Father absence, age at menarche, and sexual behaviors in women: Evaluating the genetic confounding hypothesis using the androgen receptor gene.

Abstract

Life history theory posits father absence and associated stressors are key for regulating the development of reproductive phenotypes. The causal status of father absence has been questioned, however, because genetic confounding can account for this association. The purpose of the current study was to replicate and extend prior work that evaluated the androgen receptor gene’s (AR) contribution to the interrelations between father absence and daughters’ age at menarche (AAM) and sexual behaviors by evaluating the GGC, as well as the better characterized CAG polymorphisms. Using structural models on a sample of 269 Caucasian women, we found no evidence to support the genetic confounding hypothesis, though a main effect of CAG variation on earlier AAM was detected independent of father absence. In addition, we tested the hypothesis that associations between father absence and daughter’s sexual behaviors would be mediated by AAM and that indirect effects of father absence would be conditioned by AR variation. Results showed AR variation moderated the association between father absence and AAM and the indirect effects of father absence on daughter’s sexual behaviors, most strongly by the CAG repeat. Implications of these results are discussed in terms of genetic contributions to life history phenotypes and importance of examining gene–environment transactions.

Assessing Effects of Life History Antecedents on Age at Menarche and Sexual Debut Using a Genetically Informative Design

“…Moreover, the non-significant effect of shared environmental factors (i.e., C) suggests that not only did father absence and other measured environmental factors play no significant role in menarche timing; no unmeasured factors that varied between families played such a role either. Also consistent with this conclusion are findings from studies using candidate gene (Schlomer et al, 2019) and polygenetic score (Gaydosh et al, 2018) approaches, which have not supported the genetic confounding hypothesis. A more conclusive test of the genetic confounding hypothesis in future research should use a higher-powered twin study or Genome Wide Association Study (GWAS) to provide more accurate genetic correlation estimates between father absence and menarche timing variables, which could then be used to directly test the simulation-model predictions presented by Barbaro et al (2017).…”

“…Results of investigations attempting to parse out genetic influences to assess the robustness of effects of life history antecedents on menarche timing are mixed and use varying designs. Some investigations have shown no effect of father absence on menarche once genetic variation is accounted for (D'Onofrio et al 2006;Mendle et al, 2006), whereas other investigations have not found evidence to support the genetic confounding hypothesis using sibling (Tither & Ellis, 2008), candidate gene (Schlomer et al, 2019) or polygenic score approaches (Gaydosh et al, 2018). Each of these investigations, however, include only a narrow set of environmental or genetic variables.…”

Meta-Analysis of Direct and Indirect Effects of Father Absence on Menarcheal Timing

“…Compared with extensive evidence that father absence predicts early menarche, no known studies have systematically reviewed and synthesized the mediating effect of childhood stress to account for the father absence effects on early menarche. Previous studies have reported that girls raised in the absence of their fathers are more likely to reach sexual maturation at a younger age (Ellis et al, 2003 ; Anderson, 2015 ; Hehman and Salmon, 2018 ) because the link between father absence and earlier physical maturation is a part of the fast LH strategy (Belsky, 2012 ; Schlomer et al, 2019 ). In addition to the total effect of father absence on earlier onset of menarche, the present study showed that father absence and associated stressors, such as familial perturbation and harsh family environment, also affected physical development.…”

Father absence, age at menarche, and genetic confounding: A replication and extension using a polygenic score

“…This finding was not replicated, however, in a pair of independent follow-up studies (Jorm, Christensen, Rodgers, Jacomb, & Easteal, 2004;Schlomer, Murray, Yates, Hair, & Vandenbergh, 2019). Notably, a bettercharacterized CAG variant within AR was related to earlier AAM independent of father absence and moderated the association between father absence and women's sexual behaviors (Schlomer et al, 2019). Although not specific to father absence, two additional primary and replication studies found that variation in the estrogen receptor-α gene (ESR1) moderated the effect of family relationships on AAM (Hartman, Widaman, & Belsky, 2015;Manuck, Craig, Flory, Halder, & Ferrell, 2011).…”

“…An initial study on father absence and AAM found support for the androgen receptor (AR) genetic confounding hypothesis when examining the GGC variant (Comings, Muhleman, Johnson, & MacMurray, 2002). This finding was not replicated, however, in a pair of independent follow-up studies (Jorm, Christensen, Rodgers, Jacomb, & Easteal, 2004;Schlomer, Murray, Yates, Hair, & Vandenbergh, 2019). Notably, a bettercharacterized CAG variant within AR was related to earlier AAM independent of father absence and moderated the association between father absence and women's sexual behaviors (Schlomer et al, 2019).…”