Population Genetics
Part 5

An examination of the origin and frequency of HD

What is the frequency of HD around the world?

Huntington’s disease is currently found in many different countries and ethnic groups around the world. The highest frequencies of HD are found in Europe and countries of European origin, such as the United States and Australia. The lowest documented frequencies of HD are found in Africa, China, Japan, and Finland.

Though it has been suggested that the frequency of HD is probably low among people of African origin, documentation remains poor and evidence is inconclusive. From the few known cases, however, it has been hypothesized that the HD mutation in Africa has a separate origin from the mutation in Europe or Japan.

• There is a substantial frequency of HD in the white and mixed-race populations of South Africa. Most of the families with HD have Dutch or British ancestry, which suggests that they inherited the European HD allele.
• A 1987 study revealed the HD prevalence among South African blacks to be very low – around 0.6 cases per million people.

While there have not been a lot of studies conducted in Asia, it is thought that HD may be relatively frequent in India, Turkey, and Central Asia. However, HD is relatively rare in China and Japan.

• In Hong Kong, the prevalence of HD between 1984 and 1991 was found to be 3.7 cases per million people. Since the ancestors of these families with HD can be connected to coastal provinces with histories of strong colonial presence, it has been proposed that these cases have a European origin.

• HD is notably rare in Japan, with a prevalence of 1-4 cases per million people – about one-tenth of the prevalence in most European and European-origin populations.
• It has been hypothesized that the HD mutation in Japan has a separate origin from the HD mutation in Europe or Africa.

Europe has a relatively high prevalence of HD in its population, with 40 to 100 cases per million people. The prevalence is rather uniform across almost all of Europe, except for Finland. The geographically even distribution of HD suggests that there has either been:

1. one very ancient mutation responsible for all of the HD cases in Europe, or
2. multiple, separate mutations responsible for the HD cases spread throughout Europe.

Recent studies suggest that multiple, separate mutations are more likely to explain Europe’s uniform HD prevalence rates. For example, a 1994 study suggested at least three origins of the HD allele in Sweden alone. Population geneticists also think that recurring mutations may be necessary to maintain the prevalence of HD at its relatively high level.

• Finland has always been recognized as having a genetically distinct population from the rest of Europe. Therefore, it is not surprising that the prevalence of HD in Finland (at six cases per million people) is drastically different – an order of magnitude less, in fact – than the rest of Europe. This remarkably lower prevalence rate suggests that the Finnish population must have diverged from the European stock before the HD mutation occurred and became widespread in Europe.
• Most, if not all, cases of HD in Finland can be traced to foreign connections. For example, the Aland archipelago near Sweden, which has an unusually high frequency of HD, has been exposed to other populations, including the British, for centuries. Also, a high percentage of Finnish families with HD had foreign ancestors or had Finnish ancestors that lived in border or trade regions.

• A 1994 study in Sweden discovered 10 different variants or haplotypes of the HD allele. However, one of the ten haplotypes accounted for 89% of the families with HD, suggesting that the majority of Swedish families with HD are related through a single HD mutation in their ancestors. This study also suggested at least three origins of the HD mutation in Sweden alone.

• Studies in the UK have shown a high and relatively uniform prevalence of HD across the nation, with no obvious correlation with ethnic origin (Celtic, etc.)
• A 1981 study in South Wales found a prevalence of 76.1 HD cases per million people.
• A 1989 study in the Grampian region of NW Scotland revealed an unusually high HD prevalence of 99.4 cases per million people.
• In Northern Ireland (population 1.5 million), a 1994 study determined an HD prevalence of 64 cases per million people.
• Because there is no single “hot spot” of high prevalence, studies have suggested that there is no single origin of HD in the UK.

Most analysts agree that migration out of Europe has brought HD to North and South America, Australia, New Zealand, and other regions with European contact. The prevalence of HD in these regions is similar to that of Europe (40-100 cases per million people). HD patients in these areas have a wide range of European ethnic origins or contacts, suggesting that there were multiple introductions of the HD allele into these communities in all but the smallest and most isolated groups.

• Among the Caucasian populations of Australia and New Zealand, which include many people of southern ancestry, there is a uniform, widespread distribution of HD.
• Tasmania represents an exception to the uniform distribution of HD throughout Australia. In Tasmania, there is an unusually high frequency of HD in one large clan of English origin. These people are descendents of a single ancestor with HD from Somerset, England.
• There have been no documented cases of HD in the native populations of Australia or New Zealand. Reported occurrences of HD in the Aborigines have a European origin.

• At first glance, HD cases appeared to predate any European settlement. However, it has been suggested that the HD allele was introduced by crews of visiting whaling ships from North America in the first half of the 19th century.

• HD is widespread in most South American countries.
• The largest and best-studied concentration of HD is in Lake Maracaibo, Venezuela. This small community has over 100 living individuals with HD, all of whom are descendents from a single ancestor, probably of European origin. Studies in Lake Maracaibo have helped to localize the HD gene and document the etiology of HD. (To learn more about Lake Maracaibo, click here.)
• There have been no documented cases of HD in the native populations of South America.

• As of the year 2000, there were 30,000 cases of HD in the United States – indicating a prevalence rate of about 100 cases per million people.
• Among the European-American population, there is a uniform distribution across the United States. The ethnic origins of these families with HD can be traced to a variety of European countries.
• A 1987 study determined the prevalence of HD in African Americans to be 15 cases per million people – much lower than the prevalence in European Americans. In most of these affected families, the HD allele did not have a European origin.
• There have been no documented cases of HD among the Native American populations of North America.

Last Modified: 04/12/2007

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