Biology and sexual orientation

The relationship between biology and sexual orientation is a subject of research. A simple and singular determinant for sexual orientation has not been conclusively demonstrated—various studies point to different, even conflicting positions—but scientists hypothesize that a combination of genetic, hormonal and social factors determine sexual orientation. Biological theories for explaining the causes of sexual orientation are more popular, and biological factors may involve a complex interplay of genetic factors and the early uterine environment. These factors, which may be related to the development of a heterosexual, homosexual, bisexual or asexual orientation, include genes, prenatal hormones, and brain structure.

Twin studies
A number of twin studies have attempted to compare the relative importance of genetics and environment in the determination of sexual orientation. In a 1991 study, Bailey and Pillard found that 52% of monozygotic (MZ) brothers and 22% of the dizygotic (DZ) twins were concordant for homosexuality. 'MZ' indicates identical twins with the same sets of genes and 'DZ' indicates fraternal twins where genes are mixed to a similar extent as non-twin siblings. In 2000, Bailey, Dunne and Martin found similar results from a larger sample of 4,901 Australian twins. Self reported zygosity, sexual attraction, fantasy and behaviours were assessed by questionnaire and zygosity was serologically checked when in doubt. They found 20% concordance in the male identical or MZ twins and 24% concordance for the female identical or MZ twins. A meta-study by Hershberger (2001) compares the results of eight different twin studies: among those, all but two showed MZ twins having much higher concordance of sexual orientation than DZ twins, suggesting a non-negligible genetic component.

Bearman and Brückner (2002) criticized early studies of concentrating on small, select samples and non-representative selection of their subjects. They studied 289 pairs of identical twins (monozygotic or from one fertilized egg) and 495 pairs of fraternal twins (dizygotic or from two fertilized eggs) and found concordance rates for same-sex attraction of only 7.7% for male identical twins and 5.3% for females, a pattern which they say "does not suggest genetic influence independent of social context."

A 2010 study of all adult twins in Sweden (more than 7,600 twins) found that same-sex behavior was explained by both heritable factors and individual-specific environmental sources (such as prenatal environment, experience with illness and trauma, as well as peer groups, and sexual experiences), while influences of shared-environment variables such as familial environment and societal attitudes had a weaker, but significant effect. Women showed a statistically non-significant trend to weaker influence of hereditary effects, while men showed no effect of shared environmental effects. The use of all adult twins in Sweden was designed to address the criticism of volunteer studies, in which a potential bias towards participation by gay twins may influence the results;

Criticisms
Twin studies have received a number of criticisms including self-selection bias where homosexuals with gay siblings are more likely to volunteer for studies. Nonetheless, it is possible to conclude that, given the difference in sexuality in so many sets of identical twins, sexual orientation cannot be attributed solely to genetic factors.

Another issue is the recent finding that even monozygotic twins can be different and there is a mechanism which might account for monozygotic twins being discordant for homosexuality. Gringas and Chen (2001) describe a number of mechanisms which can lead to differences between monozygotic twins, the most relevant here being chorionicity and amniocity. Dichorionic twins potentially have different hormonal environments because they receive maternal blood from separate placenta, and this could result in different levels of brain masculinisation. Monoamniotic twins share a hormonal environment, but can suffer from the 'twin to twin transfusion syndrome' in which one twin is "relatively stuffed with blood and the other exsanguinated".

Chromosome linkage studies
Chromosome linkage studies of sexual orientation have indicated the presence of multiple contributing genetic factors throughout the genome. In 1993, Dean Hamer and colleagues published findings from a linkage analysis of a sample of 76 gay brothers and their families. Hamer et al. found that the gay men had more gay male uncles and cousins on the maternal side of the family than on the paternal side. Gay brothers who showed this maternal pedigree were then tested for X chromosome linkage, using twenty-two markers on the X chromosome to test for similar alleles. In another finding, thirty-three of the forty sibling pairs tested were found to have similar alleles in the distal region of Xq28, which was significantly higher than the expected rates of 50% for fraternal brothers. This was popularly dubbed as the "gay gene" in the media, causing significant controversy. Sanders et al. in 1998 reported on their similar study, in which they found that 13% of uncles of gay brothers on the maternal side were homosexual, compared to 6% on the paternal side.

