Warby et al. Supplemental
SUPPLEMENTAL DATA
HTT haplotypes contribute to differences in Huntington disease prevalence between
Europe and East Asia
Simon C. Warby 1 , Henk Visscher 1 , Jennifer A. Collins 1 , Crystal N. Doty 1 , Catherine Carter 1 , Stefanie L.
Butland 1 , Anna R. Hayden 1 , Ichiro Kanazawa 2 , Colin J. Ross 1 , Michael R. Hayden 1
S1

Warby et al. Supplemental
Supplementary Table 1 (Part 1 of 2): Worldwide minimum estimates of HD prevalence (per 100,000).
POPULATION
Australia (New South Wales)
DATE PREVALENCE
1996 6.3
REFERENCE
(McCusker et al 2000)
Australia (Queensland)
Australia (Queensland)
Australia (Tasmania)
Australia (Victoria)
Austria
Azerbaijan
Belgium (Liege, Limbourg, Namur, Luxembourg)
Canada (Manitoba & Saskatchewan)
China (Hong Kong)
China (Hong Kong)
Croatia
Egypt (Assiut)
Finland
France (North-West)
Germany (Kassel)
Germany (Rhineland)
Germany (West, without Berlin & Saarland)
Germany (West, without Berlin & Saarland)
Germany
Guam (Chamorros)
Iceland
India (Pakistan, Punjab and Gujerat)
Italy (Aosta)
Italy (Emilia & Parma)
Italy (Ferrara province)
Italy (Florence)
Italy (Frogiuone)
Italy (Genoa Region)
Italy (Genoa-Savona)
Italy (Latima)
Italy (Lazio)
Italy (Puglia)
Italy (Rieti)
Italy (Rome)
Italy (Tuscany)
Italy (Viterbo)
Japan (Aichi)
Japan (Ibaraki)
Japan (San-in)
Japan (San-in)
Malta
Malta
Mauritius (European descent)
Mexico
New Zealand
Nigeria (Ibadan)
Norway
Norway
Norway
Poland (Pruszkow)
Russia (6 populations in Central Asia)
Russia (Volgograd and Volzhsky)
Russia (Vladimir Oblast)
Slovenia
South Africa
South Africa (Blacks)
1976
1969
1990
1963
1993-1997
1985
1970
1975
1984-1991
1984-1991
2002
1988-1990
1986
2.3
1.5
0.4
0.1
0.7
3.0
2.6
2.9
5.6
2.5
0.0
2.7
1.7
5.0
4.8
1.9
4.1
2.6
28.0
4.5
1.0
21.0
0.5
5.0
2.6
3.2
2.2
2.2
10.0
5.8
6.3
12.1
4.6
10.0
23.8
1.6
8.4
0.4
0.4
4.8
1.3
0.6
1.9
5.2
0.6
0.01
0.7
11.8
7.8
46.2
4.0
5.7
0.2
6.9
6.7
5.8
1950
1933
1950
1939
1993-1997
1967
1963
1990
1982-1991
1980
1987
1970-1979
1981
1930-1977
1973
1981
1981
1980
1981
1981
1978
1981
1959
1982
1993
1997
1994
1977
2008
1930
1940
1950
1960
2006
1979
1979
(Wallace & Parker 1979)
(Wallace & Parker 1973)
(Pridmore 1990)
(Brothers 1964)
(Laccone et al 1999)
(Al-Jader et al 2001)
(Husquinet 1973)
(Shokeir 1975)
(Leung et al 1992)
(Chang et al 1994)
(Hecimovic et al 2002)
(Kandil et al 1994)
(Palo et al 1987)
(Petit & Salomez 1985)
(Al-Jader et al 2001)
(Al-Jader et al 2001)
(Al-Jader et al 2001)
(Al-Jader et al 2001)
(Laccone et al 1999)
(Chen et al 1968)
(Gudmundsson 1969)
(Shiwach & Lindenbaum 1990)
(Al-Jader et al 2001)
(Al-Jader et al 2001)
(Govoni et al 1988)
(Groppi et al 1986)
(Frontali et al 1990)
(Roccatagliata et al 1979)
(Roccatagliata & Albano 1976)
(Frontali et al 1990)
(Frontali et al 1990)
(Al-Jader et al 2001)
(Frontali et al 1990)
(Frontali et al 1990)
(Al-Jader et al 2001)
(Frontali et al 1990)
(Kishimoto et al 1957)
(Kanazawa et al 1990)
(Nakashima et al 1996)
(Adachi & Nakashima 1999)
(Gassivaro Gallo et al 1999)
(Al-Jader et al 2001)
(Hayden et al 1981)
(Alonso et al 2009)
(Harper 1996)
(Aiyesimoju et al 1984)
(Saugstad & Odegård 1986)
(Saugstad & Odegård 1986)
(Saugstad & Odegård 1986)
(Al-Jader et al 2001)
(Kirilenko et al 2004)
(Kirilenko et al 2004)
(Kirilenko et al 2004)
(Peterlin et al 2008)
(Hayden et al 1982)
(Hayden et al 1980)
S2

