A variation called “CC” in the gene CD38 is associated with increased levels of gratitude


Variation in a specific gene could be related to traits that are beneficial to bonding and relationship satisfaction in the first years of a marriage, according to a new study by a University of Arkansas psychologist.

Recent research indicates that a variation called “CC” in the gene CD38 is associated with increased levels of gratitude. Extending that line of work, U of A psychologist Anastasia Makhanova and her colleagues used data from a study of genotyped newlyweds to explore whether a correlation existed between the CD38 CC variation and levels of trust, forgiveness and marriage satisfaction.

They found that individuals with the CC variation did report higher levels of perceptions considered beneficial to successful relationships, particularly trust.

Marriage satisfaction tends to start high then drop, said Makhanova, assistant professor of psychology and first author of the study, published in the journal Nature Scientific Reports. “We were interested in seeing if some of the reasons that people might have a harder time maintaining relationship satisfaction in the newlywed period is due to some potential underlying genetic predispositions.”

For the work, researchers studied 142 newlyweds – 71 couples – a subset of a larger group used for other studies. The newlyweds’ DNA was collected three months after being married, and they also completed a survey at that point as well as one every four months for three years.

At the end of the study, researchers compared survey results with the CD38 variations and found that those with the specific CC variation reported higher levels of traits corresponding to marriage satisfaction.

“CC individuals felt more grateful for their partner, reported higher trust in their partner, were more forgiving of their partner, and were more satisfied with their marriages than were AC/AA individuals,” the researchers wrote.

While the work points to a possible genetic link to marriage satisfaction, Makhanova notes that it doesn’t mean those without the CD38 CC variation will not have successful relationships.

“So it’s not that people who don’t have the CC genotype are doomed to have problems,” she said. “It’s just that they’re more likely to have issues in some of these domains, and so those people might have to work a little bit more in those domains.”

Satisfying romantic relationships play a critical role in helping people reach important goals, such as those relevant to career, social life, and health1–5. Perhaps most notably, several meta-analyses demonstrate that satisfying relationships are reliable predictors of better mental and physical health4,5, an effect that is at least as powerful as other notable predictors of health, such as physical activity and quitting smoking3.

Although several mechanisms likely explain this association6, many appear to stem directly from high levels of relationship satisfaction7. But unfortunately, remaining satisfied in a long-term romantic relationship is notoriously difficult. Not only do divorce rates in numerous industrialized countries hover between 30 and 50%8,9, relationship satisfaction typically declines even in the relationships that remain intact [e.g.,10].

That said, there is substantial variability in the extent to which people remain satisfied over time [e.g.,11], with some people remaining quite satisfied. Given the implications of relationship satisfaction for health and well-being, understanding the factors that determine whether people remain satisfied, or become dissatisfied, may have important practical implications.

Critically, many challenges couples face over the course of their marriage are often present from the beginning12–14, which is consistent with research suggesting that some marital difficulties stem from stable individual difference factors15,16.

In the current research, we focused on one genetic source of individual differences—individual variation on the CD38 gene (CD38), a gene that has been linked to social cognition and behavior in rodents17, and to positive outcomes in human romantic relationships18,19. Specifically, we sought to test whether CD38 is associated with cognitions and perceptions that help couples strengthen their pair-bond during the challenging newlywed period.

Considerable research, primarily with rodents, has revealed important insights into the biological processes underpinning the maintenance of pair-bonds. Beginning with seminal work on monogamous prairie voles20–22, several decades of research have illuminated the importance of the oxytocin system in pair-bonding behavior in non-human animals23–26.

Notably, recent research has built on this work to suggest a role of peripheral oxytocin levels, and exogenous administration of oxytocin, in attraction and pair-bonding processes in humans [27–32; c.f.33], as well as in more general processes relevant to social relationships such as trust34, perception of others’ emotions35–37, cooperative communication38, and coping with stress32.

In addition to suggesting that peripheral oxytocin levels and exogenous oxytocin administration play a role in human social behavior, research also suggests that genetic differences relating to the oxytocin system play a role in human social behavior. For example, variations in the oxytocin receptor gene (OXTR), such as on the polymorphism rs53576, are linked to supportive communication with one’s romantic partner39, and marital satisfaction in a sample of adults over 5040.

Notwithstanding these two studies, recent meta-analyses disagree on whether rs53576 is linked to human sociality generally41–43, with evidence for a link between OXTR variation and bonding within close relationships being particularly inconsistent43.

More recently, however, a different gene – CD38 – has been implicated in the regulation of oxytocin release and social relationship processes17,44,45. CD38 codes for the transmembrane glycoprotein CD38, which has numerous functions throughout the body. Preliminary evidence suggests that one such function is the modulation of oxytocin release17.

Specifically, CD38 knockout mice (vs. wild-type mice) demonstrated lower plasma oxytocin levels, which, in turn, led to deficits in social cognition and in maternal behavior17. Consistent with the non-human animal work, recent studies in humans also support the link between CD38 and adaptive cognitive and behavioral interpersonal processes18,19,46,47.

These studies have primarily focused on a single-nucleotide polymorphism (SNP), rs3796863, of either an adenine (A) or cytosine (C) located within an intron. For example, one study revealed that young adults with the CC genotype perceived more support from their peers than those with the AC/AA genotypes46. In another study, young adults with the CC genotype reported reduced feelings of alienation from their peers and lower rates of suicidal ideation than those with the AA genotype47.

