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Tests and estimates of allelic association in complex inheritance

Tests and estimates of allelic association in complex inheritance
Tests and estimates of allelic association in complex inheritance
Family-based procedures such as the transmission disequilibrium test (TDT) were motivated by concern that sample-based methods to map disease genes by allelic association are not robust to population stratification, migration, and admixture. Other factors to consider in designing a study of allelic association are specification of gene action in a weakly parametric model, efficiency, diagnostic reliability for hypernormal individuals, interest in linkage and imprinting, and sibship composition. Family-based samples lend themselves to the TDT despite its inefficiency compared with cases and unrelated normal controls. The TDT has an efficiency of 1/2 for parent-offspring pairs and 2/3 for father-mother-child trios. Against cases and hypernormal controls, the efficiency is only 1/6 on the null hypothesis. Although dependent on marker gene frequency and other factors, efficiency for hypernormal controls is always greater than for random controls. Efficiency of the TDT is increased in multiplex families and by inclusion of normal sibs, approaching a case-control design with normal but not hypernormal controls. Isolated cases favor unrelated controls, and only in exceptional populations would avoidance of stratification justify a family-based design to map disease genes by allelic association.
transmission disequilibrium, test/case-control study
0027-8424
11389-11393
Morton, N.E.
c668e2be-074a-4a0a-a2ca-e8f51830ebb7
Collins, A.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Morton, N.E.
c668e2be-074a-4a0a-a2ca-e8f51830ebb7
Collins, A.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64

Morton, N.E. and Collins, A. (1998) Tests and estimates of allelic association in complex inheritance. Proceedings of the National Academy of Sciences, 95 (19), 11389-11393. (doi:10.1073/pnas.95.19.11389). (PMID:9736746)

Record type: Article

Abstract

Family-based procedures such as the transmission disequilibrium test (TDT) were motivated by concern that sample-based methods to map disease genes by allelic association are not robust to population stratification, migration, and admixture. Other factors to consider in designing a study of allelic association are specification of gene action in a weakly parametric model, efficiency, diagnostic reliability for hypernormal individuals, interest in linkage and imprinting, and sibship composition. Family-based samples lend themselves to the TDT despite its inefficiency compared with cases and unrelated normal controls. The TDT has an efficiency of 1/2 for parent-offspring pairs and 2/3 for father-mother-child trios. Against cases and hypernormal controls, the efficiency is only 1/6 on the null hypothesis. Although dependent on marker gene frequency and other factors, efficiency for hypernormal controls is always greater than for random controls. Efficiency of the TDT is increased in multiplex families and by inclusion of normal sibs, approaching a case-control design with normal but not hypernormal controls. Isolated cases favor unrelated controls, and only in exceptional populations would avoidance of stratification justify a family-based design to map disease genes by allelic association.

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More information

Published date: 15 September 1998
Keywords: transmission disequilibrium, test/case-control study
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 362513
URI: https://eprints.soton.ac.uk/id/eprint/362513
ISSN: 0027-8424
PURE UUID: 2c34b148-15a8-4245-ac92-97c074ba8321
ORCID for A. Collins: ORCID iD orcid.org/0000-0001-7108-0771

Catalogue record

Date deposited: 26 Feb 2014 12:36
Last modified: 06 Jun 2018 13:11

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