Cited by 1,126Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsGenetic and phenotypic traits in livestock

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A General Test of Association for Quantitative Traits in Nuclear Families

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Abecasis, G.R., Cardon, L.R., Cookson, W.O.C.·2000·The American Journal of Human Genetics

DOI 10.1086/302698PMC PMC1288332

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Abstract

High-resolution mapping is an important step in the identification of complex disease genes. In outbred populations, linkage disequilibrium is expected to operate over short distances and could provide a powerful fine-mapping tool. Here we build on recently developed methods for linkage-disequilibrium mapping of quantitative traits to construct a general approach that can accommodate nuclear families of any size, with or without parental information. Variance components are used to construct a test that utilizes information from all available offspring but that is not biased in the presence of linkage or familiality. A permutation test is described for situations in which maximum-likelihood estimates of the variance components are biased. Simulation studies are used to investigate power and error rates of this approach and to highlight situations in which violations of multivariate normality assumptions warrant the permutation test. The relationship between power and the level of linkage disequilibrium for this test suggests that the method is well suited to the analysis of dense maps. The relationship between power and family structure is investigated, and these results are applicable to study design in complex disease, especially for late-onset conditions for which parents are usually not available. When parental genotypes are available, power does not depend greatly on the number of offspring in each family. Power decreases when parental genotypes are not available, but the loss in power is negligible when four or more offspring per family are genotyped. Finally, it is shown that, when siblings are available, the total number of genotypes required in order to achieve comparable power is smaller if parents are not genotyped.

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“edu/csg/abecasis/QTDT), which is based on a variance-components framework [24].”
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“SpeciWcally, we used two tests: the family-based association test, FBAT proposed by (Horvath et al. 2001) and implemented in the FBAT program and the orthogonal test (OT) proposed by (Abecasis et al. 2000) and included in the QTDT program.”
Method
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Scerri, T. S., Darki, F., Newbury, D. F., Whitehouse, A., Peyrard‐Janvid, M., Matsson, H., Ang, Q. W., Pennell, C. E., Ring, S. M., Stein, J. F., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050321 · Cited by 41
“Family-based cohorts were analysed using QTDT [63].”
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“We compare the achieved power levels of the proposed overall family-based association test, Zi, with the weighting approach by Ionita-Laza et al [12], the original VanSteen approach [11], the QTDT approach [28] and population-based analysis, i.”
Influential
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“Zhang et al. (2003) found that mapping precision for a variance components analysis (Abecasis et al. 2000) of marker association with immunoglobulin E levels was similar when using single markers compared to using haplotypes of three, four or five markers.”
Method
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“For a nuclear family, the expected number of copies of a specific allele can be specified based on the genotypes of the parents according to Mendel’s law, if they are typed [Abecasis et al., 2000; Liu et al., 2002]. In addition to the marginal effect of a marker as in this example, gene-gene and geneenvironment intera…”
MethodInfluential
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Method
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“for analysis of small samples and non-normal data ( Abecasis et al. 2000 ).”
Background
Meprin β metalloprotease gene polymorphisms associated with diabetic nephropathy in the Pima Indians
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“To conduct a family-based test of within-family association in discordant siblings, a modification of the method of Abecasis et al. (2000) was used; the method tested for association under an additive genetic model.”
Method
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“was used where the associations are partitioned into between- and within-family components (31); for the present analyses, these components were represented, respectively, by the mean number of risk alleles for the sibship and each individual’s departure from this mean.”
Method
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“Association analyseswith the quantitative phenotype scores were done using the QTDT procedure [Abecasis et al., 2000] with empirical significance values calculated through 1,000 permutations,while theFBATprocedure [Horvath et al., 2001] was used for the dichotomous affected trait.”
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“Moreover, the between/within model can be readily extended to allow for multiple alleles, such as microsatellites, or multiple nearby polymorphisms , such as specific haplotypes (Fulker et al., 1999; Abecasis et al., 2000).”
