Genome scanning by composite likelihood
Genome scanning by composite likelihood
Ambitious programs have recently been advocated or launched to create genomewide databases for meta-analysis ofassociation between DNA markers and phenotypes of medical and/or social concern. A necessary but not sufficientcondition for success in association mapping is that the data give accurate estimates of both genomic location and its standard error, which are provided for multifactorial phenotypes by composite likelihood. That class includes the Malecot model, which we here apply with an illustrative example. This preliminary analysis leads to five inferences: permutation of cases and controls provides a test of association free of autocorrelation; two hypotheses give similar estimates, but one is consistently more accurate; estimation of the false-discovery rate is extended to causal genes in a small proportion of regions; the minimal data for successful meta-analysis are inferred; and power is robust for all genomic factors except minor-allele frequency. An extension to meta-analysis is proposed. Other approaches to genome scanning and meta analysis should, if possible, be similarly extended so that their operating characteristics can be compared.
MORTON, N
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MANIATIS, N
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ZHANG, WH
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ENNIS, S
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COLLINS, A
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1 January 2007
MORTON, N
c668e2be-074a-4a0a-a2ca-e8f51830ebb7
MANIATIS, N
44b156c9-ca84-43c3-a91b-42d2d500c039
ZHANG, WH
639e1bd7-72bd-4dfa-a56a-ea24a68c0a12
ENNIS, S
7b57f188-9d91-4beb-b217-09856146f1e9
COLLINS, A
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
MORTON, N, MANIATIS, N, ZHANG, WH, ENNIS, S and COLLINS, A
(2007)
Genome scanning by composite likelihood.
American Journal of Human Genetics, 80 (1).
(doi:10.1086/510401).
Abstract
Ambitious programs have recently been advocated or launched to create genomewide databases for meta-analysis ofassociation between DNA markers and phenotypes of medical and/or social concern. A necessary but not sufficientcondition for success in association mapping is that the data give accurate estimates of both genomic location and its standard error, which are provided for multifactorial phenotypes by composite likelihood. That class includes the Malecot model, which we here apply with an illustrative example. This preliminary analysis leads to five inferences: permutation of cases and controls provides a test of association free of autocorrelation; two hypotheses give similar estimates, but one is consistently more accurate; estimation of the false-discovery rate is extended to causal genes in a small proportion of regions; the minimal data for successful meta-analysis are inferred; and power is robust for all genomic factors except minor-allele frequency. An extension to meta-analysis is proposed. Other approaches to genome scanning and meta analysis should, if possible, be similarly extended so that their operating characteristics can be compared.
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Published date: 1 January 2007
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Local EPrints ID: 470714
URI: http://eprints.soton.ac.uk/id/eprint/470714
ISSN: 0002-9297
PURE UUID: 2105d6c4-d2d5-454e-860a-9320cc08b2cb
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Date deposited: 18 Oct 2022 16:49
Last modified: 17 Mar 2024 02:49
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Author:
N MORTON
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N MANIATIS
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WH ZHANG
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