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Genome-wide scan linkage analysis for Parkinson's disease: the European genetic study of Parkinson's disease.

ABSTRACT: To undertake a full genome-wide screen for Parkinson's disease susceptibility loci.A genome-wide linkage study was undertaken in 227 affected sibling pairs from 199 pedigrees with Parkinson's disease. The pedigree sample consisted of 188 pedigrees from five European countries, and 11 from the USA. Individuals were genotyped for 391 microsatellite markers at approximately 10 cM intervals throughout the genome. Multipoint model-free affected sibling pair linkage analyses were carried out using the MLS (maximum LOD score) test.There were six chromosomal regions with maximum MLS peaks of 1 or greater (pointwise p<0.018). Four of these chromosomal regions appear to be newly identified regions, and the highest MLS values were obtained on chromosomes 11q (MLS = 1.60, at 91 cM, D11S4175) and 7p (MLS = 1.51, at 5 cM, D7S531). The remaining two MLS peaks, on 2p11-q12 and 5q23, are consistent with excess sharing in regions reported by other studies. The highest MLS peak was observed on chromosome 2p11-q12 (MLS = 2.04, between markers D2S2216 and D2S160), within a relatively short distance (approximately 17 cM) from the PARK3 region. Although a stronger support of linkage to this region was observed in the late age of onset subgroup of families, these differences were not significant. The peak on 5q23 (MLS = 1.05, at 130 cM, D5S471) coincides with the region identified by three other genome scans. All peak locations fell within a 10 cM distance.These stratified linkage analyses suggest linkage heterogeneity within the sample across the 2p11-q12 and 5q23 regions, with these two regions contributing independently to Parkinson's disease susceptibility.

SUBMITTER: Martinez M

PROVIDER: S-EPMC1735631 | biostudies-other | 2004 Dec

REPOSITORIES: biostudies-other

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Genome-wide scan linkage analysis for Parkinson's disease: the European genetic study of Parkinson's disease.

Martinez M M Brice A A Vaughan J R JR Zimprich A A Breteler M M B MM Meco G G Filla A A Farrer M J MJ Bétard C C Hardy J J De Michele G G Bonifati V V Oostra B B Gasser T T Wood N W NW Dürr A A

Journal of medical genetics 20041201 12

<h4>Objective</h4>To undertake a full genome-wide screen for Parkinson's disease susceptibility loci.<h4>Methods</h4>A genome-wide linkage study was undertaken in 227 affected sibling pairs from 199 pedigrees with Parkinson's disease. The pedigree sample consisted of 188 pedigrees from five European countries, and 11 from the USA. Individuals were genotyped for 391 microsatellite markers at approximately 10 cM intervals throughout the genome. Multipoint model-free affected sibling pair linkage a ...[more]

PMID: 15591275

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Project description:Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes.We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES). Plasma triglyceride values were transformed, and a variance-components technique was used to conduct multipoint linkage analysis.After adjusting for the significant effects of sex and BMI, heritability for plasma triglycerides was estimated as 46 +/- 7% (P < 0.0001). Multipoint linkage analysis yielded the strongest evidence for linkage of plasma triglycerides near marker D12S391 on chromosome 12p (logarithm of odds [LOD] = 2.4). Our linkage signal on chromosome 12p provides independent replication of a similar finding in another Mexican-American sample from the San Antonio Family Diabetes Study (SAFDS). Combined multipoint linkage analysis of the VAGES and SAFDS data yielded significant evidence for linkage of plasma triglycerides to a genetic location between markers GATA49D12 and D12S391 on 12p (LOD = 3.8, empirical P value = 2.0 x 10(-5)). This region on 12p harbors the gene-encoding adiponectin receptor 2 (AdipoR2), where we previously have shown that multiple single nucleotide polymorphisms are associated with plasma triglyceride concentrations in the SAFDS. In the present study, we provided suggestive evidence in favor of association for rs929434 with triglyceride concentrations in the VAGES.Collectively, these results provide strong evidence for a major locus on chromosome 12p that influences plasma triglyceride levels in Mexican Americans.

Dataset Information

Genome-wide scan linkage analysis for Parkinson's disease: the European genetic study of Parkinson's disease.

Publications

Genome-wide scan linkage analysis for Parkinson's disease: the European genetic study of Parkinson's disease.

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