BackgroundInfluentialSelf-citation
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“(25) was used to partition the association between or within sibship components.”
Method
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“10,11 Fam-ily-based approaches, such as FBAT, 11 that restrict analysis to the within-family component of association by conditioning on relatives’ genotypes, provide robustness to population structure at the price of strong requirements on the availability of genotype data on relatives in order to…”
Method
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“E regression method (47) using Genehunter (48) and the VC method (49) using QTDT and MERLIN (50,51).”
Method
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“In this process, Q as the fixed effect measures population structure that is calculated by package Structure [11], K as the random effect detects the relative kinship matrix that empirically measures the genetical similarity across individuals from markers or SNPs and computed by SPAGeDi [40].”
Method
Linear models for joint association and linkage QTL mapping
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“Conversely, the QTDT has no need of PDQ calculation or - possibly - map ordering of SNPs.”
BackgroundMethodInfluential
Characteristics of a spina bifida population including North American Caucasian and Hispanic individuals
Au, K. S., Tran, P. X., Tsai, C. C., O'Byrne, M. R., Lin, J., Morrison, A. C., Hampson, A. W., Cirino, P. T., Fletcher, J. M., Ostermaier, K. K., et al. (2008) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20499 · Cited by 39
“To analyze quantitative phenotypes, we used quantitative-TDT (Abecasis et al., 2000).”
Method
Genotype at the −174G/C Polymorphism of the Interleukin-6 Gene Is Associated With Common Carotid Artery Intimal-Medial Thickness
Mayosi, B. M., Avery, P. J., Baker, M., Gaukrodger, N., Imrie, H., Green, F. R., Farrall, M., Watkins, H. C., & Keavney, B. D. (2005) · Stroke · doi:10.1161/01.str.0000182254.47941.96 · Cited by 39
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“A number of approaches that incorporate quantitative phenotypes into the TDT analysis have been developed (Allison 1997; Rabinowitz 1997; Waldman et al. 1999) and have been implemented in available software programs (Abecasis et al. 2000; Lake et al. 2000).”
Method
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“Significant transmission distortion was seen for allele 6, with lymphocyte count and CD4 T cell level indicating association in the presence of linkage (table 6) (Abecasis et al. 2000; Martin et al. 2000).”
Background
Evidence for a Major Quantitative Trait Locus on Chromosome 17q21 Affecting Low-Density Lipoprotein Peak Particle Diameter
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“Tests of association with the quantitative traits were performed in a variance components framework using the QTDT program ( 56 ).”
BackgroundMethodSelf-citation
High-Density Linkage Map and QTLs for Growth in Snapper ( Chrysophrys auratus )
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The R563Q mutation of the epithelial sodium channel beta-subunit is associated with hypertension : cardiovascular topics
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Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families
Liu, Y., Rocha-Sanchez, S. M., Liu, P.-Y., Long, J., Lü, Y., Elze, L., Recker, R. R., & Deng, H. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00213.2003 · Cited by 38
“(1) was adopted in the analyses, where the genotype score is decomposed into orthogonal between-family ( b) and within-family ( w) components.”
Influential
Suggestive evidence of association of C-159T functional polymorphism of the CD14 gene with atopic asthma in northern and northwestern Indian populations
Sharma, M., Batra, J., Mabalirajan, U., Goswami, S., Ganguly, D., Lahkar, B., Bhatia, N. K., Kumar, A., & Ghosh, B. (2004) · Immunogenetics · doi:10.1007/s00251-004-0721-y · Cited by 38
“C-159T polymorphism and log10 tsIgE levels, using a QTDT program that can accommodate nuclear families of any size, with or without parental genotype data (Abecasis et al. 2000).”
MethodInfluential
Estrogen Receptor α Gene Polymorphisms and Peak Bone Density in Chinese Nuclear Families
Qin, Y.-J., Shen, H., Huang, Q.-R., Zhao, L.-J., Zhou, Q., Li, M., He, J.-W., Mo, X., Lu, J.-H., Recker, R. R., et al. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.6.1028 · Cited by 38
“These tests were all developed under a variance component framework and have been implemented in a program QTDT((41,42)) (for quantitative trait locus transmission disequilibrium test), which is available on the internet (http://www.”
