The Future of Path Analysis, Segregation Analysis, and Combined Models for Genetic Dissection of Complex Traits

Rao, D. C.; Province, Michael A.

doi:10.1159/000022889

Cited by 56 publications

(49 citation statements)

References 22 publications

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“…The Lander-Kruglyak 20 criterion (lod 43.3) has been described as being too conservative. In contrast, an lod 41.75 (Po0.0023) 21 would be equivalent to 1 false-positive region for each genome scan given a set marker density. Others suggest lod 41.18 (Po0.01) as one that should encourage further investigation.…”

Section: Methodsmentioning

confidence: 98%

Genome scan for loci linked to mite sensitivity: the Collaborative Study on the Genetics of Asthma (CSGA)

Ober²,

Beaty

et al. 2004

Genes Immun

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Section: Methodsmentioning

confidence: 98%

Genome scan for loci linked to mite sensitivity: the Collaborative Study on the Genetics of Asthma (CSGA)

Ober²,

Beaty

et al. 2004

Genes Immun

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“…We regard logarithm of the odds (LOD) scores of about 1.75 (PϽ0.0023) as promising, which represents one false positive per scan for experiments involving approximately 400 markers. 6 Linkage analysis was conducted separately in each of the black and white families.…”

Section: Linkage Analysismentioning

confidence: 99%

“…Therefore, more liberal criteria for claiming linkage than recommended by Lander and Kruglyak 5 are often adopted but with a greater reliance on replication across studies to confirm true positive signals that warrant more detailed study. 6 Several recent genomewide scans for BP or hypertension have been published. [7][8][9][10][11][12] Regions that replicate across these studies provide a fertile ground for further work to identify novel hypertension genes.…”

mentioning

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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“…The LOD score is [ 2 /(2 ϫ loge10)]. The alpha level used here to identify promising results (P Ͻ 0.0023, corresponding to a LOD score of 1.75) represents, on average, one false-positive per scan for experiments involving ϳ400 markers (24).…”

Section: Subjectsmentioning

confidence: 99%

Genome-wide linkage scan for exercise stroke volume and cardiac output in the HERITAGE Family Study

Rankinen

Pérusse

et al. 2002

Physiological Genomics

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. Genome-wide linkage scan for exercise stroke volume and cardiac output in the HERITAGE Family Study. Physiol Genomics 10: 57-62, 2002. First published June 5, 2002 10.1152/physiolgenomics.00043.2002A genome-wide linkage scan was performed for genes affecting submaximal exercise cardiac output (Q) and stroke volume (SV) in the sedentary state and their responses to a standardized 20-wk endurance training program. A total of 509 polymorphic markers were used, and 328 pairs of siblings from 99 white nuclear families and 102 sibling pairs from 105 black family units were available. Q and SV were measured in relative steady state during exercise at 50 W (Q50 and SV50, respectively). Baseline phenotypes were adjusted for age, sex, and body surface area (BSA), and the training responses (post-training Ϫ baseline, ⌬) were adjusted for age, sex, baseline BSA, and baseline value of the phenotype. Three analytical strategies were used: a multipoint variance components linkage analysis using all the family data, and regression-based single-and multipoint linkage analyses using pairs of siblings. In whites, baseline SV50 and ⌬SV50 showed promising linkages (P Ͻ 0.0023) with markers on chromosomes 14q31.1 and 10p11.2, respectively. Suggestive evidence of linkage (0.01 Ͼ P Ͼ 0.0023) for ⌬SV50 and ⌬Q50 was detected on chromosome 2q31.1 and for baseline SV50 and Q50 on chromosome 9q32-q33. In blacks, markers on 18q11.2 showed promising linkages with baseline Q50. Suggestive evidence of linkage was found in three regions for baseline SV50 (1p21.3, 3q13.3, 12q13.2) and one for baseline SV50 and Q50 (10p14). All these chromosomal regions include several potential candidate genes and therefore warrant further studies in the HERITAGE cohort and other studies. genomic scan; exercise training; linkage analysis THE COMPLETION of the Human Genome Project holds great promise for the development of new insights into biological mechanisms contributing to interindividual differences in responsiveness to acute exercise and exercise training. It has been reported that genetic factors account for a significant proportion of variability in exercise-related phenotypes, such as maximal oxygen uptake (VO 2 max ) and exercise blood pressure, both in the sedentary state and in response to endurance training (2, 4-6). Identification of the genes and mutations responsible for these genetic effects would lead to a better understanding of the biology of adaptation to exercise and, ultimately, enable individualized prescription of exercise training for performance enhancement and for prevention and treatment of several public health problems.Exercise-related phenotypes are typically multifactorial, i.e., they are affected by both environmental and genetic factors. The genetic effect is usually polygenic, i.e., it is determined by a combination of several individual genes, each having a small to moderate effect. Moreover, potential gene-gene and gene-environment interactions further complicate the dissection of the phenotypic variance. Genome-wide linkag...

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The Future of Path Analysis, Segregation Analysis, and Combined Models for Genetic Dissection of Complex Traits

Cited by 56 publications

References 22 publications

Genome scan for loci linked to mite sensitivity: the Collaborative Study on the Genetics of Asthma (CSGA)

Genome scan for loci linked to mite sensitivity: the Collaborative Study on the Genetics of Asthma (CSGA)

Genomewide Linkage Scan of Resting Blood Pressure

Genome-wide linkage scan for exercise stroke volume and cardiac output in the HERITAGE Family Study

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