publication . Article . 2011

Digging into the extremes: a useful approach for the analysis of rare variants with continuous traits?

Lamina, Claudia;
Open Access
  • Published: 01 Nov 2011 Journal: BMC Proceedings, volume 5 (eissn: 1753-6561, Copyright policy)
  • Publisher: Springer Science and Business Media LLC
Abstract
<p>Abstract</p> <p>The common disease/rare variant hypothesis predicts that rare variants with large effects will have a strong impact on corresponding phenotypes. Therefore it is assumed that rare functional variants are enriched in the extremes of the phenotype distribution. In this analysis of the Genetic Analysis Workshop 17 data set, my aim is to detect genes with rare variants that are associated with quantitative traits using two general approaches: analyzing the association with the complete distribution of values by means of linear regression and using statistical tests based on the tails of the distribution (bottom 10% of values versus top 10%). Three ...
Subjects
free text keywords: General Biochemistry, Genetics and Molecular Biology, General Medicine, Linear regression, Quantitative trait locus, Statistical hypothesis testing, Bioinformatics, Sample size determination, Exact test, Genetic analysis, Extreme value theory, Geography, Population, education.field_of_study, education, Medicine, R, Science, Q, Proceedings
Related Organizations
Funded by
NIH| Genetic Analysis of Common Diseases: An Evaluation
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01GM031575-22
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
18 references, page 1 of 2

Maher, B. Personal genomes: the case of the missing heritability. Nature. 2008; 456: 8-21 [OpenAIRE] [PubMed] [DOI]

Manolio, TA, Collins, FS, Cox, NJ, Goldstein, DB, Hindorff, LA, Hunter, DJ, McCarthy, MI, Ramos, EM, Cardon, LR, Chakravarti, A. Finding the missing heritability of complex diseases. Nature. 2009; 461: 747-753 [OpenAIRE] [PubMed] [DOI]

Goldstein, DB. Common genetic variation and human traits. New Engl J Med. 2009; 360: 1696-1698 [PubMed] [DOI]

Schork, NJ, Murray, SS, Frazer, KA, Topol, EJ. Common vs. rare allele hypotheses for complex diseases. Curr Opin Genet Dev. 2009; 19: 212-219 [OpenAIRE] [PubMed] [DOI]

Cohen, JC, Kiss, RS, Pertsemlidis, A, Marcel, YL, McPherson, R, Hobbs, HH. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science. 2004; 305: 869-872 [OpenAIRE] [PubMed] [DOI]

Cohen, JC, Pertsemlidis, A, Fahmi, S, Esmail, S, Vega, GL, Grundy, SM, Hobbs, HH. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc Natl Acad Sci USA. 2006; 103: 1810-1815 [OpenAIRE] [PubMed] [DOI]

Kotowski, IK, Pertsemlidis, A, Luke, A, Cooper, RS, Vega, GL, Cohen, JC, Hobbs, HH. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am J Hum Genet. 2006; 78: 410-422 [OpenAIRE] [PubMed] [DOI]

Nejentsev, S, Walker, N, Riches, D, Egholm, M, Todd, JA. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science. 2009; 324: 387-389 [OpenAIRE] [PubMed] [DOI]

Coassin, S, Schweiger, M, Kloss-Brandstätter, A, Lamina, C, Haun, M, Erhart, G, Paulweber, B, Rahman, Y, Olpin, S, Wolinski, H. Investigation and functional characterization of rare genetic variants in the adipose triglyceride lipase in a large healthy working population. PLoS Genet. 2010; 6: e1001239 [OpenAIRE] [PubMed] [DOI]

Li, Q, Zhang, H, Yu, K. Approaches for evaluating rare polymorphisms in genetic association studies. Hum Hered. 2010; 69: 219-228 [OpenAIRE] [PubMed] [DOI]

Almasy, LA, Dyer, TD, Peralta, JM, Kent, JW, Charlesworth, JC, Curran, JE, Blangero, J. Genetic Analysis Workshop 17 mini-exome simulation. BMC Proc. 2011; 5 (Suppl 9): S2 [OpenAIRE] [PubMed]

Li, B, Leal, SM. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am J Hum Genet. 2008; 83: 311-321 [OpenAIRE] [PubMed] [DOI]

Morgenthaler, S, Thilly, WG. A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: a cohort allelic sums test (CAST). Mutat Res. 2007; 615: 28-56 [OpenAIRE] [PubMed] [DOI]

Morris, AP, Zeggini, E. An evaluation of statistical approaches to rare variant analysis in genetic association studies. Genet Epidemiol. 2009; 34: 188-193 [OpenAIRE]