A later analysis by Hu et al. replicated and refined the earlier findings. This study revealed that 67% of gay brothers in a new saturated sample shared a marker on the X chromosome at Xq28. Although two other studies (Bailey et al., 1999; McKnight and Malcolm, 2000) failed to find a preponderance of gay relatives in the maternal line of homosexual men, One study by Rice et al. in 1999 failed to replicate the Xq28 linkage results. Meta-analysis of all available linkage data indicates a significant link to Xq28, but also indicates that additional genes must be present to account for the full heritability of sexual orientation. A recent study of 894 heterosexual and 694 homosexual men found no evidence of sex linkage.

Mustanski et al. (2005) performed a full-genome scan (instead of just an X chromosome scan) on individuals and families previously reported on in Hamer et al. (1993) and Hu et al. (1995), as well as additional new subjects. With the larger sample set and complete genome scan, the study found somewhat reduced linkage for Xq28 than reported by Hamer et al. However, they did find other markers with a likelihood score falling just short of significance at 7q36 and likelihood scores approaching significance at 8p12 and 10q26. Interestingly, 10q26 showed highly significant maternal loading, thus further supporting the previous family studies.

In July 2010 a group of geneticists at the Korea Advanced Institute of Science an Technology altered the sexual preferences of female mice by removing a single gene linked to reproductive behavior. Without the gene, the mice exhibited masculine sexual behavior and attraction toward urine of other female mice. Those mice who retained the gene fucose mutarotase (FucM) were attracted to male mice.

Epigenetics studies
A study suggests linkage between a mother's genetic make-up and homosexuality of her sons. Women have two X chromosomes, one of which is "switched off". The inactivation of the X chromosome occurs randomly throughout the embryo, resulting in cells that are mosaic with respect to which chromosome is active. In some cases though, it appears that this switching off can occur in a non-random fashion. Bocklandt et al. (2006) reported that, in mothers of homosexual men, the number of women with extreme skewing of X chromosome inactivation is significantly higher than in mothers without gay sons. Thirteen percent of mothers with one gay son, and 23% of mothers with two gay sons showed extreme skewing, compared to 4% percent of mothers without gay sons.

Birth order
Blanchard and Klassen (1997) reported that each older brother increases the odds of a man being gay by 33%. This is now "one of the most reliable epidemiological variables ever identified in the study of sexual orientation." To explain this finding, it has been proposed that male fetuses provoke a maternal immune reaction that becomes stronger with each successive male fetus. This maternal immunization hypothesis (MIH) begins when cells from a male fetus enter the mother's circulation during pregnancy or while giving birth. Male fetuses produce HY antigens which are "almost certainly involved in the sexual differentiation of vertebrates." These Y-linked proteins would not be recognized in the mother's immune system because she is female, causing her to develop antibodies which would travel through the placental barrier into the fetal compartment. From here, the anti-male bodies would then cross the blood/brain barrier (BBB) of the developing fetal brain, altering sex-dimorphic brain structures relative to sexual orientation, increasing the likelihood that the exposed son will be more attracted to men than women. It is this antigen which maternal H-Y antibodies are proposed to both react to and 'remember'. Successive male fetuses are then attacked by H-Y antibodies which somehow decrease the ability of H-Y antigens to perform their usual function in brain masculinisation. However the theory has been criticized because symptoms which would be typical of such effects are rare compared with the prevalence of homosexuality.

Female fertility
In 2004, Italian researchers conducted a study of about 4,600 people who were the relatives of 98 homosexual and 100 heterosexual men. Female relatives of the homosexual men tended to have more offspring than those of the heterosexual men. Female relatives of the homosexual men on their mother's side tended to have more offspring than those on the father's side. The researchers concluded that there was genetic material being passed down on the X chromosome which both promotes fertility in the mother and homosexuality in her male offspring. The connections discovered would explain about 20% of the cases studied, indicating that this is a highly significant but not the sole genetic factor determining sexual orientation.

