This study will build upon existing sib-pair methods for multipoint mapping of QTLs. It will greatly expand upon the statistical methodology to identify and localize QTLs for complex traits by merging sib-pair methods with a powerful twin design which uses phenotypic data on MZ and DZ twins to resolve phenotypic variability into genetic and non-genetic components, and partition human quantitative genetic variation into effects due to loci on specific chromosomal regions. This quantitative methodology will be applied to risk factors for cardiovascular disease -- one of the most pressing health problems in Western society. Population-based samples of Dutch, Swedish, and Australian twins have been identified in previous studies, phenotypic measures on lipids, lipoproteins, and other important cardiovascular risk factors have been obtained, and blood has been banked in a valuable resource which is available for use in this proposed project. In 500 DZ twin pairs, a series of 175 highly polymorphic microsatellite markers will be detected using an automated process for detecting fluorescent signals. These data will be analyzed using the new statistical methods both to confirm the effects of a series of candidate loci and to test for the effects of previously unknown QTLs.
| van Beijsterveldt, Catherina E M; Middeldorp, Christel M; Slof-Op't Landt, Margarita C T et al. (2011) Influence of candidate genes on attention problems in children: a longitudinal study. Behav Genet 41:155-64 |
| Middeldorp, C M; Slof-Op 't Landt, M C T; Medland, S E et al. (2010) Anxiety and depression in children and adults: influence of serotonergic and neurotrophic genes? Genes Brain Behav 9:808-16 |
| Middeldorp, Christel M; Sullivan, Patrick F; Wray, Naomi R et al. (2009) Suggestive linkage on chromosome 2, 8, and 17 for lifetime major depression. Am J Med Genet B Neuropsychiatr Genet 150B:352-8 |
| Wray, Naomi R; Middeldorp, Christel M; Birley, Andrew J et al. (2008) Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands. Arch Gen Psychiatry 65:649-58 |
| Middeldorp, C M; Hottenga, J-J; Slagboom, P E et al. (2008) Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype. Mol Psychiatry 13:84-9 |
| Beekman, Marian; Posthuma, Danielle; Heijmans, Bastiaan T et al. (2004) Combined association and linkage analysis applied to the APOE locus. Genet Epidemiol 26:328-37 |
| Beekman, Marian; Heijmans, Bastiaan T; Martin, Nicholas G et al. (2003) Two-locus linkage analysis applied to putative quantitative trait loci for lipoprotein(a) levels. Twin Res 6:322-4 |
| Beekman, Marian; Heijmans, Bastiaan T; Martin, Nicholas G et al. (2003) Evidence for a QTL on chromosome 19 influencing LDL cholesterol levels in the general population. Eur J Hum Genet 11:845-50 |
| Beekman, Marian; Heijmans, Bastiaan T; Martin, Nicholas G et al. (2002) Heritabilities of apolipoprotein and lipid levels in three countries. Twin Res 5:87-97 |
| Beekman, M; Lakenberg, N; Cherny, S S et al. (2001) A powerful and rapid approach to human genome scanning using small quantities of genomic DNA. Genet Res 77:129-34 |
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