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Q & A Concerning the March 2005 Human Genetics study concerning sexual orientation in men.


Warren Throckmorton, PhD (Reviewed by Durwood Ray, PhD, Professor of Biology, Grove City College)


To readers coming here from the NARTH (National Association for Research and Therapy) website. The article below is in reference to one study and does not reflect my complete views on the biology of sexual orientation. I believe there are some genetic components to sexual orientation as well as possibly some hormonal influences during the pre-natal period. The jury is out on the matter of how much pre-natal influence there might be on sexual orientation so it is premature to say much more. I am pretty convinced that the usual environmental factors (e.g., parenting) is of relatively small significance. I also currently believe that sexual orientation, once set, is durable. Some people may change to varying degrees but we do not know enough to give a sure prognosis.

Warren Throckmorton, PhD
3/10

Information about the article, "A genomewide scan of male sexual orientation" by B. Mustanski, et al, published in the March 2005, issue of Human Genetics.

LINKS

- Mustanski, B.S., DuPree, M.G., Nievergelt, C.M., Bocklandt, S., Schork, N.J. & Hamer, D.H. (2005). A genomewide scan of male sexual orientation. Human Genetics, 116(4), 272-278.

- News Release from the University of Illinois - Chicago concerning the study.

- FOXNews article "Genes Linked With Male Sexual Orientation Found."

- Helpful summary and Q&A from Dr. Mustanski concerning the study.

- News Release from Drs. Throckmorton & Ray - 2/9/05

- Dr. Daryl Bem's work concerning the Exotic Becomes Erotic theory


Q & A Concerning the March 2005 Human Genetics study concerning sexual orientation in men.

(NOTE: This section is subject to change. Posts will be added as needed)

Q. When you refer to the “gay gene theory,” what do you mean?

A. We refer to two ideas: one, that one gene has been found or will be found that controls the expression of homosexual (or heterosexual for that matter) attractions and two, that a gene or genes has been or will be found that directly determines the direction of one’s sexual affections.

Q. How does the study in Human Genetics undermine the gay gene theory?

A. First of all, the study located only one region that meets the criteria for suggestive linkage but does not meet the higher standards of either significant or highly significant linkage. The authors also discuss three other regions (if you include Xq28) that may relate in some way to sexual orientation. Thus, the notion that there is one gay gene is undermined by the results of this report. As we noted in our review, the co-lead author of the study, Dr. B Mustanski, indicated that he believes sexual orientation to be too complex for it to be linked to one gene.

Secondly, nothing in this report supports inferences such as made by a FOXNews report: “Genes Linked with Male Sexual Orientation Found.” The authors of the research report speculate about what genes might be in the regions of DNA they isolated but there is no confirmation by this report that these genes indeed are involved. We disagree with the following statement made by Dr. Mustanski in a press release about the study: "Our study helps to establish that genes play an important role in determining whether a man is gay or heterosexual.” We believe that statement to be quite speculative in light of the potential for false positives and in light of the fact that we have no idea how the putative gene or genes may relate to sexuality. We do however agree with Dr. Mustanski when he states, “The next steps will be to see if these findings hold up in a new sample and then identify the particular genes within these newly discovered chromosomal regions.” Here he acknowledges, as the research team does in the Human Genetics article that no genes have as yet been discovered.

Third, we speculate that any regions discovered by linkage analysis to be related to sexual orientation will better fit an indirect influence model as opposed to a model that proposes genes directly wire the brain to response sexually to those of the same sex. We further believe that there may be different genes for different people that could influence temperament in such a way same sex attractions may arise in interaction with certain environmental conditions. Our reason for referring to the work of Daryl Bem was to provide another perspective on the results of genetic research such as the linkage study by Mustanski et al.

Q. What do mean by “temperament interacting with environment?”

A. Our view is that genes or other biological factors do not code directly for sexual attractions but rather for childhood temperamental factors such as activity level, aggressiveness and perhaps novelty seeking. These temperamental traits will predispose children to prefer activities that are either gender conforming or gender non-conforming. Those children who prefer gender non-conforming activities develop feelings of difference from same sex peers and come to view those of the same sex as being other than them, akin to being the opposite sex. Thus, depending upon many variables in the environment, temperamental traits could create a sense of difference and cause questioning one’s sexuality. We follow here pretty closely the Exotic Becomes Erotic theory of Daryl Bem of Cornell University. We think genes such as may be discovered through linkage studies may tell us something about how preferences for activity level and type and aggressiveness may be inherited. For more about Dr. Bem’s work, please see the link above.


