We have been following-up association signals from our prior 100K genome-wide association study (GWAS) in Pima Indians. Follow-up has included genotyping more than 4200 SNPs in a sample of 3501 full heritage Pima Indians of which 613 SNPs were further genotyped in an independent sample of 3784 mixed heritage Native Americans. We are also comparing our best GWAS signals in Pima Indians with GWAS signals obtained in other populations (predominately Caucasian populations who have submitted their results to public databases). SNPs with the best replication for diabetes associations between the full heritage and mixed heritage samples mapped to KCNQ1 (combined sample P= 2 x 10-6, OR =1.26). Several of these SNPs were previously shown to be associated with diabetes in a GWAS of East Asians. Replication for diabetes associations in full and mixed heritage samples was also observed with SNPs in/near ACAD10 (combined sample P= 5 x 10-5, OR= 1.25). This gene has not been implicated in a GWAS for type 2 diabetes in other ethnic groups. Replication of associations between the full heritage Pima and mixed heritage samples was more common for BMI- associated SNPs as compared to diabetes-associated SNPs perhaps because of the younger age of the mixed heritage sample (median age = 22;therefore many of the non-diabetic individuals will likely develop diabetes). For example we identified common variation in the Map2K3 gene that is strongly associated with BMI in both full heritage and mixed heritage populations. We have found that a large portion of this gene has undergone a duplication but we have shown that only one copy of the gene is functional. We have additionally found variation in the A2BP1 gene that is highly associated with BMI in full heritage Pima Indians and French Caucasian adults. Follow-up studies of our GWAS also identified a variant unique to Pima Indians in the orexin receptor 2 gene that is highly associated with body weight. This gene has a known role in appetite regulation and satiety.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Nair, Anup K; Sutherland, Jeff R; Traurig, Michael et al. (2018) Functional and association analysis of an Amerindian-derived population-specific p.(Thr280Met) variant in RBPJL, a component of the PTF1 complex. Eur J Hum Genet 26:238-246
Shen, Jie; Guo, Tingwei; Wang, Tao et al. (2018) HLA-B*07, HLA-DRB1*07, HLA-DRB1*12, and HLA-C*03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults. Diabetes 67:861-871
Muller, Yunhua L; Skelton, Graham; Piaggi, Paolo et al. (2018) Identification and functional analysis of a novel G310D variant in the insulin-like growth factor 1 receptor (IGF1R) gene associated with type 2 diabetes in American Indians. Diabetes Metab Res Rev 34:e2994
Piaggi, Paolo; Masindova, Ivica; Muller, Yunhua L et al. (2017) A Genome-Wide Association Study Using a Custom Genotyping Array Identifies Variants in GPR158 Associated With Reduced Energy Expenditure in American Indians. Diabetes 66:2284-2295
Brown, Lisa A; Sofer, Tamar; Stilp, Adrienne M et al. (2017) Admixture Mapping Identifies an Amerindian Ancestry Locus Associated with Albuminuria in Hispanics in the United States. J Am Soc Nephrol 28:2211-2220
Sofer, Tamar; Baier, Leslie J; Browning, Sharon R et al. (2017) Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits. PLoS One 12:e0188400
Mercader, Josep M; Liao, Rachel G; Bell, Avery D et al. (2017) A Loss-of-Function Splice Acceptor Variant in IGF2 Is Protective for Type 2 Diabetes. Diabetes 66:2903-2914
Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang et al. (2017) Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun 8:1414
Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang et al. (2017) Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun 8:80
Schick, Ursula M; Jain, Deepti; Hodonsky, Chani J et al. (2016) Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans. Am J Hum Genet 98:229-42

Showing the most recent 10 out of 29 publications