Influential
A genome scan for Plasmodium falciparum malaria identifies quantitative trait loci on chromosomes 5q31, 6p21.3, 17p12, and 19p13
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“1 program [18].”
Distinct Loci in the CHRNA5/CHRNA3/CHRNB4 Gene Cluster Are Associated With Onset of Regular Smoking
Stephens, S. H., Hartz, S. M., Hoft, N. R., Saccone, N. L., Corley, R., Hewitt, J. K., Hopfer, C. J., Breslau, N., Coon, H. H., Chen, X., et al. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21760 · Cited by 41
“The QFAM total association test (–qfam-total) was used to conduct a family-based analysis that partitions the between family variance and the within family variance [Fulker et al., 1999] and is similar to that incorporated in the QTDT package [Abecasis et al., 2000].”
Method
Complex effects of dyslexia risk factors account for ADHD traits: evidence from two independent samples
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“In order to assign items to factors, only the items with a loading of 0.40 or greater were taken into account. The factor solution was then rotated (using the VARIMAX procedure)and factor scores calculated using regression. All factors have eigenvalues >1.0, indicating that they account for more variance than any sing…”
MethodInfluential
Nested Association Mapping for Identification of Functional Markers
Guo, B., Sleper, D. A., & Beavis, W. D. (2010) · Genetics · doi:10.1534/genetics.110.115782 · Cited by 37
“The data analysis method proposed herein has the following distinctive features from these other approaches: (1) Background QTL are controlled with cofactor markers identified in a model-building process, whereas they are controlled with a covariance matrix based on family relationships in QTDT (Abecasis et al. 2000)…”
Genetic Variation at the Proprotein Convertase Subtilisin/Kexin Type 5 Gene Modulates High-Density Lipoprotein Cholesterol Levels
Iatan, I., Dastani, Z., Do, R., Weissglas‐Volkov, D., Ruel, I. L., Lee, J. C., Huertas‐Vázquez, A., Taskinen, M., Prat, A., Seidah, N. G., et al. (2009) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.109.877811 · Cited by 38
Association between a vasopressin receptor AVPR1A promoter region microsatellite and eating behavior measured by a self‐report questionnaire (Eating Attitudes Test) in a family‐based study of a nonclinical population
Bachner‐Melman, R., Zohar, A. H., Elizur, Y., Nemanov, L., Gritsenko, I., Konis, D., & Ebstein, R. P. (2004) · International Journal of Eating Disorders · doi:10.1002/eat.20049 · Cited by 38
Quantitative Trait Linkage Analysis Using Gaussian Copulas
Li, M., Boehnke, M., Abecasis, G. R., & Song, P. X. ‐. (2006) · Genetics · doi:10.1534/genetics.105.054650 · Cited by 37
“Our results suggest that the copula VC method could be used to improve power of the association tests in the quantitative trait transmission/disequilibrium test (Abecasis et al. 2000), which incorporates the tested markers as covariates in a standard VC model that assumes multivariate normality.”
Self-citation
Association of peripheral and central arterial wave reflections with the CYP11B2 ???344C allele and sodium excretion
Wojciechowska, W., Staessen, J. A., Stolarz, K., Nawrot, T. S., Filipovsk, J., Tich, M., Bianchi, G., Brand, E., Cwynar, M., Grodzicki, T. K., et al. (2004) · Journal of Hypertension · doi:10.1097/00004872-200412000-00013 · Cited by 37
Linkage and Linkage Disequilibrium Mapping of Genes Influencing Human Obesity in Chromosome Region 7q22.1–7q35
Li, W., Li, D., Wang, S., Zhang, S., Zhao, H., & Price, R. A. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1557 · Cited by 37
“Empirical P values were computed by QTDT based on a 1,000-replicates simulation.”
