Study Questions Gene Influence on Male Homosexuality

April 23, 1999; New York Times


Underscoring the difficulty scientists face in finding genes that underlie complex human behaviors, a team of researchers are reporting Friday that they have been unable to confirm a widely publicized study linking male homosexuality to a small region of one chromosome.

Experts in behavioral genetics say the new report, which appears in the journal Science, does not invalidate the notion that genes influence sexual orientation, which many scientists believe is the case, on the basis of other types of studies. Nor do the new results completely rule out the possibility that a gene or genes for homosexuality lie on the chromosome in question, the X-chromosome.

The difficult task of detecting genes that influence complex behavior.

But the failure to replicate the earlier study is typical of the zigzagging course of research efforts to ferret out genes that influence complicated traits, or that contribute to illnesses with a behavioral component, like schizophrenia, manic depression, alcoholism and hypertension.

And since the question of whether homosexuality is innate is politically charged, the new findings will very likely revive discussion of the issue.

In the new study, a team of Canadian researchers tried to replicate work by Dean Hamer, a geneticist at the National Cancer Institute. In a 1993 study of 40 pairs of homosexual brothers, Hamer reported that in 33 of the pairs -- more than would be expected by chance -- an area on the bottom half of the X-chromosome was identical, indicating that one or more genes in that region, called Xq28, could be connected to the brothers' sexual orientation.

In men, the X-chromosome is inherited from the mother. It pairs with the Y-chromosome to form the so-called sex chromosomes, the last of the 23 pairs of chromosomes that appear in all cells of the human body.

A second study by Hamer's laboratory, published in 1995, also found evidence for such a link, though the effect seen was smaller.

But the Canadian researchers, who studied 52 pairs of homosexual brothers, concluded that their results "do not support an X-linked gene underlying male homosexuality."

"I feel these findings need to be taken seriously," said Neil Risch, professor of genetics and statistics at Stanford University, who performed the statistical analysis of the data for the new study and is a co-author on the paper. "If there is an effect there, it is pretty small."

Other scientists greeted the new findings with interest and caution. Dr. Kenneth Kendler, the Banks distinguished professor of psychiatry at Virginia Commonwealth University, said none of the studies so far was large enough for scientists to reach a firm conclusion about whether such a gene is present on the X-chromosome.

"There are now three reports that produce data relevant to this question," Kendler said, "one strongly positive, one modestly positive and one strongly negative. Does this new report show conclusively that there is no evidence? No, that is too strong."

Detecting genes that influence complicated traits is a formidable task, he said, and current technology is limited. "Fifty years from now we're going to look back at this and say we were toddlers stumbling around in a playpen," Kendler said. "This is a raw science at this stage."

It is also a highly contentious one. As news of the research spread this week, Hamer, the author of the original report, and the Canadian investigators offered conflicting interpretations of the results.

Hamer contended that the Canadian team, led by Dr. George Rice at the University of Western Ontario, did not find the gene linkage because the families of the brothers they studied were not representative of those likely to have an X-linked gene, as indicated by the number of homosexual relatives on the mother's side. The researchers, Hamer said, identified 182 families, but only obtained DNA from 48. These families "were not a random subset," he said, and had the others been included the gene linkage might have been found.

The new study, Hamer contended in a telephone interview, shows only "that not every case of male homosexuality is linked to the X-chromosome."

"I think the question of whether there is a gene on the X-chromosome will be ultimately resolved by either finding the gene or not finding the gene," Hamer said.

Rice responded in an e-mail that selection of the study's participants was "totally random." He said that only 48 families were included because "we could not get blood samples from the rest." And the researchers said the families in their study were "not very different" from those studied by Hamer.

David Smith, spokesman for the Human Rights Campaign in Washington, the largest national gay and lesbian lobbying group, said that although studies indicated there was a biological basis for sexual orientation, the evidence was still inconclusive.

"In the final analysis," Smith said, "we don't believe these studies should have a significant influence in the public policy debate on whether to treat gay and lesbian people fairly and equally, whether they conclusively prove a 'gay gene' or not."