The English anthropologist Francis Galton (1822–1911), a cousin of Charles Darwin, conducted some of the first reported twin studies. Advancing his cousin's theories of evolution, he performed twin studies in 1876 to investigate the extent to which the similarity of twins changes over the course of development. He is considered the originator of the field of medical genetics because of his considerable contributions to the nature-versus-nurture debate and the research methods he developed for evaluating heritability. Genetic determination is the combination of genes that creates a trait or characteristic, and heritability is what causes differences in those characteristics.
Twin studies, meaning comparisons of identical (monozygotic) twins to fraternal or nonidentical (dizygotic) twins, are performed in order to estimate the relative contributions of genes and environment—that is, the extent to which environmental versus genetic influences operate on specific traits. Twin studies also help to determine the proportion of the variability in a trait that might be due to genetic factors. The studies aim to identify the causes of familial resemblance by comparing the concordance rates of monozygotic twins and dizygotic twins. Monozygotic twins share the same genetic material—they have 100%
of their genes in common—and dizygotic twins share only half their genetic material—they have 50% of their genes in common. Most twin studies report their results in terms of pair-wise concordance rates, which measure the number of pairs, or proband-wise concordance rates, which count the number of individuals.
Monozygotic twins serve as excellent subjects for controlled experiments because they share prenatal environments and those reared together also share common family, social, and cultural environments. Furthermore, studies of twins can both point to hereditary effects and also estimate heritability, a term that describes the magnitude of the genetic effect. The limitations of such studies include the potential to overestimate or underestimate the role of genetics if environmental influences treat twins as more alike or more different than they actually may be. In addition, in some studies it has been difficult to control for other potential causes or sources of variation.
Some of the most conclusive twin study research has analyzed identical and fraternal twins who were raised apart. Researchers have sought to establish whether characteristics such as personality traits, aptitudes, and occupational preferences are the products of nature or nurture. Similar characteristics among identical twins reared apart might indicate that their genes played a major role in developing that trait. Different characteristics might indicate the opposite—that environmental influences assume a much stronger role. By comparing monozygotic and dizygotic twins, investigators can test their hypotheses and confirm the findings of earlier research. For example, if identical twins raised in different homes have many similarities, but fraternal twins raised apart have little in common, researchers may conclude that genes are more important than environment in determining specific characteristics, traits, susceptibilities, and diseases.
A Scandinavian twin study, "Environmental and Heritable Factors in the Causation of Cancer—Analyses of Cohorts of Twins from Sweden, Denmark, and Finland" (New England Journal of Medicine, vol. 343, no. 2, July 13, 2000), reported by Paul Lichtenstein et al., looked at nearly 45,000 pairs of twins to determine if the likelihood of developing certain kinds of cancers is more closely linked to environmental exposures than genetics. The results of this large-scale study revealed that environmental factors are linked to twice as many cancers as genetic factors. In fact, the risk of developing only three types of cancer (albeit some of the most common cancers)—breast, colorectal, and prostate cancers—show a significant genetic correlation.
Prostate cancer is found to have the strongest genetic link, with 42% of risk explained by genetic factors and 58% by environmental factors. The other cancers with a demonstrable genetic link, breast and colorectal cancers, are found to have less than a 35% link to genetics.
Drug use, abuse, and dependence among female twin pairs,
SOURCE: "Drug Use, Abuse, and Dependence Among Female Twin Pairs," in "Twin Studies Help Define the Role of Genes in Vulnerability in Drug Abuse," NIDA Notes: Research News, vol. 14, no. 4, U.S. Department of Health and Human Services, National Institute on Drug Abuse of the National Institutes of Health, November 1999, http://www.drugabuse.gov/NIDA_Notes/NNVol14N4/Twins.html (accessed February 5, 2005)
Lichtenstein and his colleagues concluded that inherited genetic factors make a minor contribution to susceptibility to most types of cancer.
Twin Studies Shed Light on Substance Abuse
Research supported by the National Institute on Drug Abuse (NIDA, which is part of the National Institutes of Health [NIH]) has tried to pinpoint the role genes play in predisposing individuals to drug abuse. For example, Kenneth Kendler and Carol Prescott reported in "Cocaine Use, Abuse, and Dependence in a Population-Based Sample of Female Twins" (British Journal of Psychiatry, vol. 173, no. 10, 1998) that genetic factors played a major role in patterns of progression from marijuana and cocaine use to abuse by female twins. The study finds that concordance rates—both twins using, abusing, or being dependent on drugs—were higher for identical twins than for fraternal twins. For cocaine use, concordance was 54% in identical twins and 42% in fraternal twins; for abuse, 47% in identical twins and 8% in fraternal twins; and for dependence, 35% in identical twins and zero for fraternal twins. (See Figure 4.1.)
