Disentangling fetal and maternal susceptibility for pre-eclampsia: A British multicenter candidate-gene study

Linda Morgan; M. Farrall; P. N. Baker; F. Broughton Pipkin; N. Kalsheker; S. O’Malley; M. Henfrey; S. Arulkumaran; I. Symonds; A. Cameron; A. Dominiczak; M. McDade; W. Kwong Lee; J. McCulloch; M. Caulfield; M. Habiba; C. Dodd; M. Kilby; L. Davies; S. Macphail; P. M.S. O’Brien; K. O’Shaughnessy; B. Newcombe; P. De La Salle; C. Redman; P. Jarrett; M. De Swiet; C. Williamson; E. Byford; F. Cheng; J. J. Walker; L. Samwiil; G. Chapman; E. Dennehy; R. Keys; S. Bjornsson; C. Mercer; M. Mohajer; G. Thompson; M. N. Fitzgibbon; G. Hackett; K. Hinshaw; B. Lim; D. T.Y. Liu; W. Mackenzie; M. Selinger; I. Scudamore; C. Sparey; D. Tuffnell; S. Ward; The GOPEC Consortium

doi:10.1086/431245

Disentangling fetal and maternal susceptibility for pre-eclampsia: A British multicenter candidate-gene study

Linda Morgan^*, M. Farrall, P. N. Baker, F. Broughton Pipkin, N. Kalsheker, S. O’Malley, M. Henfrey, S. Arulkumaran, I. Symonds, A. Cameron, A. Dominiczak, M. McDade, W. Kwong Lee, J. McCulloch, M. Caulfield, M. Habiba, C. Dodd, M. Kilby, L. Davies, S. MacphailP. M.S. O’Brien, K. O’Shaughnessy, B. Newcombe, P. De La Salle, C. Redman, P. Jarrett, M. De Swiet, C. Williamson, E. Byford, F. Cheng, J. J. Walker, L. Samwiil, G. Chapman, E. Dennehy, R. Keys, S. Bjornsson, C. Mercer, M. Mohajer, G. Thompson, M. N. Fitzgibbon, G. Hackett, K. Hinshaw, B. Lim, D. T.Y. Liu, W. Mackenzie, M. Selinger, I. Scudamore, C. Sparey, D. Tuffnell, S. Ward, The GOPEC Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

92 Citations (Scopus)

Abstract

The Genetics of Pre-Eclampsia (GOPEC) collaboration aims to identify genetic factors in U.K. families affected by pre-eclampsia. A number of genetic studies have reported associations with pre-eclampsia, but attempts to replicate these findings have yielded inconsistent results. We describe the results of extensive genotyping of seven candidate genes previously reported as conferring susceptibility to pre-eclampsia. Six hundred fifty-seven women affected by pre-eclampsia and their families were genotyped at 28 single-nucleotide polymorphisms in the genes encoding angiotensinogen, the angiotensin receptors, factor V Leiden variant, methylene tetrahydrofolate reductase, nitric oxide synthase, and TNFα. Genotypes were analyzed by the transmission/disequilibrium test. Genotype risk ratios (GRRs) associated with maternal genotypes had a range of 0.70−1.16; GRRs associated with fetal genotypes had a range of 0.72−1.11. No GRR achieved the prespecified criteria for statistical significance (posterior probability >.05). We conclude that none of the genetic variants tested in this large study of strictly defined pre-eclamptic pregnancies confers a high risk of disease. The results emphasize the importance of conducting rigorously designed studies of adequate size to provide precise genetic risks with narrow confidence intervals, if overreporting of falsepositive results is to be avoided.

Original language	English
Pages (from-to)	127-131
Number of pages	5
Journal	American Journal of Human Genetics
Volume	77
Issue number	1
Early online date	11 May 2005
DOIs	https://doi.org/10.1086/431245
Publication status	Published - Jul 2005
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2005 by The American Society of Human Genetics.