BackgroundMethodInfluential
GWAS analysis using interspecific backcross progenies reveals superior blue catfish alleles responsible for strong resistance against enteric septicemia of catfish
Tan, S., Zhou, T., Wang, W., Jin, Y., Wang, X., Geng, X., Luo, J., Yuan, Z., Yang, Y., Shi, H., et al. (2018) · Molecular Genetics and Genomics · doi:10.1007/s00438-018-1443-4 · Cited by 36
Whole-genome studies identify solute carrier transporters in cellular susceptibility to paclitaxel
Njiaju, U. O., Gamazon, E. R., Gorsic, L. K., Delaney, S. M., Wheeler, H. E., Im, H. K., & Dolan, M. E. (2012) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328352f436 · Cited by 36
Population-specific GSTM1 copy number variation
Huang, R. S., Chen, P., Wisel, S., Duan, S., Zhang, W., Cook, E. H., Das, S., Cox, N. J., & Dolan, M. E. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn345 · Cited by 36
Epistatic interaction between α- and γ-adducin influences peripheral and central pulse pressures in white Europeans
Cwynar, M., Staessen, J. A., Tichá, M., Nawrot, T. S., Citterio, L., Kuznetsova, T., Wojciechowska, W., Stolarz, K., Filipovský, J., Kawecka−Jaszcz, K., et al. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000166836.70935.e7 · Cited by 35
Association analysis of dyslexia candidate genes in a Dutch longitudinal sample
Carrión-Castillo, A., Maassen, B., Franke, B., Heister, A. J. G. A. M., Naber, M., van der Leij, A., Francks, C., & Fisher, S. E. (2017) · European Journal of Human Genetics · doi:10.1038/ejhg.2016.194 · Cited by 35
A Rapid Generalized Least Squares Model for a Genome-Wide Quantitative Trait Association Analysis in Families
Li, X., Basu, S., Miller, M. B., Iacono, W. G., & McGue, M. K. (2011) · Human Heredity · doi:10.1159/000324839 · Cited by 35
“(6) QTDT: The orthogonal association test under an allelic transmission scoring model in extended pedigrees by Abecasis et al. [16] was carried out using the QTDT software.”
Method
Differences in genetic architecture between continents at a major locus previously associated with sea age at sexual maturity in European Atlantic salmon
Boulding, E. G., Ang, K. P., Elliott, J. A. K., Powell, F., & Schaeffer, L. R. (2018) · Aquaculture · doi:10.1016/j.aquaculture.2018.09.025 · Cited by 34
Catechol-o-Methyltransferase Genotype and Childhood Trauma May Interact to Impact Schizotypal Personality Traits
Savitz, J. B., van der Merwe, L., Newman, T. K., Stein, D. J., & Ramesar, R. (2009) · Behavior Genetics · doi:10.1007/s10519-009-9323-7 · Cited by 34
Titin is a candidate gene for stroke volume response to endurance training: the HERITAGE Family Study
Rankinen, T., Rice, T., Boudreau, A., Leon, A. S., Skinner, J. S., Wilmore, J. H., Rao, D. C., & Bouchard, C. (2003) · Physiological Genomics · doi:10.1152/physiolgenomics.00147.2002 · Cited by 34
“Transmission/disequilibrium tests (TDT) among the microsatellite markers were performed using variance-components-based orthogonal model as implemented in the QTDT software package ( 1 ).”
Method
Combined Linkage and Association Tests in Mx
Posthuma, D., de Geus, E. D., Boomsma, D., & Neale, M. (2004) · Behavior Genetics · doi:10.1023/b:bege.0000013732.19486.74 · Cited by 32
“…some other gene within that genomic region, that not all relevant alleles of that locus have been genotyped, or that (part of) the observed linkage may have been artefactual (i.e., because of marker genotype errors) (Abecasis et al., 2000, 2001; Cardon and Abecasis, 2000; McKenzie et al., 2001).”
