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- W1597961334 abstract "Many common diseases are highly polygenic, modulated by a large number genetic factors with small effects on susceptibility to disease. These small effects are difficult to map reliably in genetic association studies. To address this problem, researchers have developed methods that aggregate information over sets of related genes, such as biological pathways, to identify gene sets that are enriched for genetic variants associated with disease. However, these methods fail to answer a key question: which genes and genetic variants are associated with disease risk? We develop a method based on sparse multiple regression that simultaneously identifies enriched pathways, and prioritizes the variants within these pathways, to locate additional variants associated with disease susceptibility. A central feature of our approach is an estimate of the strength of enrichment, which yields a coherent way to prioritize variants in enriched pathways. We illustrate the benefits of our approach in a genome-wide association study of Crohn's disease with ~440,000 genetic variants genotyped for ~4700 study subjects. We obtain strong support for enrichment of IL-12, IL-23 and other cytokine signaling pathways. Furthermore, prioritizing variants in these enriched pathways yields support for additional disease-association variants, all of which have been independently reported in other case-control studies for Crohn's disease." @default.
- W1597961334 created "2016-06-24" @default.
- W1597961334 creator A5036504609 @default.
- W1597961334 creator A5061140470 @default.
- W1597961334 date "2012-08-21" @default.
- W1597961334 modified "2023-09-27" @default.
- W1597961334 title "Integrated analysis of variants and pathways in genome-wide association studies using polygenic models of disease" @default.
- W1597961334 cites W1483883706 @default.
- W1597961334 cites W1496451467 @default.
- W1597961334 cites W1516111018 @default.
- W1597961334 cites W1598899303 @default.
- W1597961334 cites W1642457845 @default.
- W1597961334 cites W1839028418 @default.
- W1597961334 cites W1963639770 @default.
- W1597961334 cites W1968801985 @default.
- W1597961334 cites W1969709265 @default.
- W1597961334 cites W1975705143 @default.
- W1597961334 cites W1978215768 @default.
- W1597961334 cites W1980725116 @default.
- W1597961334 cites W1980991473 @default.
- W1597961334 cites W1986863496 @default.
- W1597961334 cites W1991160835 @default.
- W1597961334 cites W1999974018 @default.
- W1597961334 cites W2006075238 @default.
- W1597961334 cites W2006543991 @default.
- W1597961334 cites W2007069447 @default.
- W1597961334 cites W2007733142 @default.
- W1597961334 cites W2010502047 @default.
- W1597961334 cites W2011197968 @default.
- W1597961334 cites W2013469333 @default.
- W1597961334 cites W2014347464 @default.
- W1597961334 cites W2016205873 @default.
- W1597961334 cites W2025471227 @default.
- W1597961334 cites W2028133290 @default.
- W1597961334 cites W2030784582 @default.
- W1597961334 cites W2038689886 @default.
- W1597961334 cites W2039608769 @default.
- W1597961334 cites W2039627167 @default.
- W1597961334 cites W2040676413 @default.
- W1597961334 cites W2041467022 @default.
- W1597961334 cites W2041669657 @default.
- W1597961334 cites W2042342193 @default.
- W1597961334 cites W2043262717 @default.
- W1597961334 cites W2043775908 @default.
- W1597961334 cites W2046247026 @default.
- W1597961334 cites W2046434400 @default.
- W1597961334 cites W2047031939 @default.
- W1597961334 cites W2047208232 @default.
- W1597961334 cites W2050029156 @default.
- W1597961334 cites W2051616601 @default.
- W1597961334 cites W2067673709 @default.
- W1597961334 cites W2070412833 @default.
- W1597961334 cites W2072063447 @default.
- W1597961334 cites W2074150439 @default.
- W1597961334 cites W2078803352 @default.
- W1597961334 cites W2087036932 @default.
- W1597961334 cites W2088449391 @default.
- W1597961334 cites W2091583677 @default.
- W1597961334 cites W2095741373 @default.
- W1597961334 cites W2096766502 @default.
- W1597961334 cites W2097099463 @default.
- W1597961334 cites W2097498614 @default.
- W1597961334 cites W2100443415 @default.
- W1597961334 cites W2102899487 @default.
- W1597961334 cites W2103551323 @default.
- W1597961334 cites W2105058392 @default.
- W1597961334 cites W2106779017 @default.
- W1597961334 cites W2108172198 @default.
- W1597961334 cites W2108366237 @default.
- W1597961334 cites W2109555487 @default.
- W1597961334 cites W2111534865 @default.
- W1597961334 cites W2111619115 @default.
- W1597961334 cites W2111842731 @default.
- W1597961334 cites W2112087830 @default.
- W1597961334 cites W2116135032 @default.
- W1597961334 cites W2116910732 @default.
- W1597961334 cites W2118448966 @default.
- W1597961334 cites W2120465937 @default.
- W1597961334 cites W2121921857 @default.
- W1597961334 cites W2122031852 @default.
- W1597961334 cites W2122189635 @default.
- W1597961334 cites W2122630333 @default.
- W1597961334 cites W2125905177 @default.
- W1597961334 cites W2128601422 @default.
- W1597961334 cites W2129559300 @default.
- W1597961334 cites W2134394193 @default.
- W1597961334 cites W2134783591 @default.
- W1597961334 cites W2136078375 @default.
- W1597961334 cites W2136091734 @default.
- W1597961334 cites W2141765180 @default.
- W1597961334 cites W2142260323 @default.
- W1597961334 cites W2142302575 @default.
- W1597961334 cites W2142752948 @default.
- W1597961334 cites W2143969914 @default.
- W1597961334 cites W2143992683 @default.
- W1597961334 cites W2146374090 @default.
- W1597961334 cites W2148564836 @default.
- W1597961334 cites W2151795480 @default.
- W1597961334 cites W2152748900 @default.
- W1597961334 cites W2154998360 @default.