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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Morgan, L., Farrall, M., Baker, P. N., Pipkin, F. B., Kalsheker, N., O’Malley, S., Henfrey, M., Arulkumaran, S., Symonds, I., Cameron, A., Dominiczak, A., McDade, M., Lee, W. K., McCulloch, J., Caulfield, M., Habiba, M., Dodd, C., Kilby, M., Davies, L., ... The GOPEC Consortium (2005). Disentangling fetal and maternal susceptibility for pre-eclampsia: A British multicenter candidate-gene study. American Journal of Human Genetics, 77(1), 127-131. https://doi.org/10.1086/431245

@article{99136686eb524b71b5628fda8d1384df,

title = "Disentangling fetal and maternal susceptibility for pre-eclampsia: A British multicenter candidate-gene study",

abstract = "The Genetics of Pre-Eclampsia (GOPEC) collaboration aims to identify genetic factors in U.K. families affected by pre-eclampsia. A number of genetic studies have reported associations with pre-eclampsia, but attempts to replicate these findings have yielded inconsistent results. We describe the results of extensive genotyping of seven candidate genes previously reported as conferring susceptibility to pre-eclampsia. Six hundred fifty-seven women affected by pre-eclampsia and their families were genotyped at 28 single-nucleotide polymorphisms in the genes encoding angiotensinogen, the angiotensin receptors, factor V Leiden variant, methylene tetrahydrofolate reductase, nitric oxide synthase, and TNFα. Genotypes were analyzed by the transmission/disequilibrium test. Genotype risk ratios (GRRs) associated with maternal genotypes had a range of 0.70−1.16; GRRs associated with fetal genotypes had a range of 0.72−1.11. No GRR achieved the prespecified criteria for statistical significance (posterior probability >.05). We conclude that none of the genetic variants tested in this large study of strictly defined pre-eclamptic pregnancies confers a high risk of disease. The results emphasize the importance of conducting rigorously designed studies of adequate size to provide precise genetic risks with narrow confidence intervals, if overreporting of falsepositive results is to be avoided.",

author = "Linda Morgan and M. Farrall and Baker, {P. N.} and Pipkin, {F. Broughton} and N. Kalsheker and S. O{\textquoteright}Malley and M. Henfrey and S. Arulkumaran and I. Symonds and A. Cameron and A. Dominiczak and M. McDade and Lee, {W. Kwong} and J. McCulloch and M. Caulfield and M. Habiba and C. Dodd and M. Kilby and L. Davies and S. Macphail and O{\textquoteright}Brien, {P. M.S.} and K. O{\textquoteright}Shaughnessy and B. Newcombe and {De La Salle}, P. and C. Redman and P. Jarrett and {De Swiet}, M. and C. Williamson and E. Byford and F. Cheng and Walker, {J. J.} and L. Samwiil and G. Chapman and E. Dennehy and R. Keys and S. Bjornsson and C. Mercer and M. Mohajer and G. Thompson and Fitzgibbon, {M. N.} and G. Hackett and K. Hinshaw and B. Lim and Liu, {D. T.Y.} and W. Mackenzie and M. Selinger and I. Scudamore and C. Sparey and D. Tuffnell and S. Ward and {The GOPEC Consortium}",

note = "Publisher Copyright: {\textcopyright} 2005 by The American Society of Human Genetics.",

year = "2005",

month = jul,

doi = "10.1086/431245",

language = "English",

volume = "77",

pages = "127--131",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "1",

}

Morgan, L, Farrall, M, Baker, PN, Pipkin, FB, Kalsheker, N, O’Malley, S, Henfrey, M, Arulkumaran, S, Symonds, I, Cameron, A, Dominiczak, A, McDade, M, Lee, WK, McCulloch, J, Caulfield, M, Habiba, M, Dodd, C, Kilby, M, Davies, L, Macphail, S, O’Brien, PMS, O’Shaughnessy, K, Newcombe, B, De La Salle, P, Redman, C, Jarrett, P, De Swiet, M, Williamson, C, Byford, E, Cheng, F, Walker, JJ, Samwiil, L, Chapman, G, Dennehy, E, Keys, R, Bjornsson, S, Mercer, C, Mohajer, M, Thompson, G, Fitzgibbon, MN, Hackett, G, Hinshaw, K, Lim, B, Liu, DTY, Mackenzie, W, Selinger, M, Scudamore, I, Sparey, C, Tuffnell, D, Ward, S & The GOPEC Consortium 2005, 'Disentangling fetal and maternal susceptibility for pre-eclampsia: A British multicenter candidate-gene study', American Journal of Human Genetics, vol. 77, no. 1, pp. 127-131. https://doi.org/10.1086/431245

TY - JOUR

T1 - Disentangling fetal and maternal susceptibility for pre-eclampsia: A British multicenter candidate-gene study

AU - Morgan, Linda

AU - Farrall, M.

AU - Baker, P. N.

