A family-based robust multivariate association test using maximum statistic.


:For characterizing the genetic mechanisms of complex diseases familial data with multiple correlated quantitative traits are usually collected in genetic studies. To analyze such data, various multivariate tests have been proposed to investigate the association between the underlying disease genes and the multiple traits. Although these multivariate association tests may have better power performance than the univariate association tests, they suffer from loss of testing power when the genetic models of the putative genes are misspecified. To address the problem, in this paper we aim to develop a family-based robust multivariate association test. We will first establish the optimal multivariate score tests for the recessive, additive, and dominant genetic models. Based on these optimal tests, a maximum-type robust multivariate association test is then obtained. Simulations are conducted to compare the power of our method with that of other existing multivariate methods. The results show that the robust multivariate test does manifest the robustness in power over all plausible genetic models. A practical data set is applied to demonstrate the applicability of our approach. The results suggest that the robust multivariate test is more powerful than the robust univariate test when dealing with multiple quantitative traits.


Ann Hum Genet


Annals of human genetics


Hsieh TJ,Chang SH,Tai JJ




Has Abstract


2014-03-01 00:00:00












  • New variants of Ps salivary polymorphic proteins.

    abstract::Electrophoretic analysis of the Ps protein demonstrated the existence of phenotypes additional to those described by Azen & Denniston (1980). A hypothesis that the polymorphism of the Ps protein is determined by five expressed and one unexpressed alleles was supported by family studies. The gene frequencies in a Japan...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Minaguchi K,Shirotani T,Suzuki K

    更新日期:1988-01-01 00:00:00

  • Simultaneous selection of the wild-type genotypes of the G894T and 4B/ 4A polymorphisms of NOS3 associate with high-altitude adaptation.

    abstract::The routine performance of high-altitude (HA) natives in the hypoxic environment of HA exemplifies the process of adaptation mainly through natural selection. The recent therapeutic application of nitric oxide (NO) in HA disorders, for the improvement of oxygenation and vasodilation, ushered us to investigate the endo...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Ahsan A,Norboo T,Baig MA,Qadar Pasha MA

    更新日期:2005-05-01 00:00:00

  • Localization of the oncogene c-erbA1 immediately proximal to the acute promyelocytic leukaemia breakpoint on chromosome 17.

    abstract::Using in situ hybridization, c-erbA1 has been mapped immediately distal to the translocation breakpoint on chromosome 17 in fibroblasts with a karyotype 46,XX, t(15;17)(q22;q11). Previous work has shown that c-erbA1 is proximal to the translocation breakpoint on chromosome 17 in the t(15;17)(q22;q12-21) in acute promy...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Sheer D,Sheppard DM,le Beau M,Rowley JD,San Roman C,Solomon E

    更新日期:1985-07-01 00:00:00

  • Correlated odour threshold bimodality of two out of three synthetic musks.

    abstract::The odour threshold bimodality for exaltolide described by Whissell-Buechy & Amoore (1973) among American whites is confirmed for a population sample in London. A highly correlated bimodality presumed to be caused by the absence of inactivity of certain receptor sites is shown to exist for another structurally differe...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Kalmus H,Seedburgh D

    更新日期:1975-05-01 00:00:00

  • An extension of the regression of offspring on mid-parent to test for association and estimate locus-specific heritability: the revised ROMP method.

    abstract::The Regression of Offspring on Mid-Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMP...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Roy-Gagnon MH,Mathias RA,Fallin MD,Jee SH,Broman KW,Wilson AF

    更新日期:2008-01-01 00:00:00

  • Tests of association between quantitative traits and haplotypes in a reduced-dimensional space.

    abstract::Candidate gene association tests are currently performed using several intragenic SNPs simultaneously, by testing SNP haplotype or genotype effects in multifactorial diseases or traits. The number of haplotypes drastically increases with an increase in the number of typed SNPs. As a result, large numbers of haplotypes...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Sha Q,Dong J,Jiang R,Zhang S

    更新日期:2005-11-01 00:00:00

  • Molecular scanning for mutations in the melanocortin-4 receptor gene in obese/diabetic Japanese.