Warby et al. Supplemental
Supplementary Table 1 (Part 2/2): Worldwide minimum estimates of HD prevalence (per 100,000).
POPULATION
South Africa (Cape Coloured population, mixed race)
DATE PREVALENCE
1976 3.5
REFERENCE
(Hayden & Beighton 1977)
South Africa (Mixed race) 1979 0.9 (Hayden & Beighton 1977)
South Africa (White and Coloured population)
South Africa (Whites Afrikaans)
Spain (Salamanca)
Spain (Cadiz province)
Spain (Valencia)
Sweden
Sweden
Switzerland
Tanzania (Mount Kilimanjaro, Bantu community)
UK (England, Carlisle)
UK (England, Cornwall)
UK (England, Cornwall)
UK (England, Devon)
UK (England, East Anglia)
UK (England, Essex)
UK (England, Leeds)
UK (England, Northamptonshire)
UK (England, Northamptonshire)
UK (England, Northamptonshire)
1979
1979
UK (England, Oxford region)
UK (England, Somerset)
UK (England, Wessex)
UK (Indian subcontinent immigrants)
UK (Ireland, Northern)
UK (Ireland, Northern, County Donegal)
UK (Scotland, Grampian, north-east )
UK (Scotland, South-East)
UK (Scotland, West)
UK (Wales, North)
UK (Wales, South & Glamorgan) 1988
UK (Wales, South Glamorgan, Glamorgan & Gwent) 1994
UK (Wales, South)
UK (Wales, South)
UK (Wales, South)
1981
1971
1971
USA & Australia (Whites)
USA (Blacks)
USA (Maryland)
USA (Maryland, Blacks)
USA (Michigan)
1940
1980
1980
1940
1985
1965
1987
1990
1991
1991
1984
1967
1960
1981
1968
1987-1992
1965
1985
1993-1997
1980
1961
1950
1987
1987
1971
1965
1966
1967-1968
1960
1954-1955
USA (Minnesota)
USA (Minnesota, Olmsted county)
USA (Minnesota, Olmsted county)
USA (Minnesota, Rochester)
USA (New York, Jews)
1955
1990
1960
1955
1973
USA (South Carolina, Blacks)
USA (South Carolina, White)
Venezuela
Venezuela (Lake Maracaibo)
Yugoslavia (Rijeka district)
1980
1980
1973
1981
Zimbabwe (Manicaland region, Shona population) 1988-1989
5.0
1.5
5.2
6.4
4.1
8.4
6.2
8.9
7.6
7.6
5.7
5.5
3.7
1.7
6.4
1.6
10.0
7.2
5.2
5.5
5.4
2.0
6.0
6.7
3.5
1.0
4.8
0.5
699.3
4.5
0.8
5.6
4.9
4.6
9.2
2.5
4.2
6.3
7.2
6.5
2.2
0.4
8.4
1.3
5.4
4.7
5.6
10.0
7.0
2.8
(Hayden et al 1980)
(Hayden & Beighton 1977)
(Ruiz et al 1985)
(Calcedo Ordóñez 1970)
(Burguera et al 1997)
(Mattsson 1974)
(Al-Jader et al 2001)
(Laccone et al 1999)
(Scrimgeour 1981)
(Brewis et al 1966)
(Bickford & Ellison 1953)
(Harper 1996)
(Harper 1996)
(Caro 1977)
(Heathfield 1967)
(Al-Jader et al 2001)
(Oliver 1970)
(Reid 1960)
(Pleydell 1955)
(Shiwach 1994)
(Al-Jader et al 2001)
(Harper 1996)
(Shiwach & Lindenbaum 1990)
(Morrison et al 1995)
(Morrison & Nevin 1993)
(Simpson & Johnston 1989)
(Cameron & Venters 1967)
(Bolt 1970)
(Quarrell et al 1988)
(MacMillan & Harper 1991)
(James et al 1994)
(Quarrell et al 1988)
(Walker et al 1981)
(Harper et al 1979)
(Al-Jader et al 2001)
(Reed & Chandler 1958)
(Folstein et al 1987)
(Folstein et al 1987)
(Reed & Chandler 1958)
(Pearson et al 1955)
(Kokmen et al 1994)
(Kokmen et al 1994)
(Kurland 1958)
(Al-Jader et al 2001)
(Wright et al 1981)
(Wright et al 1981)
(Paradisi et al 2008)
(Avila-Giron 1973)
(Sepcić et al 1989)
(Scrimgeour & Pfumojena 1992)
S3

Warby et al. Supplemental
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S7

Warby et al. Supplemental
Supplementary Table 2: Definitions for the HTT haplogroups.
We are defining a 'haplogroup' as a cluster of similar haplotypes. Some of the SNP positions are variable (*) in the definitions. One tSNP used previously (tSNP#3, rs12506200, (Warby et al 2009) ) was incompatible with our current genotyping assay and was not included in the haplogroup definitions, but did not alter any haplogroup assignments. Haplogroup A is divided into several variants (A 1-5) as well as the 'A-Other' group, which is mostly singletons that do not cluster with other variants within haplogroup A. The 'Other' group are singletons which did not cluster into haplogroup A, B or C.
S8

Warby et al. Supplemental
Supplementary Table 3: Haplogroup frequency in each ethnic group.
The frequency and counts (in brackets) are indicated for each country, as well as the pooled results for
East Asia and Europe. The table is divided by HD chromosomes (top) and general population chromosomes based on CAG-tract size in the HTT gene. The number of chromosomes (# Chromo) and the average CAG-tract size for the group is presented (avg CAG). See Supplementary Table 2 for a description of the haplogroups and variants.
S9

Warby et al. Supplemental
East Asia
HD
>35CAG
Control
<27CAG OR p-value Sensitivity Specificity PPV NPV
C 24 29 5.2 0.000436 77.4% 60.3% 45.3% 86.3% non-C 7 44
Supplementary Table 4: Haplogroup C has increased risk for HD relative to non-C haplogroups in the East Asia. Odds ratio (OR), chisquare p-value, positive (PPV) and negative predictive value
(NPV) for East Asian chromosomes.
S10