Home About us Contact
|
Home About us Contact | ||
|
|
||
Pair Study (pair + study)
Selected AbstractsIdentification of Susceptibility Loci for Alcohol-Related Traits in the Irish Affected Sib Pair Study of Alcohol DependenceALCOHOLISM, Issue 11 2006Po-Hsiu Kuo Background: Alcoholism is a phenotypically and probably genetically heterogeneous condition. Thus, one strategy for finding genes influencing liability to alcoholism is to study the components of alcoholism, which may be more directly related to the underlying pathophysiology than is clinical diagnosis. The goal of this study was to identify genomic regions containing susceptibility loci for alcohol-related traits. Methods: A 4-cM dense whole-genome linkage study was conducted in the Irish Affected Sib Pair Study of Alcohol Dependence. Probands, affected siblings, and parents were evaluated by structured interview. Variance component linkage analysis was applied to data from 485 families for 5 measures: initial sensitivity and tolerance (based on scales from the self-report of the effects of ethanol; maximum drinks within 24 hours, an empirically derived factor score based on withdrawal symptoms, and age at onset of alcohol dependence. Results: Evidence for linkage (p<0.005) was found on 9 chromosomes. For age at onset, 2 regions were found on chromosome 9 (highest Lod=2.3, p=0.0005). For initial level of response to alcohol, suggestive regions were on chromosomes 1 and 11 (highest Lod=2.9, p=0.0001 on chromosome 11), while those for tolerance signals were on chromosomes 1, 6, and 22. Maximum drinking was associated with regions on chromosomes 12 and 18. For withdrawal symptoms, the highest peak was on chromosome 2 (Lod=2.2, p=0.0007). Conclusions: Using quantitative measures of components of alcohol dependence, we identified several regions of the genome that may contain susceptibility loci for specific alcohol-related traits and merit additional study. [source] Multipoint analysis using affected sib pairs: Incorporating linkage evidence from unlinked regionsGENETIC EPIDEMIOLOGY, Issue 2 2001Kung-Yee Liang Abstract In this paper, we proposed a multipoint method to assess evidence of linkage to one region by incorporating linkage evidence from another region. This approach uses affected sib pairs in which the number of alleles shared identical by descent (IBD) is the primary statistic. This generalized estimating equation (GEE) approach is robust in that no assumption about the mode of inheritance is required, other than assuming the two regions being considered are unlinked and that there is no more than one susceptibility gene in each region. The method proposed here uses data from all available families to simultaneously test the hypothesis of statistical interaction between regions and to estimate the location of the susceptibility gene in the target region. As an illustration, we have applied this GEE method to an asthma sib pair study (Wjst et al. [1999] Genomics 58:1,8), which earlier reported evidence of linkage to chromosome 6 but showed no evidence for chromosome 20. Our results yield strong evidence to chromosome 20 (P value = 0.0001) after incorporating linkage information from chromosome 6. Furthermore, it estimates with 95% certainty that the map location of the susceptibility gene is flanked by markers D20S186 and D20S101, which are approximately 16.3 cM apart. Genet. Epidemiol. 21:105,122, 2001. © 2001 Wiley-Liss, Inc. [source] Contribution of the LRP5 Gene to Normal Variation in Peak BMD in Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2005Daniel L Koller Abstract The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD. Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample. Introduction: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been implicated as the cause of multiple distinct BMD-related rare Mendelian phenotypes. We sought to examine whether the LRP5 gene contributes to the observed variation in peak BMD in the normal population. Materials and Methods: We genotyped 12 single nucleotide polymorphisms (SNPs) in LRP5 using allele-specific PCR and mass spectrometry methods. Linkage disequilibrium between the genotyped LRP5 SNPs was measured. We tested for association between these SNPs and both hip and spine BMD (adjusted for age and body weight) in 1301 healthy premenopausal women who took part in a sibling pair study aimed at identifying the genes underlying peak bone mass. Our study used both population-based (ANOVA) and family-based (quantitative transmission disequilibrium test) association methodology. Results and Conclusions: The linkage disequilibrium pattern and haplotype block structure within the LRP5 gene were consistent with that observed in other studies. Although significant evidence of association was found between LRP5 SNPs and both hip and spine BMD, only a small proportion of the total variation in these phenotypes was accounted for. The genotyped SNPs accounted for ,0.8% of the variation in femoral neck BMD and 1.1% of the variation in spine BMD. Results from our sample suggest that natural variation in and around LRP5 is not a major contributor to the observed variability in peak BMD at either the femoral neck or lumbar spine in white women. [source] | ||||||||||