identified 523,237 full siblings born during 1973–2002 for the 472,735 index males in Sweden, and followed them until December 3, 2009. The results suggest that having a sibling with overweight/obesity is a risk factor for ADHD. This makes it likely that biological factors (that are shared between family members) increase the risk for both ADHD and obesity.

Evidence from across-generation study
Given that both ADHD and obesity are highly heritable complex conditions, across-generation studies may also advance the understanding of the link between ADHD and obesity.

A population-based cohort study (3) based on a Swedish nationwide sample of 673,632individuals born during 1992-2004, was performed to explore the association between maternal pre-pregnancy obesity and risk of ADHD in offspring. The sibling-comparison study design was used to test the role of shared familial factors for the potential association. The results suggest that the association between maternal pre-pregnancy obesity and risk of ADHD in offspring might be largely explained by shared familial factors, for example, genetic factors transmitted from mother to child that contribute to both maternal pre-pregnancy obesity and ADHD.

Together, based on previous evidence from various study designs, there is evidence to suggest that the association between ADHD and obesity mainly is caused by shared etiological factors. However, future studies on different population are still needed to further test these findings.

1. Cortese S, Moreira-Maia CR, St Fleur D, Morcillo-Penalver C, Rohde LA, Faraone SV. Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis. The American journal of psychiatry. 2016;173(1):34-43.

2. Chen Q, Kuja-Halkola R, Sjolander A, Serlachius E, Cortese S, Faraone SV, et al. Shared familial risk factors between attention-deficit/hyperactivity disorder and overweight/obesity – a population-based familial coaggregation study in Sweden. J Child Psychol Psychiatry. 2017;58(6):711-8.

3. Chen Q, Sjolander A, Langstrom N, Rodriguez A, Serlachius E, D’Onofrio BM, et al. Maternal pre-pregnancy body mass index and offspring attention deficit hyperactivity disorder: a population-based cohort study using a sibling-comparison design. Int J Epidemiol. 2014;43(1):83-90.

Please share and like us:

Welcome to New Brain Nutrition. You can enjoy FREE Online Courses when you Log In or Join here.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 728018

New Brain Nutrition is a project and brand of Eat2BeNice, a consortium of 18 European University Hospitals throughout the continent.

You may log in here to our Intranet website with your authorized user name and password.