Okay, wow, your analysis is far more interesting than the paper itself, but I'm going to add my $0.02 in case anyone wants it.

Right off the bat, WES studies and GWAS are currently next-to-useless, in terms of predictive power and mechanistic insight, for complex conditions. But the last time I looked at WES and GWAS in the context of complex diseases was years ago and that's just my opinion.

A primary limitation of this study was that it included only 30 subjects...

You think?

And a control cohort of 88, with the same number of TIMs and Ms who aren't TI.

... though this does constitute a larger sample size than the majority of prior studies utilizing WES to study gender dysphoria.

I can't figure out which prior WES studies they're referring to, since this paragraph doesn't cite anything. [24] does seem to be a WES project with... 9 TIFs and 4 TIMs. LMAO. Let's see---the next one I can't access from home, the next is a review, and [27] has a pretty sweet cohort of 380 TIMs, and they chose their 12 genes based on a lit review rather than WES.

The authors don't mention whether their findings are consistent with previous genetic studies. They're posing new candidate genes rather than looking to confirm existing results, so it's not a huge issue. They do filter out results that appear in dbSNP. I'm just curious.

I can't get that one review paper they keep citing that suggests gender dysphoria has a genetic component ([22]), but will download it the next time I'm on campus.

K, so how widespread are these mutations?

With the exception of a variant of DIAPH2, which is localized to the X chromosome, each variant was observed in only a single subject, and all were heterozygous.

In general, all frameshift variants were heterozygous, including a variant of PPP2R3B, c.356dupC (p.P119fs), located on chromosome X, in one transgender male. One exception to this was noted in a single transgender male, who was homozygous for a variant of PRAMEF13, c.1291_1292insA (p.A431fs).

All splice-region variants were heterozygous and noted in only a single subject.

Variants in this group were heterozygous and only observed in a single individual, unless otherwise noted below.

Okay, so with nine exceptions, most of the variants in Tables 1--4 were observed in only one person out of 30 (and not observed in any of the 88 controls). And because the method the authors chose is just to find new genes that might be related to gender dysphoria, they can't confirm whether these variants do anything, and instead speculate on why these genes might be related to gender dysphoria in the mini review paper that dominates the discussion section. So these long tables are mostly variants that they found in a single person, out of 30, and they don't know which ones are important, or even if any of these are important at all.

We have a lot of genes. I'd guess every single one of us has variants that don't appear in dbSNP and might also not appear in 88 randomly selected people. It's not surprising that they were able to find such variants in their cohort of 30, even restricted to genes that might affect sexual development.

I'm also not seeing anyone's race mentioned anywhere. Sad to say, but WES studies and GWAS have to be super racist by design. People whose ancestry is constrained to a certain region are genetically similar to each other and genetically different from people whose ancestors lived in a different region, in ways that are unrelated to the goal of the study. This does often confound results.

Ooh, and now I'm thinking of how hormone therapy would affect epigenetics. Unfortunately,

In addition, we are unable to characterize the extent of the majority of subjects’ transition processes, as this information was not collected as part of the enrollment process.

And:

However, we did make certain that each subject met the clinical criteria for gender dysphoria before enrollment.

Are they saying only people with gender dysphoria can be trans? TERF TERF TERF TERF TERF

I'm scrolling through Tables 1--4 and recognize a few of these genes. I don't know if this is useful for anyone to hear, but the genes they identify as contributing to sexual dimorphism aren't exclusively developmental. Many of these genes have specific roles that don't neatly relate to sex or gender, and sexual dimorphism is kind of a side gig for them. And:

In contrast to the limited knowledge regarding the development of human gender identity, there has been significant progress, over the last twenty years, using animal models to demonstrate the neurodevelopmental pathways leading to sexually dimorphic brain regions and resultant sex-specific behavior patterns. In rodents, four key areas of the brain have been identified with developmental pathways leading to sexual dimorphism...

The key phrase here is 'in rodents.' Do the authors know of any studies on sexual dimorphism in humans?

Lastly, in addition to the two paragraphs in the intro about how bad trans kids have it (not related to the content of the study), the subsection in Discussion titled 'Special considerations...' suggests that the authors want their work to lend legitimacy to gender dysphoria claims, meaning that they are not addressing the question "is there a genetic component to gender dysphoria?" but rather "there's probably a genetic component to gender dysphoria, what is it?" These claims don't have anything to do with the study and suggest the authors are biased towards one hypothesis over another (that gender dysphoria has a genetic component), but this study says so little that this bias wouldn't affect their results. It's only dangerous here because laypeople like the one in OP's title don't realize that this paper does nothing to confirm or support this hypothesis.

Is it the case that every single gene in Tables 1--4 is associated with ASD? That's what I interpreted your title to mean. I don't see any mention of CNTNAP2/CASPR2, in particular, and I see DIAPH2 but not DIAPH3.

So, what this paper is saying is "we think gender dysphoria has a genetic link. If it does have one, it's complicated. We tried to find some genes that are different in trans and non-trans people. We have an idea of how these genes are linked to gender and are telling other scientists about these genes because we think they might be interesting." In particular, these authors start out by assuming gender dysphoria has a genetic component, so they can't prove that gender dysphoria has a genetic component. Link to ASD or not, this paper does not prove that gender identity is innate, as whoever posted this study claims.

(Edit: typo)