Incorporating endophenotypes into allele‐sharing based linkage tests

Wang, Wen Chang; Chang, I‐Shou; Chang, Chin-Hao; Curb, David; Ho, ­Low‐Tone; Hsiung, Chao A.

doi:10.1002/gepi.20133

Cited by 3 publications

(3 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To our knowledge, no study has been conducted to determine the implication of the T323C polymorphism of ET A receptor gene in IR, an intermediate metabolic phenotype for hypertension (43). Thus, we further explored the association of the ET A receptor’s T323C polymorphism with the MetS related quantitative traits.…”

Section: Discussionmentioning

confidence: 99%

Endothelin Type A Receptor Genotype is a Determinant of Quantitative Traits of Metabolic Syndrome in Asian Hypertensive Families: A SAPPHIRe Study

Hsu

Hsiao

et al. 2013

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

Co-heritability of hypertension and insulin resistance (IR) within families not only implies genetic susceptibility may be responsible for these complex traits but also suggests a rational that biological candidate genes for hypertension may serve as markers for features of the metabolic syndrome (MetS). Thus we determined whether the T323C polymorphism (rs5333) of endothelin type A (ETA) receptor, a predominant receptor evoking potent vasoconstrictive action of endothelin-1, contributes to susceptibility to IR-associated hypertension in 1694 subjects of Chinese and Japanese origins. Blood pressures (BPs) and biochemistries were measured. Fasting insulin level, insulin-resistance homeostasis model assessment (HOMAIR) score, and area under curve of insulin concentration (AUCINS) were selected for assessing insulin sensitivity. Genotypes were obtained by methods of polymerase chain reaction-restriction fragment length polymorphism. Foremost findings were that minor allele frequency of the T323C polymorphism was noticeable lower in our overall Asian subjects compared to multi-national population reported in gene database; moreover both the genotypic and allelic frequencies of the polymorphism were significantly different between the two ethnic groups we studied. The genotype distributions at TT/TC/CC were 65, 31, 4% in Chinese and 51, 41, 8% in Japanese, respectively (p < 0.0001). Additionally, carriers of the C homozygote revealed characteristics of IR, namely significantly higher levels of fasting insulin, HOMAIR score, and AUCINS at 29.3, 35.3, and 39.3%, respectively, when compared to their counterparts with TT/TC genotypes in Chinese. Meanwhile, the CC genotype was associated with a higher level of high density lipoprotein cholesterol in Japanese. No association of the polymorphism with BP was observed. This study demonstrated for the first time that T323C polymorphism of ETA receptor gene was associated with an adverse insulin response in Chinese and a favorite atherogenic index in Japanese.

show abstract

Section: Discussionmentioning

confidence: 99%

Endothelin Type A Receptor Genotype is a Determinant of Quantitative Traits of Metabolic Syndrome in Asian Hypertensive Families: A SAPPHIRe Study

Hsu

Hsiao

et al. 2013

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is the latter that we will adhere to in the present report, which typically lay relatively proximal along the genotype-phenotype continuum [Gottesman and Gould, 2003;Almasy and Blangero, 2001]. Such informative latent components provide simpler clues to the genetic underpinnings of clinical phenotypes of the disease, as demonstrated by their recent use in both linkage and association analysis [Pan et al, 2006;Wang et al, 2006]. In studies of complex diseases, various endophenotypes may be extracted from data on physiological challenges, biochemical assays, and physiological measures.…”

Section: Introductionmentioning

confidence: 91%

Enhanced detection of genetic association of hypertensive heart disease by analysis of latent phenotypes

Flores

Fuentes

et al. 2008

Genetic Epidemiology

View full text Add to dashboard Cite

Hypertension and hypertensive heart disease (HHD) are inter-related phenotypes frequently observed with other comorbidities such as diabetes, obesity, and dyslipidemia, which probably reflect the complex gene-gene and/or gene-environment interactions resulting in HHD. The complexity of HHD led us to examine intermediate phenotypes (e.g., echocardiographically-derived measures) for simpler clues to the genetic underpinnings of the disease. We applied the method of independent component analysis to a prospective study of the metabolic predictors of left ventricular hypertrophy and extracted latent traits of HHD from panels of multi-dimensional anthropomorphic, hemodynamic echocardiographic and metabolic data. Based on the latent trait values, classification of subjects into different risk groups for HHD captured meaningful subtypes of the disease as reflected in the distributions of primary clinical indicators. Furthermore, we detected genetic associations of the latent HHD traits with single nucleotide polymorphisms in three candidate genes in the peroxisome proliferator-activated receptors complex, for which no significant association was found with the original clinical indicators of HHD. Consensus analysis of the results from repeated independent component analysis runs showed satisfactory robustness and estimated about 3-4 separate unseen sources for the observed HHD-related outcomes.

show abstract

“…Incorporating EDPs into linkage analyses of complex diseases has been useful in improving power to detect linked loci that were either not detected at all, or that showed much weaker linkage when the clinical disorder was considered alone (Arolt et al, 1999; Freedman et al, 1997; Gasperoni et al, 2003; Ghosh et al, 2003; Greenberg et al, 2000; Hallmayer et al, 2005; Jones et al, 2004; Keating et al, 1991; Keating and Sanguinetti, 2001; Marlow et al, 2003; Matthysse et al, 2004; Spence et al, 2006; Wang et al, 2006; Wilcox et al, 2002). Most of the cited studies considered quantitative EDPs.…”

Section: Introductionmentioning

confidence: 99%

The power of linkage analysis of a disease-related endophenotype using asymmetrically ascertained sib pairs

Sung

Levy

et al. 2009

Computational Statistics & Data Analysis

View full text Add to dashboard Cite

A linkage study of a qualitative disease endophenotype in a sample of sib pairs, consisting of one disease affected proband and one sibling is considered. The linkage statistic compares marker allele sharing with the proband in siblings with an abnormal endophenotype to siblings with the normal endophenotype. Expressions for the distribution of this linkage statistic, in terms of the recombination fraction are derived and (1) the genetic parameter values (allele frequency and endophenotype and disease penetrance) and (2) the abnormal endophenotype rates in the population and in classes of relatives of disease affected probands. It is then shown that when either the disease or the abnormal endophenotype has additive penetrance, the expressions simplify to a monotonic function of the difference between abnormal endophenotype rates in siblings and in the population. Thought disorder is considered as a putative schizophrenia endophenotype. Forty sets of genetic parameter values that correspond to the known prevalence values for thought disorder in schizophrenic patients, siblings of schizophrenics and the general population are evaluated. For these genetic parameter values, numerical results show that the test statistic has>70% power (α = 0.0001) in general with a sample of 200 or more proband-sibling pairs to detect the linkage between a marker (θ = 0.01), and a locus pleiotropic for schizophrenia and thought disorder.

show abstract

Incorporating endophenotypes into allele‐sharing based linkage tests

Cited by 3 publications

References 22 publications

Endothelin Type A Receptor Genotype is a Determinant of Quantitative Traits of Metabolic Syndrome in Asian Hypertensive Families: A SAPPHIRe Study

Endothelin Type A Receptor Genotype is a Determinant of Quantitative Traits of Metabolic Syndrome in Asian Hypertensive Families: A SAPPHIRe Study

Enhanced detection of genetic association of hypertensive heart disease by analysis of latent phenotypes

The power of linkage analysis of a disease-related endophenotype using asymmetrically ascertained sib pairs

Contact Info

Product

Resources

About