Madsen, BE, Browning, SR. A groupwise association test for rare mutations using a weighted sum statistic. PLoS Genet. 2009; 5: e1000384 [OpenAIRE] [PubMed] [DOI]

18 references, page 1 of 2
Related research
Abstract
<p>Abstract</p> <p>The common disease/rare variant hypothesis predicts that rare variants with large effects will have a strong impact on corresponding phenotypes. Therefore it is assumed that rare functional variants are enriched in the extremes of the phenotype distribution. In this analysis of the Genetic Analysis Workshop 17 data set, my aim is to detect genes with rare variants that are associated with quantitative traits using two general approaches: analyzing the association with the complete distribution of values by means of linear regression and using statistical tests based on the tails of the distribution (bottom 10% of values versus top 10%). Three ...
Subjects
free text keywords: General Biochemistry, Genetics and Molecular Biology, General Medicine, Linear regression, Quantitative trait locus, Statistical hypothesis testing, Bioinformatics, Sample size determination, Exact test, Genetic analysis, Extreme value theory, Geography, Population, education.field_of_study, education, Medicine, R, Science, Q, Proceedings
Related Organizations
Funded by
NIH| Genetic Analysis of Common Diseases: An Evaluation
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01GM031575-22
  • Funding stream: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
18 references, page 1 of 2

Maher, B. Personal genomes: the case of the missing heritability. Nature. 2008; 456: 8-21 [OpenAIRE] [PubMed] [DOI]

Manolio, TA, Collins, FS, Cox, NJ, Goldstein, DB, Hindorff, LA, Hunter, DJ, McCarthy, MI, Ramos, EM, Cardon, LR, Chakravarti, A. Finding the missing heritability of complex diseases. Nature. 2009; 461: 747-753 [OpenAIRE] [PubMed] [DOI]

Goldstein, DB. Common genetic variation and human traits. New Engl J Med. 2009; 360: 1696-1698 [PubMed] [DOI]

Schork, NJ, Murray, SS, Frazer, KA, Topol, EJ. Common vs. rare allele hypotheses for complex diseases. Curr Opin Genet Dev. 2009; 19: 212-219 [OpenAIRE] [PubMed] [DOI]

Cohen, JC, Kiss, RS, Pertsemlidis, A, Marcel, YL, McPherson, R, Hobbs, HH. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science. 2004; 305: 869-872 [OpenAIRE] [PubMed] [DOI]

Cohen, JC, Pertsemlidis, A, Fahmi, S, Esmail, S, Vega, GL, Grundy, SM, Hobbs, HH. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc Natl Acad Sci USA. 2006; 103: 1810-1815 [OpenAIRE] [PubMed] [DOI]

Kotowski, IK, Pertsemlidis, A, Luke, A, Cooper, RS, Vega, GL, Cohen, JC, Hobbs, HH. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am J Hum Genet. 2006; 78: 410-422 [OpenAIRE] [PubMed] [DOI]

Nejentsev, S, Walker, N, Riches, D, Egholm, M, Todd, JA. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science. 2009; 324: 387-389 [OpenAIRE] [PubMed] [DOI]

Coassin, S, Schweiger, M, Kloss-Brandstätter, A, Lamina, C, Haun, M, Erhart, G, Paulweber, B, Rahman, Y, Olpin, S, Wolinski, H. Investigation and functional characterization of rare genetic variants in the adipose triglyceride lipase in a large healthy working population. PLoS Genet. 2010; 6: e1001239 [OpenAIRE] [PubMed] [DOI]

Li, Q, Zhang, H, Yu, K. Approaches for evaluating rare polymorphisms in genetic association studies. Hum Hered. 2010; 69: 219-228 [OpenAIRE] [PubMed] [DOI]

Almasy, LA, Dyer, TD, Peralta, JM, Kent, JW, Charlesworth, JC, Curran, JE, Blangero, J. Genetic Analysis Workshop 17 mini-exome simulation. BMC Proc. 2011; 5 (Suppl 9): S2 [OpenAIRE] [PubMed]

Li, B, Leal, SM. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am J Hum Genet. 2008; 83: 311-321 [OpenAIRE] [PubMed] [DOI]

Morgenthaler, S, Thilly, WG. A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: a cohort allelic sums test (CAST). Mutat Res. 2007; 615: 28-56 [OpenAIRE] [PubMed] [DOI]

Morris, AP, Zeggini, E. An evaluation of statistical approaches to rare variant analysis in genetic association studies. Genet Epidemiol. 2009; 34: 188-193 [OpenAIRE]

Madsen, BE, Browning, SR. A groupwise association test for rare mutations using a weighted sum statistic. PLoS Genet. 2009; 5: e1000384 [OpenAIRE] [PubMed] [DOI]

18 references, page 1 of 2
Related research
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