    abstract::Decreased function of the melanocortin-4 receptor (MC4R) was reported to cause late-onset obesity and insulin resistance in rodents. Thus mutations in the MC4R gene drew strong attention as a possible cause of obesity and diabetes. We screened for mutations in the MC4R gene in extremely obese [body mass index (BMI) > ...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Ohshiro Y,Sanke T,Ueda K,Shimajiri Y,Nakagawa T,Tsunoda K,Nishi M,Sasaki H,Takasu N,Nanjo K

    更新日期:1999-11-01 00:00:00

  • N-ras-like sequences on chromosomes 9, 6 and 22 with a polymorphism at the chromosome 9 locus.

    abstract::Two clones, pCN1 and pCN2, which together form full-length cDNA for N-ras, were used to search for restriction fragment length polymorphisms. pCN2, which entirely consists of 3' non-translated sequences, revealed more bands on DNA transfer hybridizations than could be accounted for using the known restriction map of N...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Middleton-Price H,Spurr N,Hall A,Malcolm S

    更新日期:1988-07-01 00:00:00

  • Very close linkage between D2S1 and ACP1 on chromosome 2p.

    abstract::The genomic DNA-probe L2.30 was used to assign D2S1 to 2p23-pter by in situ hybridization. The RFLP revealed by BglII was then used for linkage studies in the Oslo-NHIK families segregating for the acid phosphatase ACP1 protein polymorphism. Evidence for very close linkage was found by a lod score of +17.17 at recombi...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Lothe RA,Gedde-Dahl T,Olaisen B,Bakker E,Pearson P

    更新日期:1986-10-01 00:00:00

  • Search for the PARK3 founder haplotype in a large cohort of patients with Parkinson's disease from northern Germany.

    abstract::A founder haplotype on chromosome 2p for autosomal dominant Parkinson's disease (PD) has been postulated for two families of Northern European descent, and a new mutation in the alpha-synuclein gene (Ala30Pro) has been found in a German PD family. We evaluated 85 German PD patients and 85 ethnically matched controls f...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Klein C,Vieregge P,Hagenah J,Sieberer M,Doyle E,Jacobs H,Gasser T,Breakefield XO,Risch NJ,Ozelius LJ

    更新日期:1999-07-01 00:00:00

  • Disease-Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients.

    abstract::Variants in the ATL1 gene have been repeatedly described as the second most frequent cause of hereditary spastic paraplegia (HSP), a motor neuron disease manifested by progressive lower limb spasticity and weakness. Variants in ATL1 have been described mainly in patients with early onset HSP. We performed Sanger seque...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Mészárosová AU,Grečmalová D,Brázdilová M,Dvořáčková N,Kalina Z,Čermáková M,Vávrová D,Smetanová I,Staněk D,Seeman P

    更新日期:2017-11-01 00:00:00

  • Further characterization of the human fumarase variant, FH 2--1.

    abstract::1. Further investigation of fumarase using lymphoblastoid cells derived from an individual of the FH 2--1 phenotype has confirmed that the mitochondrial (FHM) and soluble (FHS) forms of fumarase are determined at the same structural locus. 2. The FH 2--1 variant is associated with enzyme deficiency: c. 70% of normal i...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Edwards YH,Hopkinson DA

    更新日期:1979-10-01 00:00:00

  • The complex and diversified mitochondrial gene pool of Berber populations.

    abstract::The mitochondrial DNA variation of 295 Berber-speakers from Morocco (Asni, Bouhria and Figuig) and the Egyptian oasis of Siwa was evaluated by sequencing a portion of the control region (including HVS-I and part of HVS-II) and surveying haplogroup-specific coding region markers. Our findings show that the Berber mitoc...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Coudray C,Olivieri A,Achilli A,Pala M,Melhaoui M,Cherkaoui M,El-Chennawi F,Kossmann M,Torroni A,Dugoujon JM

    更新日期:2009-03-01 00:00:00

  • The genetic structure of human populations studied through short insertion-deletion polymorphisms.

    abstract::In a landmark study Rosenberg et al. (2002) analyzed human genome diversity with 377 microsatellites in the HGDP-CEPH Genome Diversity Panel and reported that the populations were structured into five geographical regions: America, Sub-Saharan Africa, East Asia, Oceania and a cluster composed of Europe, the Middle Eas...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Bastos-Rodrigues L,Pimenta JR,Pena SD

    更新日期:2006-09-01 00:00:00

  • Exon deletion in the non-catalytic domain of eIF2Bepsilon due to a splice site mutation leads to infantile forms of CACH/VWM with severe decrease of eIF2B GEF activity.

