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Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y - PubMed

  • ️Mon Jan 01 2018

Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y

Anthony F Bogaert et al. Proc Natl Acad Sci U S A. 2018.

Erratum in

Abstract

We conducted a direct test of an immunological explanation of the finding that gay men have a greater number of older brothers than do heterosexual men. This explanation posits that some mothers develop antibodies against a Y-linked protein important in male brain development, and that this effect becomes increasingly likely with each male gestation, altering brain structures underlying sexual orientation in their later-born sons. Immune assays targeting two Y-linked proteins important in brain development-protocadherin 11 Y-linked (PCDH11Y) and neuroligin 4 Y-linked (NLGN4Y; isoforms 1 and 2)-were developed. Plasma from mothers of sons, about half of whom had a gay son, along with additional controls (women with no sons, men) was analyzed for male protein-specific antibodies. Results indicated women had significantly higher anti-NLGN4Y levels than men. In addition, after statistically controlling for number of pregnancies, mothers of gay sons, particularly those with older brothers, had significantly higher anti-NLGN4Y levels than did the control samples of women, including mothers of heterosexual sons. The results suggest an association between a maternal immune response to NLGN4Y and subsequent sexual orientation in male offspring.

Keywords: NLGN4Y; fraternal birth order; homosexuality; maternal immune hypothesis; sexual orientation.

Copyright © 2018 the Author(s). Published by PNAS.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.

Mean rank of antibody concentrations (from lowest, 1, to highest, 154) for PCDH11Y and NLGN4Y by group (women vs. men; n = 154). Error bars represent SEM. (A) Mean rank of antibody concentrations for PCDH11Y by group (Mann–Whitney U = 824.50, P = 0.855, r = −0.02, two-tailed). (B) Mean rank of antibody concentrations for NLGN4Y isoform 1 by group (Mann–Whitney U = 461, P = 0.007, r = −0.21, two-tailed). (C) Mean rank of antibody concentrations for NLGN4Y isoform 2 by group and corrected for batch effects (Mann–Whitney U = 460, P = 0.007, r = −0.21, two-tailed). (D) Mean rank of antibody concentrations for combined NLGN4Y by group (Mann–Whitney U = 420, P = 0.003, r = −0.23, two-tailed).

Fig. 2.
Fig. 2.

Mean rank of antibody concentrations (from lowest, 1, to highest, 142) for NLGN4Y isoform 1 by group controlling for pregnancy (n = 142). Omnibus standardized test statistic from the Jonckheere–Terpstra test = 3.90, P = 0.000096, two-tailed, r = 0.33. Pairwise comparisons: ****P = 0.00035, r = 0.35; ***P = 0.008, r = 0.39; **P = 0.021, r = 0.30; *P = 0.024, r = 0.19. All Ps for pair-wise comparisons are one-tailed. Error bars represent SEM.

Fig. 3.
Fig. 3.

Representation of interaction between the extracellular region of NLGN4Y and neurexin. (A) Typical interaction (27); (B) hypothesized alteration to the typical interaction, caused by antibody binding with NLGN4Y.

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References

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