Too Many Monkeys Jumping on the Bed

It’s been a few weeks since the cheatin’ gene AVPR1a made a splash, and I finally found a little time to write about it, so I hope the story hasn’t gotten too stale. I put Dr. Phil as a placeholder to force me to write this, and I was getting really sick of looking at his ugly mug. What he says isn’t that bad, though. In general, the coverage is better than I would have expected, with a fair number of caveats, but the headlines—Oy Vey! Language Log compiled a great list of AVPR1a gene headlines:
"Is monogamy genetic?"; "Baby, my genes made me do it"; "Some men carry 'commitment-phobia' gene"; "Is Lover Boy a Louse? It May Be Genetic"; "Infidelity: It's All In the The Genes"; "Would you abort George Clooney?"; "Study: For men, genetics might untie marital bonds"; "Marriage Woes? Husband's Genes May Be At Fault"; "Marriage problems? Husband's genes may be to blame"; "Study Finds Fear of Commitment May Be in a Man's Genes"; "Commitment phobes can blame genes: A man's reluctance to marry may be down to a genetic 'flaw', say researchers"; "Marital crisis? Blame it on male genes"; "'Bonding Gene' Could Help Men Stay Married"; "Divorce gene linked to relationship troubles"; "Scientists Discover the Monogamy Gene"; "Gene Variant Holds The Key To A Long And Happy Marriage"; etc., etc.
Nuanced soundbites just don’t have that zing!

The Today show had the following piece, which reached the right conclusions, but for all the wrong reasons. My favorite part was their resident expert asserting that the "one-night-stand gene" was necessary for cave-men to raise armies. The video includes two women-on-the street encounters, one pro-genetic testing "to be sure", the other opposed because, "relationships have to be founded on trust so you just have to trust your partner.” Yeah, but what if your partner has the lying gene along with the cheating gene? Bet you’d wished you’d done the genetic vetting then. The correct takeaway message from the video is that it is the phenotype, meaning genes plus environment, that determines behavior. So if you use AVPR1a as an indicator of future behavior you're gambling either way.

What the study really found was that there was a small but statistically significant correlation--this was an observational, not an experimental study--between the presence of the RS3 polymorphism (allele 334) on the AVPR1a gene and reported satisfaction in a relationship. The AVPR1a gene codes for vasopressin (or AVP) hormone receptors in humans, and is the equivalent of the V1aR gene in voles, those cuddly rodents that get so much attention because they form monogamous pairs. Well, some do. There are three highly related species—prairie, montane, and meadow—that are almost identical but behave in radically different ways. Prairie vole males form long-lasting pair bonds and help take care of the roost, whereas meadow and montane voles are known for their slutty dead-beat dads. Turns out if you give prairie vole males a V1aR antagonist, to block the vasopressin hormone from binding they start acting like their meadow and montane brethren, and if you give meadow or montane voles a nice big hit of vasopressin they start acting like true gentlemen scholars. So it is not extraordinary that they found this effect associated with AVPR1a.

The researchers looked at 552 same sex twin pairs and their partners participating in the Swedish Twin and Offspring Study, TOSS. I wish I could have a sample size like that. (As soon as I can get NIH to cough up millions of dollars . . .) So all these twins and their partners filled out several questionnaires and gave up saliva samples, and then the mathemagicians went to work looking for associations between gene length and self-reported behavior.

The authors were pretty slick in calling their main questionnaire the Partner Bonding Scale, stating that it was derived from “behavioral patterns observed when measuring features of pair-bonds among nonhuman primates,” which is a smooth way to try to influence scientists who have been doing research on this topic. Tell people on the street that you are doing research on pair-bonding and you are going to get a lot of blank stares, but it means a socially monogamous relationship, when two individuals cooperate to raise offspring or share resources over an extended period of time.

The questions in the Partner Bonding Scale included questions such as: 
  • You and your partner are involved in common interests outside the family.
  • You and your partner have a stimulating exchange of thoughts.
  • You and your partner calmly discuss something.
  • Have you ever regretted getting married/moving in?
  • Do you kiss your partner?
You can evaluate for yourself if they correlate to pair-bonds for monkeys (IK, IK, and apes). I get the impression that some of these came from the back of a Cosmo magazine. Not that there’s anything wrong with that. I am actually very impressed by the strong association between the presence of the 334 allele and kissing.

Mean scores on the Partner Bonding Scale were associated with the presence of the RS3 polymorphism (bonferroni corrected P<0.01, and the mean PBS score was significantly lower among men carrying copies of the 334 allele (corrected P<0.001). RS3 was not significant for women. Further, the PBS score was dose-dependent, meaning that relationship satisfaction decreased as the RS3 polymorphism grew from one to two 334 alleles.

The study authors then cherry-picked two questions to look at incidence of behavior, and found that 15% of the study participants with no copies of the 334 allele reported marital crisis or threat of divorce, compared to 34% of the men with two copies of the 334 allele. The authors claim this suggests that the presence of the 334 allele doubles the risk of marital crisis. They don’t discuss if it simply doubles the risk of honesty. Even though all participants had been in a relationship for five-plus years, many of the couples in the study were unmarried, and they found this common law status associated with 32% of 334 homozygotes, compared to 17% among those with no copies of the 334 allele. Put another way, 334 homozygotes still exhibited a 68% risk of being married. But they ONLY looked at couples who had been together at least five years, so it is an open question if any of this translates to a general population. Although almost all couples in the study had children, they don't discuss controlling for age or number of children.

If you have the TOSS at your disposal, why not examine unattached individuals as well? This is either a piggy-back study—a crippling limitation, or they are not reporting all results. There is a lot unstated in this article. The only variables they report examining are sex, marriage status, and recent relationship distress. Either the peer reviewers fell asleep at the wheel on this one, or the editors were too excited about all the press this would generate for PNAS. That’s not to say the study isn't important, but too much was left unsaid. For example, why is there no mention of OTXR, the oxytocin receptor gene? Oxytocin and vasopressin are both protein hormones composed of nine amino acids, with a two amino acid difference between the two. The vole literature on vasopressin is significant, but dwarfed by the oxytocin literature. And, although vasopressin might have a stronger role in males than females, oxytocin has a clearly established and causal effect on social relationships in both sexes and across species. If they did not find a relationship between OTXR and the PBS, that would be important to know and replicate. Also, what about genes such as CD38 that play a role in oxytocin expression? Receptors are one thing, endocrine expression is another. What if the reported differences in the PBS are also tied to differences in endocrine expression? If you aren’t getting enough peptide to the receptor it won’t bind and make you want to kiss your partner, regardless of how many receptors you have. There is growing evidence of the environmental role played by early stressors in the development of the oxytocin delivery system, including human evidence, and presumably the vasopressin delivery system as well, but the effect this might have isn't discussed. Genetic determinism is the sexy deus-ex-machina of the day, but even if these findings are correct, one in six couples with no 334 alleles to get in the way still won’t be in fairy-tale land, and two out of three with the 334 allele will still finish each others’ duet.

I’ll give these guys the last word, since they did temper their findings:
The relatively small effect size of the AVPR1A polymorphism on traits tentatively reflecting pair-bonding in males observed in this study clearly does not mean that this polymorphism may serve as a predictor of human pair-bonding behavior on the individual level. However, by demonstrating a modest but significant influence of this gene on the studied behavior on the group level, we have provided support for the assumption that previous studies on the influence of the gene coding for V1aR on pair-bonding in voles are probably of relevance also for humans.

Walum, H., et al., Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans. Proceedings of the National Academy of Sciences, 2008. The article is open access at PNAS.

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