    abstract::The CACH/VWM syndrome is an autosomal recessive leukodystrophy characterized by a broad spectrum of clinical presentations and by diffuse cavitary degeneration of the white matter on MRI. Mutations responsible for this disorder are missense or frameshift mutations occurring in the five genes (EIF2B1-5) that encode the...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Horzinski L,Gonthier C,Rodriguez D,Scherer C,Boespflug-Tanguy O,Fogli A

    更新日期:2008-05-01 00:00:00

  • Tracing quantitative measurements on human chromosomes in family studies.

    abstract::Statistical methods are developed for tracing quantitative measurements on human chromosomes from parents to offspring. Tests for transmission are briefly considered. ...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Lauder IJ

    更新日期:1977-07-01 00:00:00

  • A genome-wide association study of autism reveals a common novel risk locus at 5p14.1.

    abstract::Although autism is one of the most heritable neuropsychiatric disorders, its underlying genetic architecture has largely eluded description. To comprehensively examine the hypothesis that common variation is important in autism, we performed a genome-wide association study (GWAS) using a discovery dataset of 438 autis...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Ma D,Salyakina D,Jaworski JM,Konidari I,Whitehead PL,Andersen AN,Hoffman JD,Slifer SH,Hedges DJ,Cukier HN,Griswold AJ,McCauley JL,Beecham GW,Wright HH,Abramson RK,Martin ER,Hussman JP,Gilbert JR,Cuccaro ML,Haines JL

    更新日期:2009-05-01 00:00:00

  • Assignment of the human cardiac/slow skeletal muscle troponin C gene (TNNC1) between D3S3118 and GCT4B10 on the short arm of chromosome 3 by somatic cell hybrid analysis.

    abstract::We have determined the chromosomal location of the human cardiac/slow skeletal muscle troponin C gene (TNNC1) to the short arm of chromosome 3 using somatic cell hybrids. PCR-based analysis of a 'monochromosomal' hybrid panel identified the presence of the TNNC1 gene on human chromosome 3 and subsequent analysis of th...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Townsend PJ,Yacoub MH,Barton PJ

    更新日期:1997-07-01 00:00:00

  • Dystrophin nonsense mutations can generate alternative rescue transcripts in lymphocytes.

    abstract::Secondary alterations in splicing have been reported to produce semi-functional mRNA from several nonsense mutations in the dystrophin gene. Disruptions of exonic splicing enhancers by single nucleotide changes are thought to underlie such alterations. The precise frequencies of such nonsense mutation-dependent splici...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Nishiyama A,Takeshima Y,Zhang Z,Habara Y,Tran TH,Yagi M,Matsuo M

    更新日期:2008-11-01 00:00:00

  • Haplotype analysis of the human alpha2-HS glycoprotein (fetuin) gene.

    abstract::Alpha2-HS glycoprotein (AHSG), which is equivalent to fetuin in other species, is a protein found in human plasma. AHSG is polymorphic with two common alleles and many variants. To examine the intragenic haplotypes and their diversity at this locus, a contiguous genomic DNA sequence (10.3 kb) was analyzed in 20 sample...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Osawa M,Yuasa I,Kitano T,Henke J,Kaneko M,Udono T,Saitou N,Umetsu K

    更新日期:2001-01-01 00:00:00

  • High resolution T association tests of complex diseases based on family data.

    abstract::This paper proposes family based Hotelling's T(2) tests for high resolution linkage disequilibrium (LD) mapping or association studies of complex diseases. Assume that genotype data of multiple markers or haplotype blocks are available for a sample of nuclear families, in which some offspring are affected. Paired Hote...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Fan R,Knapp M,Wjst M,Zhao C,Xiong M

    更新日期:2005-03-01 00:00:00

  • Linkage analysis and family classification under heterogeneity.

    abstract::Heterogeneity of the recombination fraction may or may not involve a mixture of two groups of elements. For the mixture situation (families with or without linkage between two gene loci), Morton's homogeneity test is compared with another test (Admixture test) with respect to significance level, power, parameter estim...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Ott J

    更新日期:1983-10-01 00:00:00

  • A speculative model for the Rh blood groups.

