Multiple Rare Alleles Contribute to Low Plasma Levels of HDL Cholesterol

by: Jonathan C Cohen, Robert S Kiss, Alexander Pertsemlidis, Yves L Marcel, Ruth Mcpherson, Helen H Hobbs

Science, Vol. 305, No. 5685. (6 August 2004), pp. 869-872.

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Abstract

Heritable variation in complex traits is generally considered to be conferred by common DNA sequence polymorphisms. We tested whether rare DNA sequence variants collectively contribute to variation in plasma levels of highdensity lipoprotein cholesterol (HDL-C). We sequenced three candidate genes (ABCA1, APOA1, and LCAT) that cause Mendelian forms of low HDL-C levels in individuals from a population-based study. Nonsynonymous sequence variants were significantly more common (16% versus 2%) in individuals with low HDL-C (<fifth percentile) than in those with high HDL-C (>95th percentile). Similar findings were obtained in an independent population, and biochemical studies indicated that most sequence variants in the low HDL-C group were functionally important. Thus, rare alleles with major phenotypic effects contribute significantly to low plasma HDL-C levels in the general population. 10.1126/science.1099870

@article{citeulike:1042351, abstract = {Heritable variation in complex traits is generally considered to be conferred by common DNA sequence polymorphisms. We tested whether rare DNA sequence variants collectively contribute to variation in plasma levels of highdensity lipoprotein cholesterol (HDL-C). We sequenced three candidate genes (ABCA1, APOA1, and LCAT) that cause Mendelian forms of low HDL-C levels in individuals from a population-based study. Nonsynonymous sequence variants were significantly more common (16\% versus 2\%) in individuals with low HDL-C (<fifth percentile) than in those with high HDL-C (>95th percentile). Similar findings were obtained in an independent population, and biochemical studies indicated that most sequence variants in the low HDL-C group were functionally important. Thus, rare alleles with major phenotypic effects contribute significantly to low plasma HDL-C levels in the general population. 10.1126/science.1099870}, author = {Cohen, Jonathan C. and Kiss, Robert S. and Pertsemlidis, Alexander and Marcel, Yves L. and Mcpherson, Ruth and Hobbs, Helen H. }, citeulike-article-id = {1042351}, doi = {10.1126/science.1099870}, journal = {Science}, keywords = {association, rare\_alleles}, month = {August}, number = {5685}, pages = {869--872}, posted-at = {2008-05-07 14:27:07}, priority = {2}, title = {Multiple Rare Alleles Contribute to Low Plasma Levels of HDL Cholesterol}, url = {http://dx.doi.org/10.1126/science.1099870}, volume = {305}, year = {2004} }

RIS record

TY - JOUR ID - citeulike:1042351 L3 - citeulike-article-id:1042351 TI - Multiple Rare Alleles Contribute to Low Plasma Levels of HDL Cholesterol JF - Science VL - 305 IS - 5685 SP - 869 EP - 872 N2 - Heritable variation in complex traits is generally considered to be conferred by common DNA sequence polymorphisms. We tested whether rare DNA sequence variants collectively contribute to variation in plasma levels of highdensity lipoprotein cholesterol (HDL-C). We sequenced three candidate genes (ABCA1, APOA1, and LCAT) that cause Mendelian forms of low HDL-C levels in individuals from a population-based study. Nonsynonymous sequence variants were significantly more common (16% versus 2%) in individuals with low HDL-C (<fifth percentile) than in those with high HDL-C (>95th percentile). Similar findings were obtained in an independent population, and biochemical studies indicated that most sequence variants in the low HDL-C group were functionally important. Thus, rare alleles with major phenotypic effects contribute significantly to low plasma HDL-C levels in the general population. 10.1126/science.1099870 KW - association KW - rare_alleles AU - Cohen, Jonathan AU - Kiss, Robert AU - Pertsemlidis, Alexander AU - Marcel, Yves AU - Mcpherson, Ruth AU - Hobbs, Helen PY - 2004/08/06/ UR - http://dx.doi.org/10.1126/science.1099870 ER -

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