BackgroundInfluential
CHRNB2 promoter region: association with subjective effects to nicotine and gene expression differences
Hoft, N. R., Stitzel, J. A., Hutchison, K. E., & Ehringer, M. A. (2010) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2010.00650.x · Cited by 38
“QTDT was subsequently used to verify the results (Abecasis et al. 2000).”
Epigenetic Regulation in Particulate Matter-Mediated Cardiopulmonary Toxicities: A Systems Biology Perspective
Wang, T., Garcia, J. G. N., & Zhang, W. (2012) · Current pharmacogenomics and personalized medicine (Online)/Current pharmacogenomics and personalized medicine · doi:10.2174/187569212803901792 · Cited by 35
“The methylation profiles then can be deduced by techniques such as direct sequencing [99, 100], pyrosequencing [101] or microarray-based approaches [102].”
Method
Heritability and genome-wide SNP linkage analysis of temperament in bipolar disorder
Greenwood, T. A., Badner, J. A., Byerley, W., Keck, P. E., McElroy, S. L., Remick, R. A., Sadovnick, A. D., Akiskal, H. S., & Kelsoe, J. R. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.05.035 · Cited by 34
“study used QTDT to estimate heritability as part of a genetic association analysis, we have used the variance components method in SOLAR for this purpose (Abecasis et al., 2000; Almasy and Blangero, 1998).”
Method
A genetic study of ADHD and activity level in infancy
Ilott, N. E., Saudino, K. J., Wood, A. C., & Asherson, P. J. (2009) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2009.00560.x · Cited by 35
“The AP test of association in QTDT compares the within and between components of association and thus provides a test for stratification.”
MethodInfluential
Prioritization of Positional Candidate Genes Using Multiple Web-Based Software Tools
Thornblad, T., Elliott, K., Jowett, J. B. M., & Visscher, P. M. (2007) · Twin Research and Human Genetics · doi:10.1375/twin.10.6.861 · Cited by 33
“The traditional approach to reduce the number of candidate genes is by fine-mapping studies using more markers and pedigrees (e.g., Glazier et al., 2002), followed by population-wide linkage disequilibrium studies (e.g., Abecasis et al., 2000).”
BackgroundMethod
A Candidate Gene Association Study of Alcohol Consumption in Young Women*
Arpana Agrawal, A., Lynskey, M. T., Todorov, A. A., Schrage, A. J., Littlefield, A. K., Grant, J. D., Zhu, Q., Nelson, E. C., Madden, P. A. F., Bucholz, K. K., et al. (2010) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01372.x · Cited by 33
“Key Words: Alcohol Consumption, Genes, QTDT.”
Method
Variants in the gene encoding aldose reductase (AKR1B1) and diabetic nephropathy in American Indians
Wolford, J. K., Yeatts, K. A., Eagle, A. R., Nelson, R. G., Knowler, W. C., & Hanson, R. L. (2006) · Diabetic Medicine · doi:10.1111/j.1464-5491.2006.01834.x · Cited by 33
CREB1 Is a Strong Genetic Predictor of the Variation in Exercise Heart Rate Response to Regular Exercise
Rankinen, T., Argyropoulos, G. A., Rice, T., Rao, D. C., & Bouchard, C. (2010) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.109.925644 · Cited by 33
A Genome-Wide Linkage and Association Scan Reveals Novel Loci for Hypertension and Blood Pressure Traits
Guo, Y., Tomlinson, B., Chu, T. T. W., Fang, Y. J., Gui, H., Tang, C. S.-M., Yip, B. H. K., Cherny, S. S., Hur, Y., Sham, P. C., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031489 · Cited by 33
“We also employed QTDT [26] to conduct a combined test of linkage and association, which can help determine whether a putative QTL locus detected via association is the actual diseasecausing locus or whether it is merely in disequilibrium with the trait locus [27,28].”
