The goal of this chapter is to help every reader grasp the complex interaction between genotype and phenotype. This is not easy. For decades, in many nations, millions of scientists have struggled to understand this complexity. Each year brings advances in statistics and molecular analysis, new data to uncover various patterns, all resulting in hypotheses to be explored.

Now we examine two complex traits: addiction and visual acuity, in two specific manifestations, alcoholism and nearsightedness. As you will see, understanding the progression from genotype to phenotype has many practical implications.

At various times throughout history, people have considered the abuse of drugs to be a moral weakness, a social scourge, or a personality defect. Historically and internationally, the focus has been on alcohol, since people everywhere discovered fermentation thousands of years ago. Alcohol has been declared illegal (as in the United States from 1919 to 1933) or considered sacred (as in many Judeo-Christian rituals), and people with alcoholism have been jailed, jeered, or even burned at the stake.

We now know that inherited biochemistry affects alcohol metabolism; punishing those with the genes does not stop addiction. There is no single “alcoholic gene,” but alleles that make alcoholism more likely have been identified on every chromosome except the Y (Epps & Holt, 2011).

86

To be more specific, genes create an addictive pull that can be overpowering, extremely weak, or somewhere in between, as each person’s biochemistry reacts to alcohol by causing sleep, nausea, aggression, joy, relaxation, forgetfulness, sex urges, or tears. Metabolism allows some people to “hold their liquor” and therefore drink too much, whereas others (including many East Asians) sweat and become red-faced after just a few sips, an embarrassing response that may lead to abstinence. This inherited “flushing” tendency not only makes alcohol addiction rare, but it also improves metabolism of alcohol (Kuwahara et al., 2014).

Although the emphasis at first was on the genes that cause biological addiction, we now know that genes that affect personality traits may be pivotal (Macgregor et al., 2009). Temperamental traits known to be inherited, among them a quick temper, sensation-seeking, and high anxiety, all encourage drinking.

Sex (biological—either XX or XY) and gender (cultural) also affect the risk of alcoholism. For biological reasons (body size, fat composition, metabolism), women become drunk on less alcohol than men, and women who are heavy drinkers double their risk of mortality compared to men (Wang et al., 2014).

Many cultures encourage men to drink but not women (Chartier et al., 2014). For example, in Japan, both sexes have the same genes for metabolizing alcohol, yet women drink only about one-tenth as much as men. When women of Japanese ancestry live in the United States, their alcohol consumption increases. Apparently, Americans of Asian decent try to adopt the drinking patterns of their new culture (Makimoto, 1998).

Age, genes, and culture affect vision as well. The effects of age are easy to notice. Newborns focus only on things within 1 to 3 feet of their eyes; vision improves steadily until about age 10. The eyeball changes shape at puberty, increasing nearsightedness (myopia), and again in middle age, decreasing myopia. The effects of genes and culture on eyesight are more complex, as you will see.

87

A study of British twins found that the Pax6 gene, which governs eye formation, has many alleles that make people somewhat nearsighted (Hammond et al., 2004). Heritability was almost 90 percent, which means that if one monozygotic twin was nearsighted, the other twin was almost always nearsighted, too.

However, heritability indicates only how much of the variation in a particular trait, within a particular population, and in a particular context and era can be traced to genes. For example, the heritability of height is very high (about 95 percent) when children receive good medical care and nutrition, but low (about 20 percent) when children are malnourished. Thus, the 90 percent heritability of nearsightedness among the British may not apply elsewhere.

Indeed, it does not. In some African communities, vision heritability is close to zero because severe vitamin A deficiency makes vision depend much more on diet than on genes. If a child has no vitamin A, that child may become blind, even if the genotype is programmed for great vision. Scientists are working to develop a strain of maize (the local staple) that is high in vitamin A. If they succeed, heritability will increase and overall vision will improve (Harjes et al., 2008).

What about children who are well-nourished? Is their vision entirely inherited? Cross-cultural research suggests that it is not (Seppa, 2013).

One report claimed that “myopia is increasing at an ‘epidemic’ rate, particularly in East Asia” (Park & Congdon, 2004, p. 21). The first published research on this phenomenon appeared in 1992, when scholars noticed that, in army-mandated medical exams of all 17-year-old males in Singapore, 26 percent were nearsighted in 1980 but 43 percent were nearsighted in 1990 (Tay et al., 1992). A recent article in the leading British medical journal suggests that, although genes are to blame for most cases of severe myopia, “any genetic differences may be small” for the common nearsightedness of Asian school children (I. Morgan et al., 2012, p. 1739). Nurture must somehow be involved. But how?

One possible culprit is homework. As Chapter 12 describes, contemporary East Asian children are amazingly proficient in math and science. Fifty years ago, most Asian children were laborers; now almost all are diligent students. As their developing eyes focus on their books, those with a genetic vulnerability to myopia may lose acuity for objects far away—which is exactly what nearsightedness means.

A study of Singaporean 10- to 12-year-olds found a positive correlation between nearsightedness (measured by optometric exams) and high achievement, especially in language proficiency (presumably reflecting more reading). Correlation is not proof, but the odds ratio was 2.5 and the significance was 0.001, which makes this data impossible to ignore (Saw et al., 2007).

Data from the United States on children playing sports has led some ophthalmologists to suggest that the underlying cause of myopia among Americans is too little exposure to daylight (I. Morgan et al., 2012). Perhaps if children spent more time outside playing, fewer would need glasses.

Between the early 1970s and the early 2000s, nearsightedness in the U.S. population increased from 25 to 42 percent (Vitale et al., 2009). Urbanization, television, and fear of strangers have kept many U.S. children indoors most of the time, unlike children of earlier generations who played outside for hours each day. One ophthalmologist comments that “we’re kind of a dim indoors people nowadays” (Mutti quoted in Holden, 2010, p. 17). Formerly, genetically vulnerable children did not necessarily become nearsighted; now they do.

88

Since genes affect every disorder, no one should be blamed or punished for inherited problems. However, knowing that genes never act in isolation allows prevention after birth. For instance, if alcoholism is in the genes, parents can keep alcohol out of their home, hoping their children become cognitively and socially mature before imbibing. If nearsightedness runs in the family, parents can play outdoors with their children every day.

Of course, outdoor play and abstention from alcohol are recommended for all children, as are dozens of other behaviors, such as flossing, saying “please,” getting enough sleep, eating vegetables, and writing thank-you notes. No parent can enforce every recommendation, but awareness of genetic risks can guide priorities.

89