Pheromone studies
Research conducted in Sweden has suggested that gay and straight men respond differently to two odors that are believed to be involved in sexual arousal. The research showed that when both heterosexual women (lesbians were included in the study, but the results regarding them were "somewhat confused") and gay men are exposed to a testosterone derivative found in men's sweat, a region in the hypothalamus is activated. Heterosexual men, on the other hand, have a similar response to an estrogen-like compound found in women's urine. The conclusion is that sexual attraction, whether same-sex or opposite-sex oriented, operates similarly on a biological level. Researchers have suggested that this possibility could be further explored by studying young subjects to see if similar responses in the hypothalamus are found and then correlating these data with adult sexual orientation.

Studies of brain structure
A number of sections of the brain have been reported to be sexually dimorphic; that is, they vary between men and women. There have also been reports of variations in brain structure corresponding to sexual orientation. In 1990, Dick Swaab and Hofman reported a difference in the size of the suprachiasmatic nucleus between homosexual and heterosexual men. In 1992, Allen and Gorski reported a difference related to sexual orientation in the size of the anterior commissure.

Sexually dimorphic nuclei in the anterior hypothalamus
Simon LeVay, too, conducted some of these early researches. He studied four groups of neurons in the hypothalamus called INAH1, INAH2, INAH3 and INAH4. This was a relevant area of the brain to study, because of evidence that it played a role in the regulation of sexual behaviour in animals, and because INAH2 and INAH3 had previously been reported to differ in size between men and women.

He obtained brains from 41 deceased hospital patients. The subjects were classified into three groups. The first group comprised 19 gay men who had died of AIDS-related illnesses. The second group comprised 16 men whose sexual orientation was unknown, but whom the researchers presumed to be heterosexual. Six of these men had died of AIDS-related illnesses. The third group was of six women whom the researchers presumed to be heterosexual. One of the women had died of an AIDS-related illness.

The HIV-positive people in the presumably heterosexual patient groups were all identified from medical records as either intravenous drug abusers or recipients of blood transfusions. Two of the men who identified as heterosexual specifically denied ever engaging in a homosexual sex act. The records of the remaining heterosexual subjects contained no information about their sexual orientation; they were assumed to have been primarily or exclusively heterosexual "on the basis of the numerical preponderance of heterosexual men in the population."

LeVay found no evidence for a difference between the groups in the size of INAH1, INAH2 or INAH4. However, the INAH3 group appeared to be twice as big in the heterosexual male group as in the gay male group; the difference was highly significant, and remained significant when only the six AIDS patients were included in the heterosexual group. The size of INAH3 in the homosexual men's brains was comparable to the size of INAH3 in the heterosexual women's brains.

William Byne and colleagues attempted to identify the size differences reported in INAH 1-4 by replicating the experiment using brain sample from other subjects: 14 HIV-positive homosexual males, 34 presumed heterosexual males (10 HIV-positive), and 34 presumed heterosexual females (9 HIV-positive). The researchers found a significant difference in INAH3 size between heterosexual men and heterosexual women. The INAH3 size of the homosexual men was apparently smaller than that of the heterosexual men, and larger than that of the heterosexual women, though neither difference quite reached statistical significance.

Byne and colleagues also weighed and counted numbers of neurons in INAH3 tests not carried out by LeVay. The results for INAH3 weight were similar to those for INAH3 size; that is, the INAH3 weight for the heterosexual male brains was significantly larger than for the heterosexual female brains, while the results for the gay male group were between those of the other two groups but not quite significantly different from either. The neuron count also found a male-female difference in INAH3, but found no trend related to sexual orientation.

A 2010 study, Garcia-Falgueras and Swaab asserted that "the fetal brain develops during the intrauterine period in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge. In this way, our gender identity (the conviction of belonging to the male or female gender) and sexual orientation are programmed or organized into our brain structures when we are still in the womb. There is no indication that social environment after birth has an effect on gender identity or sexual orientation."

The ovine model
The domestic ram is used as an experimental model to study early programming of the neural mechanisms which underlie homosexuality, developing from the observation that approximately 8% of domestic rams are sexually attracted to other rams (male-oriented) when compared to the majority of rams which are female-oriented. In many species, a prominent feature of sexual differentiation is the presence of a sexually dimorphic nucleus (SDN) in the preoptic hypothalamus, which is larger in males than in females.

