Combined analysis of genome scans of dutch and finnish families reveals a susceptibility locus for high-density lipoprotein XXXX on chromosome 16q.

@entity5703 @entity2299 @entity301 @entity565 @entity377 @entity29 @entity412 @entity8944 @entity165
Several genomewide screens have been performed to identify novel loci predisposing to unfavorable serum lipid levels and @entity301 ( @entity301 ). We hypothesized that the accumulating data of these screens in different study populations could be combined to verify which of the identified loci truly harbor susceptibility genes. The power of this strategy has recently been demonstrated with other complex diseases, such as @entity29 and @entity565 . We assessed the largely unknown genetic background of @entity301 by investigating the most common @entity2299 predisposing to @entity301 , @entity5703 ( @entity5703 ), affecting 1%-2% of Western populations and 10%-20% of families with premature @entity301 . To be able to perform a combined data analysis, we unified the diagnostic criteria for @entity5703 and its component traits and combined the data from two genomewide scans performed in two populations, the Finns and the Dutch. As a result of our pooled data analysis, we identified three chromosomal regions, on chromosomes 2p25.1, 9p23, and 16q24.1, exceeding the statistical significance level of a LOD score >2.0. The 2p25.1 region was detected for the @entity5703 trait, and the 9p23 and 16q24.1 regions were detected for the low high-density lipoprotein @entity165 (HDL-C) trait. In addition, the previously recognized 1q21 region also obtained additional support in the other study sample, when the @entity412 trait was used. Analysis of the 16q24.1 region resulted in a statistically significant LOD score of 3.6 when the data from Finnish families with low HDL-C were included in the analysis. To search for the underlying gene in the 16q24.1 region, we investigated a novel functional and positional candidate gene, helix/forkhead transcription factor ( @entity8944 ), by sequencing and by genotyping of two single- @entity377 polymorphisms in the families.
