BY: Melissa Munn-Chernoff, PhD

DATE: November 6, 2015

As a twin researcher, I often get asked what the value of twin research is nowadays, since advances in molecular genetic research are allowing us to identify precise genes that contribute to genetically influenced traits. In the past, twin studies were the primary way that we identified whether traits were influenced by genes. Briefly, a classical twin study compares the resemblance of identical and fraternal twins for a trait or disorder. Identical twins share 100% of their genetic make-up, whereas fraternal twins share, on average, 50% of their genetic make-up, making them no more alike than ordinary biological siblings. A recent report¹ that combined twin samples examining nearly 17,000 traits from the past 50 years showed just how important genetic factors are for psychiatric disorders, medical conditions, and various other traits. Separate twin studies have demonstrated that anorexia nervosa, bulimia nervosa, binge-eating disorder,² and purging disorder³ are influenced by genetic factors. Thinking of other ways to include twins in research, beyond showing that there is genetic risk for traits, will be important steps forward in our understanding of psychiatric disorders. Here are some additional ways researchers are including twins to understand psychiatric disorders (for additional information, please see review by van Dongen and colleagues)⁴:

1. Understanding how genetic and environmental risk work together without collecting genetic material (or DNA). Twin registries around the world have collected information not only about psychiatric disorders, but also about environmental experiences (e.g., stressful life events, education, and peer influences). Some of these twin samples can even be linked with national registries to provide additional information on environmental factors. Without having to collect DNA, twin studies can determine how certain environmental factors effect genetic risk for traits. For example, Suisman and colleagues⁵ reported an increased genetic risk for body dissatisfaction among women from divorced families.

2. Co-twins act as a perfect case-control design. By examining differences on an outcome (e.g., binge eating) in twins within the same twin pair who differ in their experience for an exposure (e.g., early alcohol use), we can investigate whether after accounting for familial risk (i.e., genetic and shared environmental effects), there is still an association between two traits. Co-twins from the same twin pair serve as perfect controls for each other because they shared the same prenatal environment and are matched for age and sex. Since identical twins share 100% of their genetic make-up and are presumed to share 100% of their common environment, any increase in risk for binge eating in the co-twin exposed to early alcohol use versus her twin sister who does not report early alcohol use is due to individual-specific environmental factors that influence both the binge eating and early alcohol use. A recent study using this design reported that alcohol use before age 15 years may contribute to the development of binge eating and compensatory behaviors by individual-specific environmental factors.⁶ By including information at multiple time points, the discordant twin design can also provide clues into what may cause the association between two traits.

3. Twins can enhance findings from other research designs. In recent years, there has been an increased focus on including twins in existing study designs. For example, the Human Connectome Project,⁷ which evaluates human brain connectivity in a community sample of individuals, includes twins to provide additional information on how genetic and environmental effects work together to influence traits, as well as what may cause these traits. Similarly, research has taken information from twins who consistently differ in their body weight over time and applied it to mice to understand the association between the gut microbiome and obesity.⁸ Although not including eating disorders per se, these study designs could be used in future research to provide additional information about genetic and environmental factors influencing eating disorders that simply cannot be done using traditional non-twin populations.

Twins are still useful in research studies and provide important information about disorder risk that cannot be collected in non-twin samples. Ultimately, research that understands how genes and environment (or nature and nurture) work together to influence a trait or disorder needs to use many study designs. This includes both large-scale genetics studies and continued use of twin studies. Combining information from these different study designs will be a critical next step towards understanding disorder risk and eventually finding cures.

References

1. Polderman TJ, Benyamin B, de Leeuw CA, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet 2015;47:702-9.
2. Trace SE, Baker JH, Penas-Lledo E, Bulik CM. The genetics of eating disorders. Ann Rev Clin Psych 2013;9:589-620.
3. Munn-Chernoff MA, Keel PK, Klump KL, et al. Prevalence of and familial influences on purging disorder in a community sample of female twins. Int J Eat Disord 2015;48:601-6.
4. van Dongen J, Slagboom PE, Draisma HH, Martin NG, Boomsma DI. The continuing value of twin studies in the omics era. Nat Rev Genet 2012;13:640-53.
5. Suisman JL, Burt SA, McGue M, Iacono WG, Klump KL. Parental divorce and disordered eating: An investigation of a gene-environment interaction. Int J Eat Disord 2011;44:169-77.
6. Munn-Chernoff MA, Grant JD, Bucholz KK, et al. Bulimic behaviors and early substance use: Findings from a cotwin-control study. Alcohol Clin Exp Res 2015;39:1740-8.
7. Van Essen DC, Ugurbil K, Auerbach E, et al. The Human Connectome Project: A data acquisition perspective. Neuroimage 2012;62:2222-31.

8.              Ridaura VK, Faith JJ, Rey FE, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013;341:1241214.