Q. What is a genomewide scan?

A. Since the unraveling of the human genome in 2001, it is now possible to scan the entire genome, in a sense, fishing for genetic contributions to complex human traits or disease states. In so doing, investigators assume that there may be more than one gene that is responsible for the trait in question. Such scans rely on large numbers of sibling pairs or other family members to be involved who share the trait in question (in the case of the Mustanski et al study, homosexuality).

Investigators do DNA analysis to look for siblings or family members that share DNA sequences on various sections of the genome. Matches on certain points are then assumed to relate to the target trait.

Q. What is linkage?

A. The linkage approach used in the Human Genetics study refers to shared sequences among family members. The Mustanski et al study sought to determine if certain DNA sequences were shared in pairs of self-identified gay brothers more often than would be expected by chance.

Q. What are the criteria for determining whether linkage exists or is significant?

A. Criteria have been suggested by geneticists Lander and Kruglyak.(1) They are as follows:

Degree of significance Lod score
Suggestive.................2.2
Significant................3.6
Highly significant.........5.4

Comparing the LOD scores in the criteria and those found in the Mustanski et al study shows that only one score reaches the level of suggestive linkage, the 3.46 LOD on chromosome 7q36. In our review of the study we noted that this score does not achieve the 3.6 level for a significant finding. We have been asked to clarify that the 3.46 LOD score does suggest there may be linkage. However, the history of linkage studies gives strong support to Lander and Kruglyak’s caution to use the higher scores as indicative of higher probability that the finding is a true one, especially given the fact that sexual orientation is a complex behavioral trait. The level of suggestive linkage means that the one finding is potentially a false positive. Given the potential for false positives, we urge caution in interpreting the findings of Mustanski et al. On the other hand, Dr. Mustanski said about the study: "Our study helps to establish that genes play an important role in determining whether a man is gay or heterosexual.” We believe that statement to be quite speculative in light of the potential for false positives and in light of the fact that we have no idea how the putative gene or genes may relate to sexuality. An examination of other linkage research efforts (e.g., schizophrenia) demonstrates how contradictory linkage results can be and how caution is warranted in assuming a hit is in fact real.(2)

We do however agree with Dr. Mustanski when he states, “The next steps will be to see if these findings hold up in a new sample and then identify the particular genes within these newly discovered chromosomal regions.” More conservatively, we anticipate that further genomewide scans will be done with false positives likely. As with other complex behavioral traits, we further anticipate that other areas of the genome may be implicated by other researchers, thus complicating the picture.

It is important to note what the study did and did not do:

From our reading of the published report, here is what we believe the study did:

• The researchers found 3 locations in the genome where self-identified gay and bisexual brothers share DNA sequences between 8-12.5% greater than expected by chance.
• In one location, 7q36, the gene sharing was great enough to be considered suggestive that the DNA sequence might be close to a gene that controls or influences sexual orientation.
• The other two regions where sharing was greater than chance did not reach a level of sharing that would permit the researchers to say the location may be linked to a potential gene influencing sexual orientation. However, the researchers reported these regions because they cannot absolutely rule out that a gene influencing sexual orientation might be involved or close by.
• In examining region Xq28, the study did not find linkage in the full sample. However, the reanalysis of the prior work of Hamer (1993) found a highly suggestive linkage in that sample of subjects. The authors speculate that perhaps Xq28 could implicated in the development of sexual orientation for some people and not for others.

Here is what we believe the study did not do:

• The study did not find genes that directly organize the brain to respond sexually to those of the same sex.
• It did not specify what genes may actually be involved in sexual orientation.
• It did not provide any specificity in how the DNA locations identified could impact people to develop sexual attractions of any kind.

(1) Lander, E. and Kruglyak, L. (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genetics, 11, 241-247.

(2) Gurling, et al. (2001). Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia on chromosomes 11q23.3-24 and 20q12.1-11.23. American Journal of Human Genetics, 68, 661-673.



Please contact Dr. Throckmorton (ewthrockmorton@gcc.edu) if you believe anything in the above information is in error or you have questions concerning these documents.

 

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