Tyrosine hydroxylase: another piece of the genetics of hypertension puzzle.

Investigations of the genetic underpinnings of hypertension have had a long history that includes twin studies, adoption studies, and family studies. Subsequent large pedigree studies showed substantial heritability for many traits related to hypertension.1,2 Guided by these high heritabilities, segregation analysis provided evidence that common mendelian genes had moderate to large effects on multiple intermediate phenotypes for blood pressure and for blood pressure itself.3 Subsequent linkage analyses suggested that these large common gene effects were not as strong as originally thought because few linkage signals reached the strength seen for known monogenic traits.4,5 The excitement surrounding the potential of whole-genome linkage scans seemed to diminish because few scans agreed on the same chromosome regions. However, as more scans have been published and more meta-analyses performed, increasing consensus exists for particular chromosomal regions containing genes contributing to blood pressure control (see the National Heart, Lung, and Blood Institute GENELINK metaanalysis Web site, https://genelink.nhlbi.nih.gov/index.jsp). Recently, a number of genes have been discovered by fine mapping regions under linkage peaks (SLC4A5, ATP1B1, SELE, RGS5), suggesting that despite the lack of universal agreement of multiple scans on linked regions and only moderately sized linkage statistics, it is still possible to find disease genes under linkage signals.6,7