Replication of GWAS of bipolar disorder: association of SNPs near CDH7 with bipolar disorder and visual processing
Soronen, P., Ollila, H. M., Antila, M., Silander, K., Palo, O. M., Kieseppä, T., Lönnqvist, J. K., Peltonen, L., Tuulio‐Henriksson, A., Partonen, T., et al. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.86 · Cited by 33
A new test for family-based association mapping with inbred lines from plant breeding programs
Stich, B., Melchinger, A. E., Piepho, H., Heckenberger, M., Maurer, H. P., & Reif, J. C. (2006) · Theoretical and Applied Genetics · doi:10.1007/s00122-006-0372-5 · Cited by 33
“The QIPDT extends the QPDT, a family-based association test developed in the context of human genetics, which is in contrast to the quantitative transmission disequilibrium test (Abecasis et al. 2000) a valid test of association in the presence of linkage when some of the nuclear families are related (Zhang et al.”
MethodResult
Functional UQCRC1 Polymorphisms Affect Promoter Activity and Body Lipid Accumulation
Kunej, T., Wang, Z., Michal, J. J., Daniels, T. F., Magnuson, N. S., & Jiang, Z. (2007) · Obesity · doi:10.1038/oby.2007.344 · Cited by 33
“The polymorphic site g.13487C T showed an extremely significant association with the trait (p 0.0001 for both GLM and QTDT; Table 1).”
MethodInfluential
Integrating epigenomics into pharmacogenomic studies
Zhang, W., Dolan, & Huang (2008) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s4341 · Cited by 33
“Given the critical role played by DNA methylation in gene regulation and the fact that DNA methylation is currently the most studied epigenetic system, we suggest that profi ling the variation in DNA methylation in the HapMap samples will provide new insights into the regulation of gene expression…”
Background
Human Genetics of Common Mycobacterial Infections
Remus, N., Alcaïs, A., & Abel, L. (2003) · Immunologic Research · doi:10.1385/ir:28:2:109 · Cited by 33
Single Nucleotide Polymorphisms in Monocyte Chemoattractant Protein-1 and Its Receptor Act Synergistically to Increase the Risk of Carotid Atherosclerosis
Nyquist, P., Winkler, C. A., McKenzie, L. M., Yanek, L. R., Becker, L. C., & Becker, D. M. (2009) · Cerebrovascular Diseases · doi:10.1159/000223437 · Cited by 32
“Bivariate analyses using standard χ 2 analysis were performed to discern any apparent associations between individual SNPs and carotid atherosclerosis. We then constructed haplotypes with the 4 chosen MCP-1 SNPs and conducted a bivariate analysis comparing individual haplotypes with carotid atherosclerosis. Multivaria…”
Method
A genome-wide scan in forty large pedigrees with multiple sclerosis
Willer, C. J., Dyment, D. A., Cherny, S. S., Ramagopalan, S. V., Herrera, B. M., Morrison, K., Sadovnick, A. D., RISCH, N. J., & Ebers, G. C. (2007) · Journal of Human Genetics · doi:10.1007/s10038-007-0194-6 · Cited by 32
“Analysis of transmission distortion using the QTDT package (Abecasis et al. 2000) revealed no evidence for significant association between MS affection status and autosomal microsatellite markers (n = 378) after adjusting Table 1 Regions of the genome-wide linkage scan implicated by multipoint HLOD analysis (HLOD [ 0.”
