Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

Yambazi Banda, Mark N Kvale, Thomas J Hoffmann, Stephanie E Hesselson, Dilrini Ranatunga, Hua Tang, Chiara Sabatti, Lisa A Croen, Brad P Dispensa, Mary Henderson, Carlos Iribarren, Eric Jorgenson, Lawrence H Kushi, Dana Ludwig, Diane Olberg, Charles P Quesenberry, Sarah Rowell, Marianne Sadler, Lori C Sakoda, Stanley Sciortino, Ling Shen, David Smethurst, Carol P Somkin, Stephen K Van Den Eeden, Lawrence Walter, Rachel A Whitmer, Pui-Yan Kwok, Catherine Schaefer, Neil Risch

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into 7 major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. PC and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed considering only non-adjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian-European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3,741 genetically-identified parent-child pairs, 93% were concordant for self-reported race/ethnicity; among 2,018 genetically-identified full-sib pairs, 96% were concordant; the lower rate for parent-child pairs was largely due to inter-marriage. The parent-child pairs revealed a trend towards increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories, creates interesting challenges and future opportunities for genetic epidemiologic studies.