Study Strongly Links Genetics, Homosexuality

Federal researchers say they have uncovered the strongest evidence yet that homosexuality is genetic in origin.

Studies in 40 families in which two brothers are gay suggest that much male homosexuality may have its roots in a gene located in a small region of the X chromosome, the sex-linked chromosome that men inherit from their mothers, according to a report published today in the journal Science.

The researchers, led by molecular geneticist Dean H. Hamer of the National Cancer Institute, are racing to identify the specific gene from among the 100 or more genes located in that region.

Although the isolation of the gene is likely to lead to the first molecular understanding of how homosexuality develops, the discovery may have a broad impact in the study of general behavior.

“This is the first time that we have a window on human behavior and the genes that affect it,” said Dr. Elliot Gershon, chief of the clinical neurogenetics branch at the National Institute of Mental Health. “It’s a major breakthrough in behavioral genetics. . . . (No other known genes) are tied to behavior in a normally functioning brain.”

“The idea that behavioral traits can be traced to a specific gene is something that has only been theoretical up to this point,” said sociologist Pepper Schwartz of the University of Washington. “The whole nature of what we understand to be human behavior will have to be re-evaluated” to understand the genetic links, she said.

But Gershon and others, including Hamer, caution that the study needs to be replicated for credibility. In recent years, other researchers have reported similar genetic links to such mental disorders as schizophrenia and manic depression, only to have the link disappear when more data was compiled or the original data was reanalyzed.

“There is almost no finding that would be convincing by itself in this field,” Gershon said. Nonetheless, “I think it will be replicated.”

At least three previous studies have linked homosexuality to physiological and genetic differences. Dr. Simon LeVay, then of the Salk Institute in La Jolla, reported in 1991 that he found subtle structural differences between the brains of gay and straight males.

Two other studies of twins, one in males and one in females, have also shown a genetic link to homosexuality but those findings were less direct. In both cases, the researchers found that if one member of a pair of identical twins is homosexual, the second member is also likely to be gay.

Such studies suggest that there is a gene for homosexuality but give no indication where it may be found among the estimated 100,000 genes that make up the human genome.

“We knew there was a genetic influence somewhere, but we didn’t know where,” said Dr. Richard C. Pillard, a psychiatrist at Boston University and a co-author of the two studies of twins. “Now Hamer has come along and found an area on the X chromosome where he thinks there is an actual gene. His was the next logical step.”

Hamer and his colleagues got their first hint about where to look for the gene from their interviews with gay males at AIDS clinics at the National Institutes of Health and elsewhere in the Washington area.

Although they occasionally observed gay fathers and sons in the same family, most familial links were to relatives on the gay male’s maternal side of the family. They found that the incidence of homosexuality among maternal uncles and sons of maternal aunts was four times that of the general population.

This type of inheritance through the mother led them to look at the X chromosome, which is contributed to children only by the mother. Several well-known traits, such as color blindness and male-pattern baldness, are carried by the X chromosome, as are diseases such as Duchenne’s muscular dystrophy, hemophilia and fragile X syndrome, the leading cause of mental retardation.

The team recruited 40 pairs of brothers who are homosexual and studied genetic markers on their X chromosomes. In this technique, which is widely used for tracking the cause of genetic diseases, the researchers obtained blood from the subjects and examined their X chromosomes. They looked for specific genetic markers that are transmitted along with the trait in question--in this case, homosexuality--and that were not present in heterosexual males in the families.

In 33 of the 40 pairs, they found markers in a small region of the X chromosome, indicating that the proposed gene is located in that region.

Hamer was not disappointed that the markers were not found in all the families. “Given the intricacies of human behavior, it is not surprising that a single genetic (region) fails to account for all the variation seen in the study group,” he said. “What is remarkable is that we can account for at least some of the inherited variability with a fair degree of statistical confidence.”

Once the gene is located, researchers have many crucial questions that must be answered: What does the gene do? How does the gene in homosexual men differ from that in heterosexuals? Does the gene invariably lead to homosexuality or are there heterosexual males who carry it? What is the gene’s effect in women, particularly those who have a copy of it on each of their X chromosomes?

The answers to those questions, experts agree, will provide valuable insights into the general mechanisms by which genes influence behavior.

Meanwhile, gay and lesbian groups were generally happy about the new report. “The NIH study . . . shows that homosexuality is a naturally occurring and common variation among humans--a fact that gay and lesbian people have known all along,” said Peri Jude Radecic of the National Gay and Lesbian Task Force.

But Mitzi Henderson, president of Parents and Friends of Lesbians and Gays, cautioned that the results could be a “two-edged sword.” She and others fear that the religious right will campaign for gene therapy or similar measures to “cure” gay people of their “abnormal behavior.”

“Studies of human sexuality are not conducted in political and social vacuums,” Radecic said. “The results must therefore be used in the most ethical ways, and precautions must be taken to ensure that the studies are not used against any individuals or groups.”

The discovery could also have a major impact on laws prohibiting same-sex sexual contact, which is prohibited in 40 states, said Dr. Richard Green, a UCLA psychiatrist who is a lawyer. One of the key constitutional limitations on such discrimination, he said, is that it cannot be based on immutable traits, such as skin color.

The discovery that homosexuality is linked to a specific gene and thus immutable could lead to the courts overturning those laws, as well as eliminating housing and job discrimination based on sexual orientation, he said.