Method
The G Protein–Coupled Receptor Kinase 4 Gene Affects Blood Pressure in Young Normotensive Twins
Zhu, H., LU, Y., WANG, X., Treiber, F. A., HARSHFIELD, G., Snieder, H., & DONG, Y. (2006) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2005.07.007 · Cited by 32
Resting metabolic rate and respiratory quotient: results from a genome-wide scan in the Quebec Family Study
Jacobson, P., Rankinen, T., Tremblay, A., Përusse, L., Chagnon, Y. C., & Bouchard, C. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.6.1527 · Cited by 32
Variants in ARHGEF11, a Candidate Gene for the Linkage to Type 2 Diabetes on Chromosome 1q, Are Nominally Associated With Insulin Resistance and Type 2 Diabetes in Pima Indians
Ma, L., Hanson, R. L., Que, L. N., Cali, A. M. G., Fu, M., Mack, J. L., Infante, A. M., Kobes, S., Bogardus, C., Shuldiner, A. R., et al. (2007) · Diabetes · doi:10.2337/db06-0640 · Cited by 32
Association analysis of monoamine genes with measures of depression and anxiety in a selected community sample of siblings
Nash, M. W., Sugden, K., Huezo-Diaz, P., Williamson, R. J., Sterne, A., Purcell, S., Sham, P. C., & Craig, I. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30063 · Cited by 32
“Statistical analysiswasperformedusingQTDTversion 2.3.0 [Abecasis et al., 2000a].”
MethodInfluential
Genome-wide association study reveals growth-related markers and candidate genes for selection in Chinese longsnout catfish (Leiocassis longirostris)
Mou, C.-Y., Li, Y., Zhou, J. T., Li, Q., Zhou, B., Wei, Z., Luo, H., Ke, H., Duan, Y., Zhai, W.-T., et al. (2022) · Aquaculture · doi:10.1016/j.aquaculture.2022.738513 · Cited by 31
Polymorphisms in IL10 are associated with total Immunoglobulin E levels and Schistosoma mansoni infection intensity in a Brazilian population
Grant, A. V., Araújo, M. I., Ponte, E. V., Oliveira, R. R., Cruz, Á. A., Barnes, K. C., & Beaty, T. H. (2010) · Genes and Immunity · doi:10.1038/gene.2010.50 · Cited by 31
Interleukin 10 polymorphisms in ankylosing spondylitis
Goedecke, V., Crane, A. M., Jaakkola, E., Kaluza, W., Laiho, K., Weeks, D. E., Wilson, J., Kauppi, M. J., Kaarela, K., Tuomilehto, J., et al. (2003) · Genes and Immunity · doi:10.1038/sj.gene.6363930 · Cited by 31
Single nucleotide polymorphisms in JAZF1 and BCL11A gene are nominally associated with type 2 diabetes in African-American families from the GENNID study
Langberg, K. A., Ma, L., Sharma, N. K., Hanis, C. L., Elbein, S. C., Hasstedt, S. J., & Das, S. K. (2011) · Journal of Human Genetics · doi:10.1038/jhg.2011.133 · Cited by 32
Univariate/Multivariate Genome-Wide Association Scans Using Data from Families and Unrelated Samples
Zhang, L., Pei, Y., Li, J., Papasian, C. J., & Deng, H. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006502 · Cited by 31
“The application of transmission disequilibrium tests (TDT) [13], and its various extensions to a variety of genetic models for both quantitative [14–19] and qualitative traits [20–24], form the basis of family-based association tests.”
Blood pressure and urinary sodium excretion in relation to the A-1984G adrenomedullin polymorphism in a Chinese population
Li, Y., Staessen, J. A., Li, L., Gao, P., Thijs, L., Brand, E., Brand-Herrmann, S.-M., Zhu, D., & Wang, J.-G. (2006) · Kidney International · doi:10.1038/sj.ki.5000213 · Cited by 31
Mapping Heritability and Molecular Genetic Associations With Cortical Features Using Probabilistic Brain Atlases: Methods and Applications to Schizophrenia
Cannon, T. D., Thompson, P. M., van Erp, T. G. M., HUTTUNEN, M. O., Lönnqvist, J. K., Kaprio, J. A., & Toga, A. W. (2006) · Neuroinformatics · doi:10.1385/ni:4:1:5 · Cited by 31
Variants in the Cav2.3 (α1E) Subunit of Voltage-Activated Ca2+ Channels Are Associated With Insulin Resistance and Type 2 Diabetes in Pima Indians
Muller, Y. L., Hanson, R. L., Zimmerman, C. T., Harper, I., Sutherland, J. R., Kobes, S., Knowler, W. C., Bogardus, C., & Baier, L. J. (2007) · Diabetes · doi:10.2337/db07-0587 · Cited by 31
Power Calculations Using Exact Data Simulation: A Useful Tool for Genetic Study Designs
van der Sluis, S., Dolan, C., Neale, M., & Posthuma, D. (2007) · Behavior Genetics · doi:10.1007/s10519-007-9184-x · Cited by 35
Association of AKT1 with verbal learning, verbal memory, and regional cortical gray matter density in twins
Pietiläinen, O. P. H., Paunio, T., Loukola, A., Tuulio‐Henriksson, A., Kieseppä, T., Thompson, P. M., Toga, A. W., van Erp, T. G. M., Silventoinen, K., Soronen, P., et al. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30890 · Cited by 31
“The genetic influence of AKT1 on gray matter density at each cortical voxel was assessed using QTDT software [Abecasis et al., 2000a,b].”
