Spector told the BBC: "It's a mystery and it's intriguing because it wasn't what we were looking for. We thought it was a bias but it wouldn't go away and it's found in every sub-group of every population we saw," he said.
"It's a curious mystery because it's a very big effect - to see two and threefold effects both in a whole variety of American populations and European ones was quite amazing."
The researchers analysed the DNA of almost 300,000 people of European descent from data supplied by UK Biobank, at-home genetic-testing service 23andMe Inc, the International Visible Trait Genetics Consortium and their study partners.
They add their findings could boost treatments in many different diseases, the Daily Mail reports.
Spector added: "This work will impact several fields of biology and medicine.
"As the largest ever genetic study on pigmentation, it will improve our understanding of diseases like melanoma, an aggressive form of skin cancer.
"The genes that affect hair colour also affect other cancer types, while other pigment genes affect the chances of having Crohn's and other forms of bowel disease."
The researchers add their findings could advance scientists' knowledge of other conditions linked to pigmentation, including testicular, prostate and ovarian cancers.
Spector said: "Our work helps us to understand what causes human diversity in appearance by showing how genes involved in pigmentation subtly adapted to external environments and even social interactions during our evolution. "
The findings were published in the journal Nature Genetics.