More directly relevant to the present research, two studies have linked genetic variation in rs3796863 and pair-bonding processes in romantic relationships. One study demonstrated that, compared to those with the AC/AA genotypes, people with the CC genotype, who were in romantic relationships lasting at least 6 months, expressed more gratitude towards their partner, and had more positive responses to their partners’ expressions of gratitude18.

Gratitude appears to function, at least in part, to maintain intimacy and relationship satisfaction48, at least when it occurs in both members of a close relationship49, which suggests CD38 may ultimately facilitate bonding in humans. Indeed, another study demonstrated that this same CD38 SNP was associated with other relationship maintenance processes.

Specifically, in a study using an intensive repeated measurement method to study couples’ daily behavior, Sadikaj and colleagues19 showed that those with the CC (vs. AC/AA) genotype reported engaging in more communal behaviors (e.g., “I expressed affection with words or gestures”) during their interactions with their partner.

Furthermore, people with the CC genotype (vs. AC/AA genotypes) perceived their partner as more communal during these interactions, experienced less negative affect, felt less insecure, and reported better overall relationship adjustment. Taken together, these studies suggest that rs3796863 may play an important role in promoting pair bonding and intimacy through a variety of relationship maintenance processes.

Nevertheless, it remains unclear whether the link between rs3796863 and specific relationship bonding processes (e.g., gratitude, communal behavior) translates into higher levels of global relationship satisfaction that are independent of those processes themselves, as well as what other relationship maintenance processes may be involved.

We leveraged data from a longitudinal study of newlywed couples to examine these issues. Specifically, 71 newlyweds (N = 142 people) completed a battery of questionnaires regarding their relationship cognitions, bonding-related problems, non-bonding-related problems, and relationship satisfaction at a baseline assessment (within 3 months of their wedding); both spouses then reported on their marital satisfaction every four months for the next 3 years (see “Methods”).

Participants also provided saliva samples from which we obtained DNA (139 individuals were successfully genotyped). Given the aforementioned research, we focused on variation in rs3796863. It is worth mentioning that Algoe and Way18 also examined another CD38 SNP, rs6449182, which demonstrated stronger links to gratitude measures; however, we chose to focus on rs3796863 because it has been the focus of the majority of studies on human close relationships, and, moreover, one study identified limited variability on rs644918219.

In our data analytic strategy, we sought to conceptually replicate and extend the findings linking the CC genotype to gratitude17. We predicted that individuals with the CC (vs. AC or AA) genotype would report higher levels of gratitude toward their spouse. Further, given evidence that people with the CC genotype demonstrate other processes that serve to promote bonding18,46,47, we investigated the association between rs3796863 and forgiveness50, a related but independent relationship maintenance process, as well as trust, a critical downstream implication of such processes51.

We predicted that CC individuals would report higher trust in their partner, and would be more forgiving of their partner, than their AC or AA counterparts. We also sought to conceptually replicate and extend prior work linking rs3796863 to global relationship adjustment18; in line with that research, we predicted that CC individuals would report greater marital satisfaction than their AA/AC counterparts.

Here, we also tested whether rs3796863 is associated with discrete processes that should contribute to relationship satisfaction—namely, perceptions of problems in domains related to pair-bonding and intimacy (e.g., showing affection, amount of time spent together, sex, trust, communication). We predicted that CC (vs. AC or AA) individuals would report fewer pair-bonding problems, but not, importantly, fewer problems in other domains (e.g., friends, religion, money management, decision-making).

Finally, we investigated whether the variation in rs3796863 predicted longer-term relationship outcomes by examining the trajectories in relationship satisfaction over the first 3 years of marriage. As noted, this is a particularly vulnerable time for couples; as such, this is a rigorous test of the role of CD38 in relationship maintenance.

Of note, in order to make the best use of this data set, we also conducted a number of exploratory analyses to test associations between rs3796863 and other processes relevant to pair-bonding that were included in the questionnaires that newlywed couples completed at the start of marriage, including attachment insecurity, commitment, perceptions of romantic alternatives, and jealousy.

Although we had did not have strong a priori predictions, these exploratory analyses are valuable in at least two ways. First, they provide insight into potential novel associations between rs3796863 and relationship processes not examined in prior studies. Second, even non-significant associations involving these variables may offer insight into the ways that rs3796863 is discriminately associated with relationship functioning.


Taken together, these findings offer new insights into research at the intersection of genetics and romantic relationships. Regarding relationships, these findings offer novel insights into important precursors that may help or hinder newlyweds as they navigate the first few years of marriage. Polymorphisms on the CD38 gene were associated with bonding-relevant cognitions (gratitude, trust, and forgiveness), and overall marital satisfaction over the course of the first 3 years of marriage.

The reported results represent group-level effects that are relatively small in size and are just one potential source of variance in people’s relationship processes and satisfaction over time. Regarding genetics, these findings support existing findings linking CD38 and the SNP rs3796863 to romantic relationship processes.

Indeed, with the addition of our replication study to the existing literature18,19, there are now three independent samples, by three different research teams, that provide consistent evidence linking the CC genotype (compared to the AC/AA genotypes) to positive romantic relationship cognitions and outcomes.

reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859203/

More information: Anastasia Makhanova et al. CD38 is associated with bonding-relevant cognitions and relationship satisfaction over the first 3 years of marriage, Scientific Reports (2021). DOI: 10.1038/s41598-021-82307-z


Please enter your comment!
Please enter your name here

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.