Roselli et al. discovered an ovine SDN (oSDN) in the preoptic hypothalamus that is smaller in male-oriented rams than in female-oriented rams, but similar in size to the oSDN of females. Neurons of the oSDN show aromatase expression which is also smaller in male-oriented rams versus female-oriented rams, suggesting that sexual orientation is neurologically hard-wired and may be influenced by hormones. However, results failed to associate the role of neural aromatase in the sexual differentiation of brain and behavior in the sheep, due to the lack of defeminization of adult sexual partner preference or oSDN volume as a result of aromatase activity in the brain of the fetuses during the critical period. Having said this, it is more likely that oSDN morphology and homosexuality may be programmed through an androgen receptor that does not involve aromatisation. Most of the data suggests that homosexual rams, like female-oriented rams, are masculinized and defeminized with respect to mounting, receptivity, and gonadotrophin secretion, but are not defeminized for sexual partner preferences, also suggesting that such behaviors may be programmed differently. Although the exact function of the oSDN is not fully known, its volume, length, and cell number seem to correlate with sexual orientation, and a dimorphism in its volume and of cells could bias the processing cues involved in partner selection. More research is needed in order to understand the requirements and timing of the development of the oSDN and how prenatal programming effects the expression of mate choice in adulthood.

Early fixation hypothesis
The early fixation hypothesis includes research into prenatal development and the environmental factors that control masculinization of the brain. Some studies have seen pre-natal hormone exposures as the primary factor involved in determining sexual orientation. This hypothesis is supported by both the observed differences in brain structure and cognitive processing between homosexual and heterosexual men. One explanation for these differences is the idea that differential exposure to hormone levels in the womb during fetal development may change the masculinization of the brain in homosexual men. The concentrations of these chemicals is thought to be influenced by fetal and maternal immune systems, maternal consumption of certain drugs, maternal stress, and direct injection. This hypothesis is also connected to the fraternal birth order research.

Exotic becomes erotic
Daryl Bem, a social psychologist at Cornell University, has theorized that the influence of biological factors on sexual orientation may be mediated by experiences in childhood. A child's temperament predisposes the child to prefer certain activities over others. Because of their temperament, which is influenced by biological variables such as genetic factors, some children will be attracted to activities that are commonly enjoyed by other children of the same gender. Others will prefer activities that are typical of another gender. This will make a gender-conforming child feel different from opposite-gender children, while gender-nonconforming children will feel different from children of their own gender. According to Bem, this feeling of difference will evoke psychological arousal when the child is near members of the gender which it considers as being 'different'. Bem theorizes that this psychological arousal will later be transformed into sexual arousal: children will become sexually attracted to the gender which they see as different ("exotic"). This theory is known as Exotic Becomes Erotic theory.

The theory is based in part on the frequent finding that a majority of gay men and lesbians report being gender-nonconforming during their childhood years. A meta-analysis of 48 studies showed childhood gender nonconformity to be the strongest predictor of a homosexual orientation for both men and women. Fourteen studies published since Bailey & Zucker's 1995 also show the same results. In one study by the Kinsey Institute of approximately 1000 gay men and lesbians (and a control group of 500 heterosexual men and women), 63% of both gay men and lesbians reported that they were gender nonconforming in childhood (i.e., did not like activities typical of their sex), compared with only 10–15% of heterosexual men and women. There are also six "prospective" studies—that is longitudinal studies that begin with gender-nonconforming boys at about age 7 and follow them up into adolescence and adulthood. These also show that a majority (63%) of the gender nonconforming boys become gay or bisexual as adults. There are very few prospective studies of gender nonconforming girls. In a group of eighteen behaviorally masculine girls (mean age of assessment: 9 years), all reported a homosexual sexual orientation at adolescence, and eight had requested sex reassignment.

William Reiner, a psychiatrist and urologist with the University of Oklahoma has evaluated more than a hundred cases of children born with sexual differentiation disorders. In the 1960s and '70s, it was common in developed countries for doctors to castrate boys born with a micropenis and have them raised as girls. However, this practice has come under attack, because even though these boys were raised as girls, they nearly all report as adults that they are sexually attracted to women. This suggests that their sexual orientation was determined at birth.

