Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib Pairs
Genome-wide scans performed in affected sib pairs have revealed small and often inconsistent clues to the loci responsible for the inherited components of hypertension. Since blood pressure is a quantitative trait regulated by many loci, two siblings at opposite extremes of the blood pressure distri...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/10/1862 |
| _version_ | 1797626734805254144 |
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| author | Yasmin Kevin M. O’Shaughnessy |
| author_facet | Yasmin Kevin M. O’Shaughnessy |
| author_sort | Yasmin |
| collection | DOAJ |
| description | Genome-wide scans performed in affected sib pairs have revealed small and often inconsistent clues to the loci responsible for the inherited components of hypertension. Since blood pressure is a quantitative trait regulated by many loci, two siblings at opposite extremes of the blood pressure distribution are more likely to have inherited different alleles at any given locus. Hence, we investigated an extreme discordant sib pair strategy to analyse markers from two previous loci of interest: (1) the Gordons syndrome locus that includes the WNK4 gene and (2) the ROMK locus identified in our first genome-wide scan. For this study, 24 sib pairs with strong family histories of essential hypertension were selected from the top and bottom 10% of the blood pressure distribution and genotyped for highly polymorphic microsatellite markers on chromosomes 11 and 17. The mean age of the population was 39.8 ± 7.8 years. A significant inverse correlation was found between the squared difference in pulse pressure and the number of alleles shared by IBD between the siblings for the DS11925 marker (r = −0.44, <i>p</i> = 0.031), systolic pressure and chromosome 17 markers (D17S250: r = −0.42, <i>p</i> = 0.040; D17S799 (r = −0.51, <i>p</i> = 0.011), and this relationship persisted after correcting for age and gender. Markers on chromosome 17 (D17S250, D17S928 and D17S1301) and 11 (D11S1999) also correlated with diastolic pressure. These results illustrate the successful use of discordant sib pair analysis to detect linkage within relatively small numbers of pedigrees with hypertension. Further analysis of this cohort may be valuable in complementing findings from the large genome wide scans in affected sib pairs. |
| first_indexed | 2024-03-11T10:14:25Z |
| format | Article |
| id | doaj.art-149269f86f7a4ed5928b956eaf8117a8 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T10:14:25Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-149269f86f7a4ed5928b956eaf8117a82023-11-16T10:29:35ZengMDPI AGGenes2073-44252023-09-011410186210.3390/genes14101862Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib PairsYasmin0Kevin M. O’Shaughnessy1Experimental Medicine & Immunotherapeutics Division, Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UKExperimental Medicine & Immunotherapeutics Division, Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UKGenome-wide scans performed in affected sib pairs have revealed small and often inconsistent clues to the loci responsible for the inherited components of hypertension. Since blood pressure is a quantitative trait regulated by many loci, two siblings at opposite extremes of the blood pressure distribution are more likely to have inherited different alleles at any given locus. Hence, we investigated an extreme discordant sib pair strategy to analyse markers from two previous loci of interest: (1) the Gordons syndrome locus that includes the WNK4 gene and (2) the ROMK locus identified in our first genome-wide scan. For this study, 24 sib pairs with strong family histories of essential hypertension were selected from the top and bottom 10% of the blood pressure distribution and genotyped for highly polymorphic microsatellite markers on chromosomes 11 and 17. The mean age of the population was 39.8 ± 7.8 years. A significant inverse correlation was found between the squared difference in pulse pressure and the number of alleles shared by IBD between the siblings for the DS11925 marker (r = −0.44, <i>p</i> = 0.031), systolic pressure and chromosome 17 markers (D17S250: r = −0.42, <i>p</i> = 0.040; D17S799 (r = −0.51, <i>p</i> = 0.011), and this relationship persisted after correcting for age and gender. Markers on chromosome 17 (D17S250, D17S928 and D17S1301) and 11 (D11S1999) also correlated with diastolic pressure. These results illustrate the successful use of discordant sib pair analysis to detect linkage within relatively small numbers of pedigrees with hypertension. Further analysis of this cohort may be valuable in complementing findings from the large genome wide scans in affected sib pairs.https://www.mdpi.com/2073-4425/14/10/1862blood pressuremicrosatellite markerschromosomes 11 and 17extreme discordant sib pairs |
| spellingShingle | Yasmin Kevin M. O’Shaughnessy Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib Pairs Genes blood pressure microsatellite markers chromosomes 11 and 17 extreme discordant sib pairs |
| title | Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib Pairs |
| title_full | Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib Pairs |
| title_fullStr | Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib Pairs |
| title_full_unstemmed | Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib Pairs |
| title_short | Genetic Markers Regulating Blood Pressure in Extreme Discordant Sib Pairs |
| title_sort | genetic markers regulating blood pressure in extreme discordant sib pairs |
| topic | blood pressure microsatellite markers chromosomes 11 and 17 extreme discordant sib pairs |
| url | https://www.mdpi.com/2073-4425/14/10/1862 |
| work_keys_str_mv | AT yasmin geneticmarkersregulatingbloodpressureinextremediscordantsibpairs AT kevinmoshaughnessy geneticmarkersregulatingbloodpressureinextremediscordantsibpairs |