The research supports earlier studies that indicated family and social environmental factors are influential in determining whether an individual begins using drugs. The more significant finding was that progression from drug use to abuse or dependence (as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, American Psychiatric Association, Washington, DC, 1994) was due largely to genetic factors. For cocaine and marijuana, approximately 60% to 80% of the differences in abuse and dependence between fraternal and identical twin pairs were attributable to genetic factors.
Another NIDA-supported study conducted by Ming Tsuang et al. ("Co-occurrence of Abuse of Different Drugs in Men," Archives of General Psychiatry, vol. 55, 1998) looked at 1,874 pairs of identical male and 1,498 fraternal male twin pairs to see if genetic influences contributed to susceptibility for abusing drugs. Tsuang and colleagues found that genetic influences are stronger for abuse of some drugs than for others and that abusing any category of drugs such as sedatives, stimulants, opiates, or heroin is associated with a marked increase in the probability of abusing every other category of drug. The study also reveals that each category of drug addiction has unique genetic influences and, not surprisingly, heroin is the drug with the greatest genetic influence for abuse. Other NIDA-sponsored twin studies suggest that genetic factors for drug abuse or dependence are stronger in males than in females.
Do Genes Govern Sexual Orientation?
The role of genetics in establishing sexual orientation (the degree of sexual attraction to men or women) and its link to homosexuality have been hotly debated in the relevant scientific literature and the media. Studies of identical twins have revealed that sexual orientation, like the overwhelming majority of human traits and characteristics, is not exclusively governed by genetics, but is more likely the result of a gene-environment interaction. For example, if homosexuality was exclusively controlled by genes then either both members of a set of identical twins would be homosexual or neither would be. Multiple studies have shown that if one twin is homosexual his or her sibling is also homosexual less than 40% of the time.
Michael Bailey et al. systematically evaluated gender identity and sexual orientation of twins and reported their findings in "Genetic and Environmental Influences on Sexual Orientation and Its Correlates in an Australian Twin Sample [Personality Processes and Individual Differences]" (Journal of Personality and Social Psychology, vol. 78, no. 3, March 2000). Bailey et al. observed that both male and female homosexuality appears to run in families and that studies of unseparated twins suggest that this is primarily due to genetic rather than familial environmental influences. They also observe that previous research suffers from limitations such as recruiting subjects via publications aimed at homosexuals or by word of mouth—strategies likely to bias the samples and results.
To overcome these limitations, Bailey and his colleagues assessed twins from the Australian Twin Registry rather than sample those recruited especially for the purpose of their research. Using proband-wise concordance (an estimate of the probability that a twin is nonheterosexual given that his or her co-twin is nonheterosexual), they found lower rates of twin concordance for nonheterosexual orientation than in previous studies. The most striking difference was between the researchers' proband-wise concordance rates and those of past twin studies of sexual orientation. Previously, the lowest concordances for single-sex identical twins were 47% for women and 48% for men. This study documents concordances of just 20% for women and 24% for men, significantly lower than the rates reported for the two largest prior twin studies of sexual orientation. Bailey et al. concluded that sexual orientation is familial; however, their study does not provide statistically significant support for the importance of genetic factors for this trait. They caution that this does not mean that their results entirely exclude heritability. In fact, they consider their findings consistent with moderate heritability for male and female sexual orientation, even though their male monozygotic concordance suggests that any major gene for homosexuality has either low penetrance or low frequency.
Bailey and the other researchers attributed their markedly different results to the observation that in prior studies twins deciding whether to participate in research that was clearly designed to study homosexuality probably considered the sexual orientation of their co-twins before agreeing to participate. In contrast, the more general focus of the Bailey study and its anonymous response format made such considerations less likely.
While it remains unclear from recent studies whether concordance is closer to 50% or 30%, all researchers concur that it is not 100%. This finding suggests that the influence of genes on sexual orientation is indirect and influenced by environment. Neil Whitehead, author of My Genes Made Me Do It! A Scientific Look at Sexual Orientation (Lafayette, LA: Huntington House, 1999), claims that "genes make proteins, not preferences." Similarly, Whitehead contends that "genes create a tendency, rather than a tyranny" and concludes that all of the identical twin studies reveal that in terms of determining sexual orientation, neither genetic nor family-related factors are overwhelming. Furthermore, Whitehead believes that all influences—genetic and environmental—are subject to change and that it is possible to "foster or foil genetic or family influences."