Sexual orientation and evolution
Sexual practices that significantly reduce the frequency of heterosexual intercourse also significantly decrease the chances of successful reproduction, and for this reason, they would appear to be maladaptive in an evolutionary context following a simple Darwinian model of natural selection—on the assumption that homosexuality would reduce this frequency. Several theories have been advanced to explain this contradiction, and new experimental evidence has demonstrated their feasibility.

Some scholars have suggested that homosexuality is adaptive in a non-obvious way. By way of analogy, the allele (a particular version of a gene) which causes sickle-cell anemia when two copies are present may also confer resistance to malaria with a lesser form of anemia when one copy is present (this is called heterozygous advantage).

The so-called "gay uncle" hypothesis posits that people who themselves do not have children may nonetheless increase the prevalence of their family's genes in future generations by providing resources (food, supervision, defense, shelter, etc.) to the offspring of their closest relatives. This hypothesis is an extension of the theory of kin selection. Kin selection was originally developed to explain apparent altruistic acts which seemed to be maladaptive. The initial concept was suggested by J.B.S. Haldane in 1932 and later elaborated by many others including John Maynard Smith, W. D. Hamilton and Mary Jane West-Eberhard. This concept was also used to explain the patterns of certain social insects where most of the members are non-reproductive.

Brendan Zietsch of the Queensland Institute of Medical Research proposes the alternative theory that men exhibiting female traits become more attractive to females and are thus more likely to mate, provided the genes involved do not drive them to complete rejection of heterosexuality.

In a 2008 study, its authors stated that "There is considerable evidence that human sexual orientation is genetically influenced, so it is not known how homosexuality, which tends to lower reproductive success, is maintained in the population at a relatively high frequency." They hypothesized that "while genes predisposing to homosexuality reduce homosexuals' reproductive success, they may confer some advantage in heterosexuals who carry them." and their results suggested that "genes predisposing to homosexuality may confer a mating advantage in heterosexuals, which could help explain the evolution and maintenance of homosexuality in the population.". However, in the same study, the authors noted that "nongenetic alternative explanations cannot be ruled out" as a reason for the heterosexual in the homosexual-heterosexual twin pair having more partners, specifically citing "social pressure on the other twin to act in a more heterosexual way" (and thus seek out a greater number of sexual partners) as an example of one alternative explanation. Also, the authors of the study acknowledge that a large number of sexual partners may not lead to greater reproductive success, specifically noting there is an "absence of evidence relating the number of sexual partners and actual reproductive success,either in the present or in our evolutionary past."

Important new evidence on a plausible mechanism for the evolution of "gay genes" has emerged from the work of Camperio-Ciani. They found in two large, independent studies that the female relatives of homosexual men tended to have significantly more offspring than those of the heterosexual men. Female relatives of the homosexual men on their mother's side tended to have more offspring than those on the father's side. This indicates that females carrying a putative "androphilia genes" complex are more fecund than women lacking this complex of genes, and thereby can compensate for any decreased fertility of the males carrying the genes. This is a well known phenomenon in evolution known as "sexual antagonism," and has been widely documented for many traits that are advantageous in one sex but not in the other. This provides solid experimental evidence of how "gay genes" could not only survive but thrive over the course of evolution.

Physiological
Some studies have found correlations between physiology of people and their sexuality. These studies provide evidence which they claim suggests that:


 * Gay men and straight women have, on average, equally proportioned brain hemispheres. Lesbian women and straight men have, on average, slightly larger right brain hemispheres.
 * The VIP SCN nucleus of the hypothalamus is larger in men than in women, and larger in gay men than in heterosexual men.
 * Gay men report, on an average, slightly longer and thicker penises than non-gay men.
 * The average size of the INAH-3 in the brains of gay men is approximately the same size as INAH 3 in women, which is significantly smaller, and the cells more densely packed, than in heterosexual men's brains.
 * The anterior commissure is larger in women than men and was reported to be larger in gay men than in non-gay men, but a subsequent study found no such difference.
 * Gay men's brains respond differently to fluoxetine, a selective serotonin reuptake inhibitor.
 * The functioning of the inner ear and the central auditory system in lesbians and bisexual women are more like the functional properties found in men than in non-gay women (the researchers argued this finding was consistent with the prenatal hormonal theory of sexual orientation).
 * The suprachiasmatic nucleus was found by Swaab and Hopffman to be larger in gay men than in non-gay men, the suprachiasmatic nucleus is also known to be larger in men than in women.
 * The startle response (eyeblink following a loud sound) is similarly masculinized in lesbians and bisexual women.
 * Gay and non-gay people's brains respond differently to two putative sex pheromones (AND, found in male armpit secretions, and EST, found in female urine).
 * The amygdala, a region of the brain, is more active in gay men than non-gay men when exposed to sexually arousing material.
 * Finger length ratios between the index and ring fingers may be different between non-gay and lesbian women.
 * Gay men and lesbians are significantly more likely to be left-handed or ambidextrous than non-gay men and women;  Simon LeVay argues that because "[h]and preference is observable before birth... [t]he observation of increased non-right-handness in gay people is therefore consistent with the idea that sexual orientation is influenced by prenatal processes," perhaps heredity.
 * A study of over 50 gay men found that about around 23% had counterclockwise hair whorl, as opposed to 8% in the general population. This may correlate with left-handedness.
 * Gay men have increased ridge density in the fingerprints on their left thumbs and pinkies.
 * Length of limbs and hands of gay men is smaller compared to height than the general population, but only among white men.

Cognitive
Recent studies suggest the presence of subtle differences in the way gay people and non-gay people process certain kinds of information. Researchers have found that:
 * Gay men and lesbians are more verbally fluent than heterosexuals of the same sex  (but two studies did not find this result).
 * Gay men may receive higher scores than non-gay men on tests of object location memory (no difference was found between lesbians and non-gay women).

Political aspects
Whether genetic or other physiological determinants form the basis of sexual orientation is a highly politicized issue. The Advocate, a U.S. gay and lesbian newsmagazine, reported in 1996 that 61% of its readers believed that "it would mostly help gay and lesbian rights if homosexuality were found to be biologically determined". A cross-national study in the United States, the Philippines, and Sweden found that those who believed that "homosexuals are born that way" held significantly more positive attitudes toward homosexuality than those who believed that "homosexuals choose to be that way" or "learn to be that way".

Equal protection analysis in U.S. law determines what groups are considered suspect classes and therefore eligible for heightened scrutiny based on several factors, one of which is immutability. Evidence that sexual orientation is biologically determined (and therefore perhaps immutable in the legal sense) would strengthen the legal case for heightened scrutiny of laws discriminating on that basis.

The perceived causes of sexual orientation have a significant bearing on the status of sexual minorities in the eyes of social conservatives. The Family Research Council, a conservative Christian think tank in Washington, D.C., argues in the book Getting It Straight that finding people are born gay "would advance the idea that sexual orientation is an innate characteristic, like race; that homosexuals, like African-Americans, should be legally protected against 'discrimination;' and that disapproval of homosexuality should be as socially stigmatized as racism. However, it is not true.", but did not give any further explanations. On the other hand, some social conservatives such as Reverend Robert Schenck have argued that people can accept the "inevitable... scientific evidence" while still morally opposing homosexuality. As well, National Organization for Marriage board member and fiction writer Orson Scott Card has supported biological research on homosexuality, writing that "our scientific efforts in regard to homosexuality should be to identify genetic and uterine causes... so that the incidence of this dysfunction can be minimized.... [However, this should not be seen] as an attack on homosexuals, a desire to 'commit genocide' against the homosexual community.... There is no 'cure' for homosexuality because it is not a disease. There are, however, different ways of living with homosexual desires."

Some advocates for the rights of sexual minorities resist linking that cause with the concept that sexuality is biologically determined or fixed at birth. They argue that sexual orientation can shift over the course of a person's life. At the same time, others resist any attempts to pathologise or medicalise 'deviant' sexuality, and choose to fight for acceptance in a moral or social realm. Chandler Burr has stated that "[s]ome, recalling earlier psychiatric "treatments" for homosexuality, discern in the biological quest the seeds of genocide. They conjure up the specter of the surgical or chemical "rewiring" of gay people, or of abortions of fetal homosexuals who have been hunted down in the womb." Simon LeVay has said, in response to letters from gays and lesbians making such criticisms, that the research "has contributed to the status of gay people in society."