Method
Family‐based association study of the serotonin transporter gene polymorphisms in Korean ADHD trios
Kim, S., Badner, J. A., Cheon, K.-A. A., Kim, B., Yoo, H., Kim, S. J., Cook, E. H., LEVENTHAL, B. L., & Kim, Y. S. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30214 · Cited by 32
“QTDT incorporates variance components methodology in the analysis of family data and includes exact estimation of P-values for analysis of small samples and non-normal data [Abecasis et al., 2000].”
Method
Type 2 diabetes susceptibility single-nucleotide polymorphisms are not associated with polycystic ovary syndrome
Ewens, K. G., Jones, M. R., Ankener, W., Stewart, D. R., Urbanek, M., Dunaif, A. E., Legro, R. S., Chua, A. K., Azziz, R., Spielman, R. S., et al. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.02.050 · Cited by 30
The MTHFR gene polymorphism is associated with lean body mass but not fat body mass
Liu, X., Zhao, L.-J., Liu, Y., Xiong, D.-H., Recker, R. R., & Deng, H. (2008) · Human Genetics · doi:10.1007/s00439-007-0463-7 · Cited by 30
“The orthogonal model implemented in QTDT (v2.5.1) ( Abecasis et al. 2000 ) was adopted in the association analyses, where the total association of speciWc polymorphism with phenotype is decomposed into orthogonal betweenfamily (b) and within-family (w) components.”
MethodInfluential
The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits
Webster, R. J., Warrington, N. M., Weedon, M. N., Hattersley, A. T., McCaskie, P. A., Beilby, J. P., Palmer, L. J., & Frayling, T. M. (2008) · Diabetologia · doi:10.1007/s00125-008-1175-9 · Cited by 30

Authors: Abecasis, G. R., Cardon, L. R., & Cookson, W. O. C.
Affiliations: Centre for Human Genetics (GB)
Corresponding author: Abecasis, G.R.
ORCID: Abecasis, G.R.
Venue: The American Journal of Human Genetics
Publisher: Elsevier BV
Published: 2000-01
Volume: 66
Issue: 1
Pages: 279-292
ISSN: 0002-9297 (ISSN-L)
DOI: 10.1086/302698
PMC: PMC1288332
OpenAlex: W2078625752
Cited by: 1,126
References: 30
Citations by year: 2026: 2 · 2025: 3 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 13 · 2020: 15 · 2019: 13 · 2018: 18 · 2017: 23 · 2016: 22 · 2015: 26 · 2014: 27 · 2013: 38 · 2012: 51
FWCI: 27.12
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4948 d)
Locations: The American Journal of Human Genetics (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
Keywords: association mapping, quantitative traits, nuclear family, variance components, permutation tests, fine mapping, power analysis, family structure, parental genotypes, multivariate normality, research design
MeSH terms: Genetics, Population, Humans, Models, Genetic, Nuclear Family, Linkage Disequilibrium, Quantitative Trait, Heritable

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A General Test of Association for Quantitative Traits in Nuclear Families

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