Covariate adjusted correlation analysis with application to fmr1 premutation female carrier data

Damla Şentürk, Danh V. Nguyen, Flora Tassone, Randi J Hagerman, Raymond J. Carroll, Paul J Hagerman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Summary Motivated by molecular data on female premutation carriers of the fragile X mental retardation 1 (FMR1) gene, we present a new method of covariate adjusted correlation analysis to examine the association of messenger RNA (mRNA) and number of CGG repeat expansion in the FMR1 gene. The association between the molecular variables in female carriers needs to adjust for activation ratio (ActRatio), a measure which accounts for the protective effects of one normal X chromosome in females carriers. However, there are inherent uncertainties in the exact effects of ActRatio on the molecular measures of interest. To account for these uncertainties, we develop a flexible adjustment that accommodates both additive and multiplicative effects of ActRatio nonparametrically. The proposed adjusted correlation uses local conditional correlations, which are local method of moments estimators, to estimate the Pearson correlation between two variables adjusted for a third observable covariate. The local method of moments estimators are averaged to arrive at the final covariate adjusted correlation estimator, which is shown to be consistent. We also develop a test to check the nonparametric joint additive and multiplicative adjustment form. Simulation studies illustrate the efficacy of the proposed method. (Application to FMR1 premutation data on 165 female carriers indicates that the association between mRNA and CGG repeat after adjusting for ActRatio is stronger.) Finally, the results provide independent support for a specific jointly additive and multiplicative adjustment form for ActRatio previously proposed in the literature.

Original languageEnglish (US)
Pages (from-to)781-792
Number of pages12
JournalBiometrics
Volume65
Issue number3
DOIs
StatePublished - Sep 2009

Fingerprint

Correlation Analysis
Social Adjustment
Covariates
Activation
Chemical activation
Intellectual Disability
Multiplicative
Moment Estimator
Adjustment
Uncertainty
Method of Moments
Association reactions
messenger RNA
Method of moments
Messenger RNA
uncertainty
Genes
Gene
X Chromosome
Pearson Correlation

Keywords

  • Conditional correlation
  • Fragile X syndrome
  • Local method of moments
  • Mental retardation
  • Nonparametric partial correlation
  • Pearson correlation
  • Semiparametric modeling

ASJC Scopus subject areas

  • Applied Mathematics
  • Statistics and Probability
  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

Covariate adjusted correlation analysis with application to fmr1 premutation female carrier data. / Şentürk, Damla; Nguyen, Danh V.; Tassone, Flora; Hagerman, Randi J; Carroll, Raymond J.; Hagerman, Paul J.

In: Biometrics, Vol. 65, No. 3, 09.2009, p. 781-792.

Research output: Contribution to journalArticle

@article{f4bb8fc87e3547468e3b46a55f3b4611,
title = "Covariate adjusted correlation analysis with application to fmr1 premutation female carrier data",
abstract = "Summary Motivated by molecular data on female premutation carriers of the fragile X mental retardation 1 (FMR1) gene, we present a new method of covariate adjusted correlation analysis to examine the association of messenger RNA (mRNA) and number of CGG repeat expansion in the FMR1 gene. The association between the molecular variables in female carriers needs to adjust for activation ratio (ActRatio), a measure which accounts for the protective effects of one normal X chromosome in females carriers. However, there are inherent uncertainties in the exact effects of ActRatio on the molecular measures of interest. To account for these uncertainties, we develop a flexible adjustment that accommodates both additive and multiplicative effects of ActRatio nonparametrically. The proposed adjusted correlation uses local conditional correlations, which are local method of moments estimators, to estimate the Pearson correlation between two variables adjusted for a third observable covariate. The local method of moments estimators are averaged to arrive at the final covariate adjusted correlation estimator, which is shown to be consistent. We also develop a test to check the nonparametric joint additive and multiplicative adjustment form. Simulation studies illustrate the efficacy of the proposed method. (Application to FMR1 premutation data on 165 female carriers indicates that the association between mRNA and CGG repeat after adjusting for ActRatio is stronger.) Finally, the results provide independent support for a specific jointly additive and multiplicative adjustment form for ActRatio previously proposed in the literature.",
keywords = "Conditional correlation, Fragile X syndrome, Local method of moments, Mental retardation, Nonparametric partial correlation, Pearson correlation, Semiparametric modeling",
author = "Damla Şent{\"u}rk and Nguyen, {Danh V.} and Flora Tassone and Hagerman, {Randi J} and Carroll, {Raymond J.} and Hagerman, {Paul J}",
year = "2009",
month = "9",
doi = "10.1111/j.1541-0420.2008.01169.x",
language = "English (US)",
volume = "65",
pages = "781--792",
journal = "Biometrics",
issn = "0006-341X",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Covariate adjusted correlation analysis with application to fmr1 premutation female carrier data

