Genome-wide search for genes related to the fat-free body mass in the Québec family study

Chagnon, Yvon C.; Borecki, Ingrid B.; Pérusse, Louis; Roy, Sonia; Lacaille, Michel; Chagnon, Monique; Ho-Kim, My Anh; Rice, Treva; Province, Michael A.; Rao, D. C.; Bouchard, Claude

doi:10.1016/s0026-0495(00)91299-x

Cited by 105 publications

(64 citation statements)

References 29 publications

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“…Particularly, a positive linkage for fat-free mass with a LOD of 2.7 at marker D7S1808 (7p15.3) was detected in the Quebec Family Study data using a genome scan linkage analysis. 36 Another region (58-72 cM) with a maximum LOD score of 2.2 at 69 cM near the marker D7S1818 (7q11.1) showed a linkage to incremental AUC in this study. But no obvious candidates have been proposed in this region.…”

Section: Discussionsupporting

confidence: 51%

An autosomal genome scan for loci influencing longitudinal burden of body mass index from childhood to young adulthood in white sibships: The Bogalusa Heart Study

Chen

Cook

et al. 2004

Int J Obes

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OBJECTIVE:To examine genetic loci linked to a long-term burden and trend of obesity traits, such as body mass index (BMI), from childhood to adulthood. DESIGN: Longitudinal study using serial measurements of BMI from childhood. SUBJECTS: A total of 782 unselected white siblings (representing 521 full and 39 half sib-pairs) from 342 families enrolled in the Bogalusa Heart Study. MEASUREMENTS: A total of 357 microsatellite markers with an average spacing of 9.0 cM spanning the 22 autosomal chromosomes were typed. A quadratic growth curve was developed using a random effects model based on serial measurements of BMI from childhood to adulthood. The serial changes in BMI were measured in terms of long-term burden (area under the curve (AUC) divided by follow-up years) and the long-term trend (incremental AUC, calculated as total AUCÀbaseline AUC). RESULTS: Heritability estimates of long-term measures were 0.78 for total AUC and 0.43 for incremental AUC. In a variancecomponent-based multipoint linkage analysis with SOLAR, linkage to the long-term measures of BMI was observed on chromosomes 1, 5, 7, 12, 13 and 18. For total AUC, LOD scores were 3.0 at 110 cM on chromosome 12, 2.9 at 26 cM and 2.4 at 52 cM on chromosome 7, and 2.2 at 126 cM on chromosome 5. For incremental AUC, LOD scores were 2.9 at 26 cM, 2.1 at 97 cM and 2.3 at 110 cM on chromosome 12, 2.2 at 69 cM on chromosome 7, 2.2 at 91 cM and 2.5 at 150 cM on chromosome 1, 2.0 at 119 cM on chromosome 5, 2.0 at 54 cM on chromosome 13 and 2.0 at 7 cM on chromosome 18. Several important obesity-related candidate genes are located in the regions or near the markers showing positive linkage. CONCLUSION: Linkage evidence found in this study indicates that regions on these chromosomes might harbor genetic loci that affect the propensity to develop obesity from childhood.

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Section: Discussionsupporting

confidence: 51%

An autosomal genome scan for loci influencing longitudinal burden of body mass index from childhood to young adulthood in white sibships: The Bogalusa Heart Study

Chen

Cook

et al. 2004

Int J Obes

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“…A semiautomated genotyping procedure using laser infrared automatic DNA sequencers, and automated genotyping software (SAGA) from LICOR were used. 44 Microsatellite genotypes were called automatically using the SAGA software. After automatic genotyping, which was read blind to the phenotypes, manual editing of the results was performed when needed.…”

Section: Genotypingmentioning

confidence: 99%

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families

et al. 2004

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The goal of this study was to identify susceptibility loci shared by schizophrenia (SZ) and bipolar disorder (BP), or specific to each. To this end, we performed a dense genome scan in a first sample of 21 multigenerational families of Eastern Quebec affected by SZ, BP or both (N ¼ 480 family members). This probably constitutes the first genome scan of SZ and BP that used the same ascertainment, statistical and molecular methods for the concurrent study of the two disorders. We genotyped 607 microsatellite markers of which 350 were spaced by 10 cM and 257 others were follow-up markers in positive regions at the 10 cM scan. Lander and Kruglyak thresholds were conservatively adjusted for multiple testings. We maximized the lod scores (mod score) over eight combinations (2 phenotype severity levels Â 2 models of transmission Â 2 analyses, affected/unaffected vs affected-only). We observed five genomewide significant linkages with mod score 44.0: three for BP (15q11.1, 16p12.3, 18q12-q21) and two for the shared phenotype, that is, the common locus (CL) phenotype (15q26,18q12-q21). Nine mod scores exceeded the suggestive threshold of 2.6: three for BP (3q21, 10p13, 12q23), three for SZ (6p22, 13q13, 18q21) and three for the CL phenotype (2q12.3, 13q14, 16p13). Mod scores 41.9 might represent confirmatory linkages of formerly reported genomewide significant findings such as our finding in 6p22.3 for SZ. Several regions appeared to be shared by SZ and BP. One linkage signal (15q26) appeared novel, whereas others overlapped formerly reported susceptibility regions. Despite the methodological limitations we raised, our data support the following trends: (i) results from several genome scans of SZ and BP in different populations tend to converge in specific genomic regions and (ii) some of these susceptibility regions may be shared by SZ and BP, whereas others may be specific to each. The present results support the relevance of investigating concurrently SZ and BP within the same study and have implications for the modelling of genetic effects. Molecular Psychiatry (2005) 10, 486-499.

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“…PCR conditions, genotyping methods, and checks for Mendelian incompatibilities are outlined elsewhere 17 (see expanded Methods section in an online data supplement available at http://www. hypertensionaha.org).…”

Section: Marker Datamentioning

confidence: 99%

Genomewide Linkage Scan of Resting Blood Pressure

et al. 2002

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Abstract-The purpose of this study was to search for genomic regions influencing resting systolic (SBP) and diastolic (DBP) blood pressure (BP) in sedentary families (baseline), and for resting BP responses (changes) resulting from a 20-week exercise training intervention (post-training-baseline) in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. A genome-wide scan was conducted on 317 black individuals from 114 families and 519 white individuals from 99 families using a multipoint variance-components linkage model and a panel of 509 markers. Promising results were primarily, but not exclusively, found in the black families. Linkage evidence (PϽ0.0023) with baseline BP replicated other studies within a 1-logarithm of odds (LOD) interval on 2p14, 3p26.3, and 12q21.33, and provided new evidence on 3q28, 11q21, and 19p12. Results for several known hypertension genes were less compelling. For response BP, results were not very strong, although markers on 13q11 were mildly suggestive (PϽ0.01). In conclusion, these HERITAGE data, in conjunction with results from previous genomewide scans, provide a basis for planning future investigations. The major areas warranting further study involve fine mapping to narrow down 3 regions on 2q, 3p, and 12q that may contain "novel" hypertension genes, additional typing of some biological candidate genes to determine whether they are the sources of these and other signals, multilocus investigations to understand how and to what extent some of these candidates may interact, and multivariate studies to characterize any pleiotropy.

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Genome-wide search for genes related to the fat-free body mass in the Québec family study

Cited by 105 publications

References 29 publications

An autosomal genome scan for loci influencing longitudinal burden of body mass index from childhood to young adulthood in white sibships: The Bogalusa Heart Study

An autosomal genome scan for loci influencing longitudinal burden of body mass index from childhood to young adulthood in white sibships: The Bogalusa Heart Study

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families

Genomewide Linkage Scan of Resting Blood Pressure

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