ArticleAmerican journal of human genetics1999
Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases.
Article in American journal of human genetics, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed.
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- GBS Mapping and Analysis of Genes Conserved betweenInternational journal of molecular sciences · 2018Article
- Using Linkage Analysis to Detect Gene-Gene Interactions. 2. Improved Reliability and Extension to More-Complex Models.PloS one · 2016Article
- Linkage analyses in Caribbean Hispanic families identify novel loci associated with familial late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015Article
- Using linkage analysis to detect gene-gene interaction by stratifying family data on known disease, or disease-associated, alleles.PloS one · 2014Article
- A large-scale candidate gene analysis of mood disorders: evidence of neurotrophic tyrosine kinase receptor and opioid receptor signaling dysfunction.Psychiatric genetics · 2013Article
- TDT-HET: a new transmission disequilibrium test that incorporates locus heterogeneity into the analysis of family-based association data.BMC bioinformatics · 2012Article
- Chromosome 2p14 is linked to susceptibility to leprosy.PloS one · 2012Article
- Family-based designs for genome-wide association studies.Nature reviews. Genetics · 2011Review
- Statistical Analysis in Genetic Studies of Mental Illnesses.Statistical science : a review journal of the Institute of Mathematical Statistics · 2011Article
- Genome-wide linkage in Utah autism pedigrees.Molecular psychiatry · 2010Article
- Genome-wide linkage using the Social Responsiveness Scale in Utah autism pedigrees.Molecular autism · 2010Article
- Genome-wide linkage analyses of two repetitive behavior phenotypes in Utah pedigrees with autism spectrum disorders.Molecular autism · 2010Article
- Handling linkage disequilibrium in qualitative trait linkage analysis using dense SNPs: a two-step strategy.BMC genetics · 2009Article
- A recessive gene for primary vesicoureteral reflux maps to chromosome 12p11-q13.Journal of the American Society of Nephrology : JASN · 2009Article
- Significant linkage evidence for a predisposition gene for pelvic floor disorders on chromosome 9q21.American journal of human genetics · 2009Article
- Genome-wide linkage screen in familial Parkinson disease identifies loci on chromosomes 3 and 18.American journal of human genetics · 2009Article
- Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20.Psychiatric genetics · 2008Article
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3 authors.
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Abstract
Several methods have been proposed for linkage analysis of complex traits with unknown mode of inheritance. These methods include the LOD score maximized over disease models (MMLS) and the "nonparametric" linkage (NPL) statistic. In previous work, we evaluated the increase of type I error when maximizing over two or more genetic models, and we compared the power of MMLS to detect linkage, in a number of complex modes of inheritance, with analysis assuming the true model. In the present study, we compare MMLS and NPL directly. We simulated 100 data sets with 20 families each, using 26 generating models: (1) 4 intermediate models (penetrance of heterozygote between that of the two homozygotes); (2) 6 two-locus additive models; and (3) 16 two-locus heterogeneity models (admixture alpha = 1.0,.7,.5, and.3; alpha = 1.0 replicates simple Mendelian models). For LOD scores, we assumed dominant and recessive inheritance with 50% penetrance. We took the higher of the two maximum LOD scores and subtracted 0.3 to correct for multiple tests (MMLS-C). We compared expected maximum LOD scores and power, using MMLS-C and NPL as well as the true model. Since NPL uses only the affected family members, we also performed an affecteds-only analysis using MMLS-C. The MMLS-C was both uniformly more powerful than NPL for most cases we examined, except when linkage information was low, and close to the results for the true model under locus heterogeneity. We still found better power for the MMLS-C compared with NPL in affecteds-only analysis. The results show that use of two simple modes of inheritance at a fixed penetrance can have more power than NPL when the trait mode of inheritance is complex and when there is heterogeneity in the data set.
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