AU - Pipkin, F. Broughton

AU - Kalsheker, N.

AU - O’Malley, S.

AU - Henfrey, M.

AU - Arulkumaran, S.

AU - Symonds, I.

AU - Cameron, A.

AU - Dominiczak, A.

AU - McDade, M.

AU - Lee, W. Kwong

AU - McCulloch, J.

AU - Caulfield, M.

AU - Habiba, M.

AU - Dodd, C.

AU - Kilby, M.

AU - Davies, L.

AU - Macphail, S.

AU - O’Brien, P. M.S.

AU - O’Shaughnessy, K.

AU - Newcombe, B.

AU - De La Salle, P.

AU - Redman, C.

AU - Jarrett, P.

AU - De Swiet, M.

AU - Williamson, C.

AU - Byford, E.

AU - Cheng, F.

AU - Walker, J. J.

AU - Samwiil, L.

AU - Chapman, G.

AU - Dennehy, E.

AU - Keys, R.

AU - Bjornsson, S.

AU - Mercer, C.

AU - Mohajer, M.

AU - Thompson, G.

AU - Fitzgibbon, M. N.

AU - Hackett, G.

AU - Hinshaw, K.

AU - Lim, B.

AU - Liu, D. T.Y.

AU - Mackenzie, W.

AU - Selinger, M.

AU - Scudamore, I.

AU - Sparey, C.

AU - Tuffnell, D.

AU - Ward, S.

AU - The GOPEC Consortium

PY - 2005/7

Y1 - 2005/7

N2 - The Genetics of Pre-Eclampsia (GOPEC) collaboration aims to identify genetic factors in U.K. families affected by pre-eclampsia. A number of genetic studies have reported associations with pre-eclampsia, but attempts to replicate these findings have yielded inconsistent results. We describe the results of extensive genotyping of seven candidate genes previously reported as conferring susceptibility to pre-eclampsia. Six hundred fifty-seven women affected by pre-eclampsia and their families were genotyped at 28 single-nucleotide polymorphisms in the genes encoding angiotensinogen, the angiotensin receptors, factor V Leiden variant, methylene tetrahydrofolate reductase, nitric oxide synthase, and TNFα. Genotypes were analyzed by the transmission/disequilibrium test. Genotype risk ratios (GRRs) associated with maternal genotypes had a range of 0.70−1.16; GRRs associated with fetal genotypes had a range of 0.72−1.11. No GRR achieved the prespecified criteria for statistical significance (posterior probability >.05). We conclude that none of the genetic variants tested in this large study of strictly defined pre-eclamptic pregnancies confers a high risk of disease. The results emphasize the importance of conducting rigorously designed studies of adequate size to provide precise genetic risks with narrow confidence intervals, if overreporting of falsepositive results is to be avoided.

AB - The Genetics of Pre-Eclampsia (GOPEC) collaboration aims to identify genetic factors in U.K. families affected by pre-eclampsia. A number of genetic studies have reported associations with pre-eclampsia, but attempts to replicate these findings have yielded inconsistent results. We describe the results of extensive genotyping of seven candidate genes previously reported as conferring susceptibility to pre-eclampsia. Six hundred fifty-seven women affected by pre-eclampsia and their families were genotyped at 28 single-nucleotide polymorphisms in the genes encoding angiotensinogen, the angiotensin receptors, factor V Leiden variant, methylene tetrahydrofolate reductase, nitric oxide synthase, and TNFα. Genotypes were analyzed by the transmission/disequilibrium test. Genotype risk ratios (GRRs) associated with maternal genotypes had a range of 0.70−1.16; GRRs associated with fetal genotypes had a range of 0.72−1.11. No GRR achieved the prespecified criteria for statistical significance (posterior probability >.05). We conclude that none of the genetic variants tested in this large study of strictly defined pre-eclamptic pregnancies confers a high risk of disease. The results emphasize the importance of conducting rigorously designed studies of adequate size to provide precise genetic risks with narrow confidence intervals, if overreporting of falsepositive results is to be avoided.

U2 - 10.1086/431245

DO - 10.1086/431245

M3 - Article

C2 - 15889386

AN - SCOPUS:20544448502

SN - 0002-9297

VL - 77

SP - 127

EP - 131

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 1

ER -

Disentangling fetal and maternal susceptibility for pre-eclampsia: A British multicenter candidate-gene study

Abstract

Bibliographical note

ASJC Scopus subject areas

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