The study, published in Science, used data from the UK Biobank and 23andMe, and found some genetic variants associated with same-sex relationships.
But genetic factors accounted for, at most, 25% of same-sex behaviour.
Advocacy group GLAAD said the study confirmed "no conclusive degree to which nature or nurture influenced how a gay or lesbian person behaves."
The researchers scanned the genomes - the entire genetic make-up - of 409,000 people signed up to the UK Biobank project, and 68,500 registered with the genetics company 23andMe.
Participants were also asked whether they had same-sex partners exclusively, or as well as opposite-sex partners.
The Harvard and MIT researchers concluded genetics could account for between 8-25% of same-sex behaviour across the population, when the whole genome is considered.
Five specific genetic variants were found to be particularly associated with same-sex behaviour, including one linked to the biological pathway for smell, and others to those for sex hormones.
But together they only accounted for under 1% of same-sex behaviour.
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