Nature Genetics
- 38, 556 - 560 (2006)
Published online: 2 April 2006; | doi:10.1038/ng1770
Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studiesSusan Service1, Joseph DeYoung2, Maria Karayiorgou3, J Louw Roos4, Herman Pretorious4, Gabriel Bedoya5, Jorge Ospina6, Andres Ruiz-Linares5, 7, António Macedo8, Joana Almeida Palha9, Peter Heutink10, 11, Yurii Aulchenko12, Ben Oostra12, Cornelia van Duijn12, Marjo-Riitta Jarvelin13, 14, Teppo Varilo15, 16, Lynette Peddle17, Proton Rahman18, Giovanna Piras19, Maria Monne19, Sarah Murray20, Luana Galver20, Leena Peltonen15, 16, Chiara Sabatti21, 22, Andrew Collins23 & Nelson Freimer1, 24, 251
Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA. 2
Southern California Genotyping Consortium, University of California, Los Angeles, California 90095, USA. 3
Rockefeller University, New York, New York 10021, USA. 4
University of Pretoria, Department of Psychiatry & Weskoppies Hospital, Pretoria, Republic of South Africa 0001. 5
Laboratory of Molecular Genetics, University of Antioquia, Medellin, Colombia. 6
Department of Psychiatry, University of Antioquia, Medellin, Colombia. 7
The Galton Laboratory, Department of Biology (Wolfson House), University College London, London NW1 2HE, UK. 8
Institute of Medical Psychology, Faculty of Medicine, University of Coimbra, 3000-033 Coimbra, Portugal. 9
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4704-553 Braga, Portugal. 10
Department of Human Genetics, Section of Medical Genomics, Vrije University and Vrije University Medical Center, 1081 BT, Amsterdam, The Netherlands. 11
Center for Neurogenomics and Cognitive Research, Vrije University and Vrije University Medical Center, 1081 BT, Amsterdam, The Netherlands. 12
Genetic Epidemiology Unit, Departments of Epidemiology & Biostatistics and Clinical Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands. 13
Department of Public Health Science and General Practice, University of Oulu, 90220 Oulu, Finland. 14
Department of Epidemiology and Public Health, Imperial College London, London W2 1PG, UK. 15
Department of Medical Genetics, University of Helsinki, 00290 Helsinki, Finland. 16
Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, 00290 Helsinki, Finland. 17
Newfound Genomics, 187 Lemarchant Road, St. John's, Newfoundland, Canada A1C 2H5. 18
Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1C 5S7. 19
Division of Haematology, 'San Francesco' Hospital, ASL3 Nuoro, Italy. 20
Illumina, Inc., 9885 Towne Centre Dr., San Diego, California 92121, USA. 21
Department of Human Genetics, University of California, Los Angeles, California 90095 USA. 22
Department of Statistics, University of California, Los Angeles, California 90095 USA. 23
Human Genetics Research Division, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YA, UK. 24
The Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California 90095 USA. 25
Department of Psychiatry, University of California, Los Angeles, California 90095 USA.
Correspondence should be addressed to Nelson Freimer nfreimer@mednet.ucla.edu The genome-wide distribution of linkage disequilibrium (LD) determines the strategy for selecting markers for association studies, but it varies between populations. We assayed LD in large samples (200 individuals) from each of 11 well-described population isolates and an outbred European-derived sample, using SNP markers spaced across chromosome 22. Most isolates show substantially higher levels of LD than the outbred sample and many fewer regions of very low LD (termed 'holes'). Young isolates known to have had relatively few founders show particularly extensive LD with very few holes; these populations offer substantial advantages for genome-wide association mapping.
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