A comparison of case-control and family-based association methods: the example of sickle-cell and malaria.
There has been much debate about the relative merits of population- and family-based strategies for testing genetic association, yet there is little empirical data that directly compare the two approaches. Here we compare case-control and transmission/disequilibrium test (TDT) study designs using a...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2005
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| _version_ | 1797096596186333184 |
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| author | Ackerman, H Usen, S Jallow, M Sisay-Joof, F Pinder, M Kwiatkowski, D |
| author_facet | Ackerman, H Usen, S Jallow, M Sisay-Joof, F Pinder, M Kwiatkowski, D |
| author_sort | Ackerman, H |
| collection | OXFORD |
| description | There has been much debate about the relative merits of population- and family-based strategies for testing genetic association, yet there is little empirical data that directly compare the two approaches. Here we compare case-control and transmission/disequilibrium test (TDT) study designs using a well-established genetic association, the protective effect of the sickle-cell trait against severe malaria. We find that the two methods give similar estimates of the level of protection (case-control odds ratio = 0.10, 95% confidence interval 0.03-0.23; family-based estimate of the odds ratio = 0.11, 95% confidence interval 0.04-0.25) and similar statistical significance of the result (case-control: chi2= 41.26, p= 10(-10), TDT: chi2= 39.06, p= 10(-10)) when 315 TDT cases are compared to 583 controls. We propose a family plus population control study design, which allows both case-control and TDT analysis of the cases. This combination is robust against the respective weaknesses of the case-control and TDT study designs, namely population structure and segregation distortion. The combined study design is especially cost-effective when cases are difficult to ascertain and, when the case-control and TDT results agree, offers greater confidence in the result. |
| first_indexed | 2024-03-07T04:44:06Z |
| format | Journal article |
| id | oxford-uuid:d2a58550-e638-4e3a-8c69-0103c2d4f82a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:44:06Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:d2a58550-e638-4e3a-8c69-0103c2d4f82a2022-03-27T08:05:33ZA comparison of case-control and family-based association methods: the example of sickle-cell and malaria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d2a58550-e638-4e3a-8c69-0103c2d4f82aEnglishSymplectic Elements at Oxford2005Ackerman, HUsen, SJallow, MSisay-Joof, FPinder, MKwiatkowski, DThere has been much debate about the relative merits of population- and family-based strategies for testing genetic association, yet there is little empirical data that directly compare the two approaches. Here we compare case-control and transmission/disequilibrium test (TDT) study designs using a well-established genetic association, the protective effect of the sickle-cell trait against severe malaria. We find that the two methods give similar estimates of the level of protection (case-control odds ratio = 0.10, 95% confidence interval 0.03-0.23; family-based estimate of the odds ratio = 0.11, 95% confidence interval 0.04-0.25) and similar statistical significance of the result (case-control: chi2= 41.26, p= 10(-10), TDT: chi2= 39.06, p= 10(-10)) when 315 TDT cases are compared to 583 controls. We propose a family plus population control study design, which allows both case-control and TDT analysis of the cases. This combination is robust against the respective weaknesses of the case-control and TDT study designs, namely population structure and segregation distortion. The combined study design is especially cost-effective when cases are difficult to ascertain and, when the case-control and TDT results agree, offers greater confidence in the result. |
| spellingShingle | Ackerman, H Usen, S Jallow, M Sisay-Joof, F Pinder, M Kwiatkowski, D A comparison of case-control and family-based association methods: the example of sickle-cell and malaria. |
| title | A comparison of case-control and family-based association methods: the example of sickle-cell and malaria. |
| title_full | A comparison of case-control and family-based association methods: the example of sickle-cell and malaria. |
| title_fullStr | A comparison of case-control and family-based association methods: the example of sickle-cell and malaria. |
| title_full_unstemmed | A comparison of case-control and family-based association methods: the example of sickle-cell and malaria. |
| title_short | A comparison of case-control and family-based association methods: the example of sickle-cell and malaria. |
| title_sort | comparison of case control and family based association methods the example of sickle cell and malaria |
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