Gravidity and parity in postmenopausal American Indian women: The strong heart study

The fertility of a large sample of American Indian women participating in the Strong Heart Study was examined to determine which factors are associated with variation in completed fertility among women in this population. The Strong Heart Study (SHS) is a study of cardiovascular disease (CVD) and its risk factors in American Indians living in Arizona, Oklahoma, and the Dakotas. Data were derived from a baseline examination between 1989 and 1992 of approximately 1,500 men and women, aged 45-74, from each of the 3 SHS centers. A personal interview elicited demographic information, family health history, and information on several life-style variables. A total of 1,955 ever-married, postmenopausal women were considered in these analyses. Women were considered to be postmenopausal if their menstrual cycles had stopped completely for at least 12 months, either because of natural or surgical processes. The average number of pregnancies (gravidity) for all women was 5.9, whereas the mean number of live births (parity) was 5.3. Women living in Arizona (5.6) and the Dakotas (5.8) had higher parity than those in Oklahoma (4.6). Furthermore, there was lower completed fertility in younger women: When American Indian women from all 3 centers were considered together, women born between 1910 and 1919 had a mean parity of 5.3, whereas women born between 1940 and 1949 had a mean parity of 4.0. Although previous research has suggested a relationship between parity and CVD risk factors, no linear associations between CVD risk factors and fertility were indicated in this population. We also examined the relationship of contraception, level of education, and income to fertility. While no significant relationship between contraception and the level of fertility was identified, there was a significant inverse linear relationship of both education and income with fertility. In summary, fertility rates in American Indian women are high, but appear to be decreasing in younger generations. Fertility is higher in those with less education and lower incomes

Fine mapping and identification of serum urate loci in American Indians: The Strong Heart Family Study

While studies have reported genetic loci affecting serum urate (SU) concentrations, few studies have been conducted in minority populations. Our objective for this study was to identify genetic loci regulating SU in a multigenerational family-based cohort of American Indians, the Strong Heart Family Study (SHFS). We genotyped 162,718 single nucleotide polymorphisms (SNPs) in 2000 SHFS participants using an Illumina MetaboChip array. A genome-wide association analysis of SU was conducted using measured genotype analysis approach accounting for kinships in SOLAR, and meta-analysis in METAL. Our results showed strong association of SU with rs4481233, rs9998811, rs7696092 and rs13145758 (minor allele frequency (MAF) = 25–44%; P < 3 × 10−14) of solute carrier family 2, member 9 (SLC2A9) and rs41481455, rs2231142 and rs1481012 (MAF = 29%; p < 3 × 10−9) of ATP-binding cassette protein, subfamily G, member 2 (ABCG2). Carriers of G alleles of rs9998811, rs4148155 and rs1481012 and A alleles of rs4481233, rs7696092 and rs13145758 and rs2231142 had lower SU concentrations as compared to non-carriers. Genetic analysis of SU conditional on significant SLC2A9 and ABCG2 SNPs revealed new loci, nucleobindin 1 (NUCB1) and neuronal PAS domain protein 4 (NPAS4) (p <6× 10−6). To identify American Indian-specific SNPs, we conducted targeted sequencing of key regions of SLC2A9. A total of 233 SNPs were identified of which 89 were strongly associated with SU (p < 7.1 × 10−10) and 117 were American Indian specific. Analysis of key SNPs in cohorts of Mexican-mestizos, European, Indian and East Asian ancestries showed replication of common SNPs, including our lead SNPs. Our results demonstrate the association of SU with uric acid transporters in a minority population of American Indians and potential novel associations of SU with neuronal-related genes which warrant further investigation

Use of stochastic simulations to investigate the power and design of a whole genome association study using single nucleotide polymorphism arrays in farm animals*

This paper presents a quick, easy to implement and versatile way of using stochastic simulations to investigate the power and design of using single nucleotide polymorphism (SNP) arrays for genome-wide association studies in farm animals. It illustrates the methodology by discussing a small example where 6 experimental designs are considered to analyse the same resource consisting of 6 006 animals with pedigree and phenotypic records: (1) genotyping the 30 most widely used sires in the population and all of their progeny (515 animals in total), (2) genotyping the 100 most widely used sires in the population and all of their progeny (1 102 animals in total), genotyping respectively (3) 515 and (4) 1 102 animals selected randomly or genotyping respectively (5) 515 and (6) 1 102 animals from the tails of the phenotypic distribution. Given the resource at hand, designs where the extreme animals are genotyped perform the best, followed by designs selecting animals at random. Designs where sires and their progeny are genotyped perform the worst, as even genotyping the 100 most widely used sires and their progeny is not as powerful of genotyping 515 extreme animals