Increased support for linkage of a novel locus on chromosome 5q13 for essential hypertension in the British Genetics of Hypertension Study.
Human hypertension arises from a combination of genetic factors and lifestyle influences. With cardiovascular disease set to become the number 1 cause of death worldwide, it is important to understand the etiologic mechanisms for hypertension, because these might provide new routes to improved treatment. The British Genetics of Hypertension Study has recently published a primary genome screen that identified 4 chromosomal regions of interest. We have now genotyped additional markers to confirm the most promising regions for follow-up studies. Thirty-four additional microsatellites were genotyped in our severely hypertensive affected sibling pair resource (now 1635 families with 2142 affected sibling pairs), leading to a substantial increase in information content in the regions of interest. We found increased support for linkage of chromosome 5q13 to human hypertension (multipoint logarithm of odds=2.50) with 3 adjacent markers yielding single point logarithm of odds scores of 3.22, 2.84, and 2.51. The placement of additional markers on 2q, 6q, and 9q diminished support for linkage in these regions. However, the addition of new data and families identified novel regions of interest on chromosomes 1q and 11q. The 3 positive markers in the chromosome 5 region were also genotyped in 712 distinct parent-offspring trios with the same severe phenotype to replicate linkage and association. Borderline support for replication was found (P=0.07). We found increased evidence for linkage and borderline-significant evidence for association for a hypertension susceptibility locus on chromosome 5q13 that is worthy of detailed fine mapping and assessment of candidate genes.
Munroe
Patricia B
PB
Clinical Pharmacology and Barts and the London Genome Centre, William Harvey Research Institute Barts and the London School of Medicine, Charterhouse Square, London, United Kingdom.
Wallace
Chris
C
Xue
Ming-Zhan
MZ
Marçano
Ana Carolina B
AC
Dobson
Richard J
RJ
Onipinla
Abiodun K
AK
Burke
Beverley
B
Gungadoo
Johannie
J
Newhouse
Stephen J
SJ
Pembroke
Janine
J
Brown
Morris
M
Dominiczak
Anna F
AF
Samani
Nilesh J
NJ
Lathrop
Mark
M
Connell
John
J
Webster
John
J
Clayton
David
D
Farrall
Martin
M
Mein
Charles A
CA
Caulfield
Mark
M
D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D015810:Linkage Disequilibrium; D008126:Lod Score; D018895:Microsatellite Repeats; D035781:Siblings; D006113:United Kingdom