publication . Article . 2010

Investigation and Functional Characterization of Rare Genetic Variants in the Adipose Triglyceride Lipase in a Large Healthy Working Population

simon olpin; Heimo Wolinski; Stefan Coassin; Florian Kronenberg; Robert Zimmermann; Martina Schweiger; Claudia Lamina;
Open Access English
  • Published: 01 Dec 2010 Journal: PLoS Genetics, volume 6, issue 12 (issn: 1553-7390, eissn: 1553-7404, Copyright policy)
  • Publisher: Public Library of Science
Abstract
Recent studies demonstrated a strong influence of rare genetic variants on several lipid-related traits. However, their impact on free fatty acid (FFA) plasma concentrations, as well as the role of rare variants in a general population, has not yet been thoroughly addressed. The adipose triglyceride lipase (ATGL) is encoded by the PNPLA2 gene and catalyzes the rate-limiting step of lipolysis. It represents a prominent candidate gene affecting FFA concentrations. We therefore screened the full genomic region of ATGL for mutations in 1,473 randomly selected individuals from the SAPHIR (Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk...
Subjects
free text keywords: Research Article, Genetics and Genomics/Complex Traits, Genetics and Genomics/Functional Genomics, Genetics and Genomics/Gene Function, QH426-470, Genetics(clinical), Genetics, Cancer Research, Ecology, Evolution, Behavior and Systematics, Molecular Biology
Funded by
FWF| Metabolic lipases in lipid and energy metabolism
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: Z 136
  • Funding stream: Wittgenstein-Preis
61 references, page 1 of 5

Manolio, TA, Collins, FS, Cox, NJ, Goldstein, DB, Hindorff, LA. Finding the missing heritability of complex diseases.. Nature. 2009; 461: 747-753 [OpenAIRE] [PubMed]

Reich, DE, Lander, ES. On the allelic spectrum of human disease.. Trends Genet. 2001; 17: 502-510 [PubMed]

Pritchard, JK. Are rare variants responsible for susceptibility to complex diseases?. Am J Hum Genet. 2001; 69: 124-137 [OpenAIRE] [PubMed]

Bodmer, W, Bonilla, C. Common and rare variants in multifactorial susceptibility to common diseases.. Nat Genet. 2008; 40: 695-701 [OpenAIRE] [PubMed]

Kronenberg, F. Genome-wide association studies in aging-related processes such as diabetes mellitus, atherosclerosis and cancer.. Exp Gerontol. 2008; 43: 39-43 [PubMed]

Frazer, KA, Murray, SS, Schork, NJ, Topol, EJ. Human genetic variation and its contribution to complex traits.. Nat Rev Genet. 2009; 10: 241-251 [PubMed]

Maher, B. Personal genomes: The case of the missing heritability.. Nature. 2008; 456: 18-21 [PubMed]

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

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]

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

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

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

Romeo, S, Pennacchio, LA, Fu, Y, Boerwinkle, E, Tybjaerg-Hansen, A. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL.. Nat Genet. 2007; 39: 513-516 [OpenAIRE] [PubMed]

Ahituv, N, Kavaslar, N, Schackwitz, W, Ustaszewska, A, Martin, J. Medical sequencing at the extremes of human body mass.. Am J Hum Genet. 2007; 80: 779-791 [OpenAIRE] [PubMed]

Ji, W, Foo, JN, O'Roak, BJ, Zhao, H, Larson, MG. Rare independent mutations in renal salt handling genes contribute to blood pressure variation.. Nat Genet. 2008; 40: 592-599 [OpenAIRE] [PubMed]

61 references, page 1 of 5
Abstract
Recent studies demonstrated a strong influence of rare genetic variants on several lipid-related traits. However, their impact on free fatty acid (FFA) plasma concentrations, as well as the role of rare variants in a general population, has not yet been thoroughly addressed. The adipose triglyceride lipase (ATGL) is encoded by the PNPLA2 gene and catalyzes the rate-limiting step of lipolysis. It represents a prominent candidate gene affecting FFA concentrations. We therefore screened the full genomic region of ATGL for mutations in 1,473 randomly selected individuals from the SAPHIR (Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk...
Subjects
free text keywords: Research Article, Genetics and Genomics/Complex Traits, Genetics and Genomics/Functional Genomics, Genetics and Genomics/Gene Function, QH426-470, Genetics(clinical), Genetics, Cancer Research, Ecology, Evolution, Behavior and Systematics, Molecular Biology
Funded by
FWF| Metabolic lipases in lipid and energy metabolism
Project
  • Funder: Austrian Science Fund (FWF) (FWF)
  • Project Code: Z 136
  • Funding stream: Wittgenstein-Preis
61 references, page 1 of 5

Manolio, TA, Collins, FS, Cox, NJ, Goldstein, DB, Hindorff, LA. Finding the missing heritability of complex diseases.. Nature. 2009; 461: 747-753 [OpenAIRE] [PubMed]

Reich, DE, Lander, ES. On the allelic spectrum of human disease.. Trends Genet. 2001; 17: 502-510 [PubMed]

Pritchard, JK. Are rare variants responsible for susceptibility to complex diseases?. Am J Hum Genet. 2001; 69: 124-137 [OpenAIRE] [PubMed]

Bodmer, W, Bonilla, C. Common and rare variants in multifactorial susceptibility to common diseases.. Nat Genet. 2008; 40: 695-701 [OpenAIRE] [PubMed]

Kronenberg, F. Genome-wide association studies in aging-related processes such as diabetes mellitus, atherosclerosis and cancer.. Exp Gerontol. 2008; 43: 39-43 [PubMed]

Frazer, KA, Murray, SS, Schork, NJ, Topol, EJ. Human genetic variation and its contribution to complex traits.. Nat Rev Genet. 2009; 10: 241-251 [PubMed]

Maher, B. Personal genomes: The case of the missing heritability.. Nature. 2008; 456: 18-21 [PubMed]

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

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]

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

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

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

Romeo, S, Pennacchio, LA, Fu, Y, Boerwinkle, E, Tybjaerg-Hansen, A. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL.. Nat Genet. 2007; 39: 513-516 [OpenAIRE] [PubMed]

Ahituv, N, Kavaslar, N, Schackwitz, W, Ustaszewska, A, Martin, J. Medical sequencing at the extremes of human body mass.. Am J Hum Genet. 2007; 80: 779-791 [OpenAIRE] [PubMed]

Ji, W, Foo, JN, O'Roak, BJ, Zhao, H, Larson, MG. Rare independent mutations in renal salt handling genes contribute to blood pressure variation.. Nat Genet. 2008; 40: 592-599 [OpenAIRE] [PubMed]

61 references, page 1 of 5
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