    abstract::Two closely linked structural loci, D and 'CcEe', are proposed as the basis of the Rh blood groups. Mutation and unequal crossing-over between the two loci at meiosis are considered as possible explanations for some rare Rh complexes. The theory predicts that complexes arising from unequal crossing-over would be expec...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Tippett P

    更新日期:1986-07-01 00:00:00

  • Assignment of the human locus determining phosphoglycolate phosphatase (PGP) to chromosome 16.

    abstract::The segregation of human phosphoglycolate phosphatase has been studied in 52 independent human-rodent hybrids and 69 subclones. The results suggest that human PGP is on chromosome 16. Family data suggest that PGP is not close to 16qh or alpha Hp. The most likely regional assignment for PGP would appear to be 16p13 or ...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Povey S,Jeremiah SJ,Barker RF,Hopkinson DA,Robson EB,Cook PJ,Solomon E,Bobrow M,Carritt B,Buckton KE

    更新日期:1980-01-01 00:00:00

  • Case-parent triads: estimating single- and double-dose effects of fetal and maternal disease gene haplotypes.

    abstract::Case-parent triad data are considered a robust basis for studying association between variants of a gene and a disease. Methods evaluating statistical significance of association, like the TDT-test and its extensions, are frequently used. When there are prior hypotheses of a causal effect of the gene under study, howe...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Gjessing HK,Lie RT

    更新日期:2006-05-01 00:00:00

  • G-protein beta-3 subunit C825T polymorphism, sodium and arterial blood pressure: a community-based study of Japanese men and women.

    abstract::Epidemiological evidence on gene-environment effects of the G-protein beta-3 subunit C825T polymorphisms and sodium on blood pressure in the free-living general population is limited. We examined the associations between the C825T polymorphism and blood pressure levels, stratified by the sodium variables estimated by ...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Yamagishi K,Tanigawa T,Cui R,Tabata M,Ikeda A,Yao M,Shimamoto T,Iso H

    更新日期:2006-11-01 00:00:00

  • Common variants in KCNQ1 confer increased risk of type 2 diabetes and contribute to the diabetic epidemic in East Asians: a replication and meta-analysis.

    abstract::We aimed to evaluate the effect of four common variants (rs2237892, rs2283228, rs2237895, and rs2237897) in KCNQ1 on susceptibility of type 2 diabetes (T2D) by performing a case-control study as well as a comprehensive meta-analysis. We genotyped these four variants in two sets of Chinese Han population, comprising a ...

    journal_title:Annals of human genetics

    pub_type: 杂志文章,meta分析


    authors: Wang H,Miao K,Zhao J,Liu L,Cui G,Chen C,Wang DW,Ding H

    更新日期:2013-09-01 00:00:00

  • Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia.

    abstract::A genome-wide association study of serum uric acid (SUA) laevels was performed in a relatively isolated population of European descent from an island of the Adriatic coast of Croatia. The study sample included 532 unrelated and 768 related individuals from 235 pedigrees. Inflation due to relatedness was controlled by ...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Karns R,Zhang G,Sun G,Rao Indugula S,Cheng H,Havas-Augustin D,Novokmet N,Rudan D,Durakovic Z,Missoni S,Chakraborty R,Rudan P,Deka R

    更新日期:2012-03-01 00:00:00

  • Homozygous sequence variants in the NPR2 gene underlying Acromesomelic dysplasia Maroteaux type (AMDM) in consanguineous families.

    abstract::Acromesomelic dysplasia Maroteaux type (AMDM) is an autosomal recessive skeletal disorder characterized by disproportionate short stature with shortening of the acromesomelic sections of the limbs. AMDM is caused by mutations in the NPR2 gene located on chromosome 9p21-p12. The gene encodes the natriuretic peptide rec...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Irfanullah,Umair M,Khan S,Ahmad W

    更新日期:2015-07-01 00:00:00

  • Evaluation of a restricted likelihood ratio test for mapping quantitative trait loci with extreme discordant sib pairs.

    abstract::Risch and Zhang recently proposed to use extreme discordant sib pairs for mapping quantitative trait loci. Here, it is shown that the set of genetically possible distributions of the number of marker alleles in such sib-pairs is described by two inequalities. Thus, a likelihood ratio test analogous to Holmans's possib...

    journal_title:Annals of human genetics

    pub_type: 杂志文章


    authors: Knapp M

    更新日期:1998-01-01 00:00:00