scholarly journals Exploring causality via identification of SNPs or haplotypes responsible for a linkage signal

2007 ◽  
Vol 31 (7) ◽  
pp. 727-740 ◽  
Author(s):  
Joanna M. Biernacka ◽  
Heather J. Cordell
Keyword(s):  
Linkage Signal

scholarly journals Identification of polymorphisms explaining a linkage signal: application to the GAW14 simulated data

BMC Genetics ◽  
2005 ◽  
Vol 6 (Suppl 1) ◽  
pp. S88 ◽  
Author(s):  
Ming-Huei Chen ◽  
Paul Van Eerdewegh ◽  
Josée Dupuis
Keyword(s):  
Simulated Data ◽  
Linkage Signal

Linkage analysis demonstrates that the prothrombin G20210A mutation jointly influences plasma prothrombin levels and risk of thrombosis

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2780-2785 ◽  
Author(s):  
José Manuel Soria ◽  
Laura Almasy ◽  
Juan Carlos Souto ◽  
Isabel Tirado ◽  
Montserrat Borell ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Association Studies ◽  
Nucleotide Position ◽  
Activity Levels ◽  
Lod Score ◽  
Prothrombin Activity ◽  
Linkage Signal ◽  
G20210a Mutation ◽  
Increased Risk ◽  
Prothrombin Gene

Association studies suggest that the G20210A mutation (G to A substitution at nucleotide position 20210) in the prothrombin gene (PT) is associated with increased plasma prothrombin activity and with increased risk for venous thromboembolism. To test directly for linkage between this PT variant and plasma prothrombin activity we performed a family-based study. The G20210A genotypes and plasma prothrombin activity levels were determined in 435 individuals belonging to 22 extended Spanish families. The sample was composed of 388 homozygous (G/G) normal individuals and 43 heterozygote (G/A) and 4 homozygote (A/A) carriers for the G20210A mutation. The results of variance-component linkage analysis yielded a highly significant lod score of 3.6 (P = 2.4 × 10−5) between this mutation and a quantitative trait locus (QTL) that influences prothrombin activity. Importantly, a conditional linkage analysis that simultaneously accounted for association with the G20210A variant completely eliminated the linkage signal, which indicates that this mutation affects the function of the prothrombin gene. Additionally, a bivariate linkage analysis of plasma prothrombin activity and thrombosis significantly improved the linkage signal for prothrombin activity (lod score = 4.7;P = 1.5 × 10−6) and provided strong evidence that this QTL has a pleiotropic effect on the risk of thrombosis (lod score = 2.43; P = .0004). These results represent the first direct genetic evidence that a QTL in thePT gene influences prothrombin activity levels and susceptibility to thrombosis and strongly support the conclusion that G20210A is a functional polymorphism.

Reply to “Normalization procedures and detection of linkage signal in genetical-genomics experiments”

2006 ◽  
Vol 38 (8) ◽  
pp. 858-859 ◽  
Author(s):  
Enrico Petretto ◽  
Jonathan Mangion ◽  
Stuart A Cook ◽  
Timothy J Aitman ◽  
Michal Pravenec ◽  
...  
Keyword(s):  
Genetical Genomics ◽  
Linkage Signal

scholarly journals Assessing Whether an Allele Can Account in Part for a Linkage Signal: The Genotype-IBD Sharing Test (GIST)

2004 ◽  
Vol 74 (3) ◽  
pp. 418-431 ◽  
Author(s):  
Chun Li ◽  
Laura J. Scott ◽  
Michael Boehnke
Keyword(s):  
Linkage Signal

Reply to “Normalization procedures and detection of linkage signal in genetical-genomics experiments”

2006 ◽  
Vol 38 (8) ◽  
pp. 856-858 ◽  
Author(s):  
Elissa J Chesler ◽  
Leonid Bystrykh ◽  
Gerald de Haan ◽  
Michael P Cooke ◽  
Andrew Su ◽  
...  
Keyword(s):  
Genetical Genomics ◽  
Linkage Signal

Additional, physically ordered markers increase linkage signal for bipolar disorder on chromosome 18q22

2003 ◽  
Vol 53 (3) ◽  
pp. 239-243 ◽  
Author(s):  
Thomas G Schulze ◽  
Y.u-Sheng Chen ◽  
Judith A Badner ◽  
Melvin G McInnis ◽  
J.Raymond DePaulo ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Linkage Signal

scholarly journals A linkage and exome study of multiplex families with bipolar disorder implicates rare coding variants of ANK3 and additional rare alleles at 10q11-q21

2021 ◽  
Vol 46 (2) ◽  
Author(s):  
Claudio Toma ◽  
Alex D. Shaw ◽  
Anna Heath ◽  
Kerrie D. Pierce ◽  
Philip B. Mitchell ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Linkage Analysis ◽  
Rare Variants ◽  
Linkage Signal ◽  
Risk Variants ◽  
Genome Wide ◽  
Whole Exome ◽  
Family Based ◽  
Coding Variants ◽  
Linkage Interval

Background: Bipolar disorder is a highly heritable psychiatric condition for which specific genetic factors remain largely unknown. In the present study, we used combined whole-exome sequencing and linkage analysis to identify risk loci and dissect the contribution of common and rare variants in families with a high density of illness. Methods: Overall, 117 participants from 15 Australian extended families with bipolar disorder (72 with affective disorder, including 50 with bipolar disorder type I or II, 13 with schizoaffective disorder–manic type and 9 with recurrent unipolar disorder) underwent whole-exome sequencing. We performed genome-wide linkage analysis using MERLIN and conditional linkage analysis using LAMP. We assessed the contribution of potentially functional rare variants using a genebased segregation test. Results: We identified a significant linkage peak on chromosome 10q11-q21 (maximal single nucleotide polymorphism = rs10761725; exponential logarithm of the odds [LODexp] = 3.03; empirical p = 0.046). The linkage interval spanned 36 protein-coding genes, including a gene associated with bipolar disorder, ankyrin 3 (ANK3). Conditional linkage analysis showed that common ANK3 risk variants previously identified in genome-wide association studies — or variants in linkage disequilibrium with those variants — did not explain the linkage signal (rs10994397 LOD = 0.63; rs9804190 LOD = 0.04). A family-based segregation test with 34 rare variants from 14 genes under the linkage interval suggested rare variant contributions of 3 brain-expressed genes: NRBF2 (p = 0.005), PCDH15 (p = 0.002) and ANK3 (p = 0.014). Limitations: We did not examine non-coding variants, but they may explain the remaining linkage signal. Conclusion: Combining family-based linkage analysis with next-generation sequencing data is effective for identifying putative disease genes and specific risk variants in complex disorders. We identified rare missense variants in ANK3, PCDH15 and NRBF2 that could confer disease risk, providing valuable targets for functional characterization.

scholarly journals When linkage signal for autism MET candidate gene

2008 ◽  
Vol 17 (6) ◽  
pp. 699-700 ◽  
Author(s):  
Daniel B Campbell
Keyword(s):  
Candidate Gene ◽  
Linkage Signal

scholarly journals Joint Modeling of Linkage and Association: Identifying SNPs Responsible for a Linkage Signal

2005 ◽  
Vol 76 (6) ◽  
pp. 934-949 ◽  
Author(s):  
Mingyao Li ◽  
Michael Boehnke ◽  
Gonçalo R. Abecasis
Keyword(s):  
Joint Modeling ◽  
Linkage Signal
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