AU - Şentürk, Damla

AU - Nguyen, Danh V.

AU - Tassone, Flora

AU - Hagerman, Randi J

AU - Carroll, Raymond J.

AU - Hagerman, Paul J

PY - 2009/9

Y1 - 2009/9

N2 - Summary Motivated by molecular data on female premutation carriers of the fragile X mental retardation 1 (FMR1) gene, we present a new method of covariate adjusted correlation analysis to examine the association of messenger RNA (mRNA) and number of CGG repeat expansion in the FMR1 gene. The association between the molecular variables in female carriers needs to adjust for activation ratio (ActRatio), a measure which accounts for the protective effects of one normal X chromosome in females carriers. However, there are inherent uncertainties in the exact effects of ActRatio on the molecular measures of interest. To account for these uncertainties, we develop a flexible adjustment that accommodates both additive and multiplicative effects of ActRatio nonparametrically. The proposed adjusted correlation uses local conditional correlations, which are local method of moments estimators, to estimate the Pearson correlation between two variables adjusted for a third observable covariate. The local method of moments estimators are averaged to arrive at the final covariate adjusted correlation estimator, which is shown to be consistent. We also develop a test to check the nonparametric joint additive and multiplicative adjustment form. Simulation studies illustrate the efficacy of the proposed method. (Application to FMR1 premutation data on 165 female carriers indicates that the association between mRNA and CGG repeat after adjusting for ActRatio is stronger.) Finally, the results provide independent support for a specific jointly additive and multiplicative adjustment form for ActRatio previously proposed in the literature.

AB - Summary Motivated by molecular data on female premutation carriers of the fragile X mental retardation 1 (FMR1) gene, we present a new method of covariate adjusted correlation analysis to examine the association of messenger RNA (mRNA) and number of CGG repeat expansion in the FMR1 gene. The association between the molecular variables in female carriers needs to adjust for activation ratio (ActRatio), a measure which accounts for the protective effects of one normal X chromosome in females carriers. However, there are inherent uncertainties in the exact effects of ActRatio on the molecular measures of interest. To account for these uncertainties, we develop a flexible adjustment that accommodates both additive and multiplicative effects of ActRatio nonparametrically. The proposed adjusted correlation uses local conditional correlations, which are local method of moments estimators, to estimate the Pearson correlation between two variables adjusted for a third observable covariate. The local method of moments estimators are averaged to arrive at the final covariate adjusted correlation estimator, which is shown to be consistent. We also develop a test to check the nonparametric joint additive and multiplicative adjustment form. Simulation studies illustrate the efficacy of the proposed method. (Application to FMR1 premutation data on 165 female carriers indicates that the association between mRNA and CGG repeat after adjusting for ActRatio is stronger.) Finally, the results provide independent support for a specific jointly additive and multiplicative adjustment form for ActRatio previously proposed in the literature.

KW - Conditional correlation

KW - Fragile X syndrome

KW - Local method of moments

KW - Mental retardation

KW - Nonparametric partial correlation

KW - Pearson correlation

KW - Semiparametric modeling

UR - http://www.scopus.com/inward/record.url?scp=67649095407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649095407&partnerID=8YFLogxK

U2 - 10.1111/j.1541-0420.2008.01169.x

DO - 10.1111/j.1541-0420.2008.01169.x

M3 - Article

C2 - 19173699

AN - SCOPUS:67649095407

VL - 65

SP - 781

EP - 792

JO - Biometrics

JF - Biometrics

SN - 0006-341X

IS - 3

ER -