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. 2007 Oct 1:8:66.
doi: 10.1186/1471-2156-8-66.

Homozygosity by descent mapping of blood pressure in the Old Order Amish: evidence for sex specific genetic architecture

Patrick F McArdle  1 , Harvey Dytch, Jeffery R O'Connell, Alan R Shuldiner, Braxton D Mitchell, Mark Abney
Affiliations

Homozygosity by descent mapping of blood pressure in the Old Order Amish: evidence for sex specific genetic architecture

Patrick F McArdle et al. BMC Genet. .

Abstract

Background: High blood pressure is a well established risk factor for morbidity and mortality acting through heart disease, stroke and cardiovascular disease. Genome wide scans have linked regions of nearly every human chromosome to blood pressure related traits. We have capitalized on beneficial qualities of the Old Order Amish of Lancaster, PA, a closed founder population with a relatively small number of founders, to perform a genome wide homozygosity by descent mapping scan. Each individual in the study has a non zero probability of consanguinity. Systolic and diastolic blood pressures are shown to have appreciable dominance variance components.

Results: Areas of two chromosomes were identified as suggestive of linkage to SBP and 5 areas to DBP in either the overall or sex specific analyses. The strongest evidence for linkage in the overall sample was to Chromosome 18q12 (LOD = 2.6 DBP). Sex specific analyses identified a linkage on Chromosome 4p12-14 (LOD in men only = 3.4 SBP). At Chromosome 2q32-33, an area where we previously reported significant evidence for linkage to DBP using a conventional identity by descent approach, the LOD was 1.4; however an appreciable sex effect was observed with men accounting for most of the linkage (LOD in men only = 2.6).

Conclusion: These results add evidence to a sex specific genetic architecture to blood pressure related traits, particularly in regions of linkage on chromosome 2, 4 and 18.

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Figures

Figure 1
Figure 1
Estimated LOD score obtained from HBD mapping of SBP on Chromosome 4. Linkage results are given for the overall sample and men and women separately. (sbp-med: systolic blood pressure with those on medication removed, sbpAdj = systolic blood pressure adjusted for medication as described in text).
Figure 2
Figure 2
Estimated LOD score obtained from HBD mapping of DBP on Chromosome 18. Linkage results are given for the overall sample and men and women separately. (dbp-med: diastolic blood pressure with those on medication removed, dbpAdj = diastolic blood pressure adjusted for medication as described in text).
Figure 3
Figure 3
Estimated LOD score obtained from HBD mapping of DBP on Chromosome 2. Linkage results are given for the overall sample and men and women separately. (dbp-med: diastolic blood pressure with those on medication removed, dbpAdj = diastolic blood pressure adjusted for medication as described in text).
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