Genetic Causal Factor for Being Transgender: An Update

DNA

I have found some new papers that support the idea that being transgender is a genetic gender predisposition. They are encouraging but somewhat disappointing because of their scope and the biases that their investigators have about sex, gender and prenatal hormones. The studies fall short with respect to their scope—the number of subjects used in them. That is not their fault because there are huge number of samples available from the International Gender Diversity Genomics Consortium and they are already “in the can.” The U.S. NIH has refused to fun large scale studies to look across the entire human genome for transgender markers. The U.S. NIH is one of the few organizations who can fund such “big science.”

Understanding of transgender causation requires broad knowledge of evidence across several scientific areas which many investigators do not have. Many investigators conflate animal sex with human gender behavior and adhere to the refuted Prenatal Testosterone Theory of being Transgender (PTTT). I am constantly fighting this Zeitgeist, the intellectual climate, although the evidence refutes these theories. You will remember that the evidence supports four causal factors, specifically: gender behavior genes, epigenetic unblocking, cultural gender categories and early learning/recognition. I have identified these and given updated information for the evidence supporting these factors and refuting other factors in my transgender science books, in these blog posts and on my The Transgender Scientist podcasts. In 2011 at the WPATH meeting I identified genetics as a factor and this was buttressed by Milton Diamond who showed historical data from his gender clinic in Hawaii which he had gone back and analyzed. I was not the first to recognize a genetic factor, I was just calling on the evidence from previous studies that had been overlooked.

I have previously reported on an oral presentation given by Thiessen et. al. in 2018 from the Medical College of Georgia, which is down the road from me in Augusta. Thiessen (2019) recently provided more detail on this original report. They did full genome scans but only on 17 trans women and 13 trans men. They found about 400 genes with anomalies (there are about 20,000 to 30,000 human genes) but selected out those involved with genes associated with hormonal influence over hypothalamic structures. (The hypothalamus is at the base of the brain and is one of the oldest structure; it’s where several structures have been linked to the influence of testosterone.) This narrowed the candidates to about 21. But some of these 21 only appeared in single individuals.

The good news is that they are doing full genome scans. The bad news is that they have been led to look in places associated with brain sex differences and places where testosterone (via conversion to estradiol) is said to be responsible for PTTT. Yes, those places have different structures, depending on sex. And prenatal testosterone can influence animal sexual behavior. But animal sexual behavior and human gender behavior are quite different. And in transgender people, sex and gender behavior are dissociated, because that is what the definition of being transgender is. Transgender people do not follow the gender category to which they were assigned based on sex assigned at birth. And, especially because they are geneticists, they should know that if one identical twin is transgender and the other is not, they still both have the same sex. I guess I will remain the only vox clamantis in deserto (voice crying in the wilderness) on this insight. (The only reason I know this Latin phrase is that it is the motto of my college)

DNA sequencing from a single cell.

I recently found another transgender genomic analysis paper by Yang, et. al, 2017. This research effort used an entirely different approach from the Thiessen paper. Yang did full genome scanning of transitioned trans men and trans women but only looked for very rare differences as potential markers. Such not normally considered in conventional genome analyses such as Thiessen. They found differences in the RYR3 gene that rarely shows differences. They found structural differences in this gene in 3 of the 9 trans men in the study, but none of the 4 trans women had this anomaly. Of 100 controls, none had such differences. This gene is associated with a network of genes that generally control the flow of ions in the brain. (Brain cells use such ions to transmit signals down their length that eventually reach other neurons.)

As follow-up, they looked for variations in this gene network across the brain and found differences in the hippocampus, the associative striatum, and caudate nucleus. It is a big advance in neuroscience to have the ability to localize the actions of genes in brain structures. These structures are known to be associated with memory, making associations of memories and motor control. You might remember that I have reported on anatomical differences in the putamen structure in transgender people. The putamen is just the front end of the caudate. This network of genes was not common in the hypothalamus. The study was billed as a pilot initial study. Hopefully it has or will be replicated with larger numbers of subjects.

The Yang study shows the value of using different approaches to the problem of identifying genetic markers, since the RYR3 gene was not identified as a marker in the Thiessen report, nor did Thiessen identify any of the genes in the RYR3 network because he was not looking explicitly for rare gene differences. Thiessen only looked for genetic markers that might be associated with the hypothalamus (and the PTTT). I am not going to say I told them so, I never would have believed that they would take this narrow approach. Yang took a broader approach and found markers in other structures. It was also disappointing that Yang did not find a marker for trans women using this method but not surprising because of the small number of subjects compared with the rarity of occurrence in differences in this gene. Genes jump around a lot on the DNA molecule and they are only in their expected position about 65% of the time, so a bigger sample is needed.

The way science should work is now for Thiessen to look for the RYR3 network genes in the samples he has collected, if he has not already. They may be in the 400 gene differences they found but did not think relevant to being transgender. Thiessen should take a sharper look at these 400 and not be overly influenced by the Zeitgeist.

As far as transgender science goes, these two studies have improved our knowledge of genetic markers but we still have a long way to go. Maybe with future changes to NIH policy we may see a full genome, more detailed analysis for transgender marker genes. And then the fun will begin as we explore how these genes are expressed in the nervous system, now that we have new neuroscience research tools for brain localization of genes such as Yang used.

Secon Military Medical University.

Oh, yes, the Yang research was sponsored and carried out by Military Medical Hospital researchers in Shanghai, China. We would not want the Chinese to get ahead of us before we have the data to prevent them from genetic “therapy” to eliminate transgender people! In 2018 when a Chinese researcher edited the genes of twin girls during test tube fertilization ostensibly to prevent HIV there was a universal outcry. This was supposedly without permission from the Chinese government. The world knew about the dangers of this procedure because of existing evidence. Will we have the evidence to prevent the erasure of transgender people through genetic “therapy”? I know many transgender people are concerned about this issue, but hiding our heads in the sand will not help us when the military of a collectivist authoritarian regime is in the hunt. This regime has demonstrated that it does not value the individual.

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Tags: featured, gender research, Identity

Category: Transgender Body & Soul