Abstract 437: Reproductive Timing Related Genetic Variants from GWAS are Associated with Blood Pressure in Healthy Adolescents
Blood pressure (BP) increases in an accelerated fashion during puberty. Previous studies have identified genetic variants that were associated with the timing of reproductive aging, namely menarche and menopause. But the effects of these genetic variations on BP have not been investigated. We examined the BP effects of 46 SNPs identified in genome-wide association studies (GWAS) that were linked to age of menarche or of menopause in women of European ancestry. The current analysis was based on longitudinal data collected from 601 adolescents (338 whites and 263 blacks). Subjects were enrolled between ages 4 and 17 and followed for an average of 6 years. After adjusting for multiple testing, we found 3 of the 16 menarche-related SNPs, rs10423674 in CRTC1, rs13187289 near PHF15 and rs9635759 near CA10, were associated with a more rapid increase of BP in black males (all P< 0.0023); and two SNPs (rs17268785 in CCDC85A and rs7642134 near VGLL3) and one SNP (rs1079866 near INHBA) were associated with increased BP in black and white females, respectively (all P<0.0026). Of the 8 menarche and weight-related SNPs, rs7647305 near ETV5 was associated with increased BP in whites (P=0.0028); and 3 of the 7 menarche and height-related NPs, rs10946808 near HIST1H1D, rs6440003 in ZBTB38 and rs757608 near TBX2, were positively associated with BP in white males, white females, and black males, respectively (all P<0.005). Except for one SNP, none of the 15 menopause-related SNPs were associated with BP. The one menopause-related SNP in gene SYCP2L, rs2153157, was associated with an increase of BP in whites (P= 0.0028). Most of the associations (9 of 11) were in the direction predicted by previously observed associations with menarche or menopause ages. Furthermore, these associations did not appear to be attenuated by weight and height. In conclusion, genetic variants from previous GWAS that were associated with a women’s reproductive aging showed significant associations with BP in healthy male and female adolescents. The genetic effects were independent of a subject’s sex, race or growth related factors such as weight, height, and BMI, and thus may represent novel candidates for BP genes.
- © 2012 by American Heart Association, Inc.