Supplementary Material for: Estrogen Receptor α Variants Affect Age at Onset of Alzheimer's Disease in a Multiethnic Female Cohort

<b><i>Background/Aims:</i></b> Few studies of gene variants that affect estrogen activity investigate their association with age at onset of Alzheimer's disease (AD) in women of different ethnicities. We examined the influence of <i>ESR1 </i>polymorphisms on age at onset of AD in a multiethnic cohort of women. <b><i>Methods:</i></b> Among 1,436 women participating in the Washington Heights Inwood Columbia Aging Project, association with age at AD onset was assessed for 41 single-nucleotide polymorphisms (SNPs) on the <i>ESR1</i> gene using Cox proportional hazard models, adjusting for presence of an <i>APOE</i> ε4 allele, years of education, and body mass index. <b><i>Results:</i></b> Six SNPs in self-identified White women were protectively associated with delayed age of AD onset in this self-identified group, including the two restriction fragment length polymorphisms <i>Pvu</i>II (rs2234693) and <i>Xba</i>I (rs9340799) (HR range = 0.420-0.483). Two separate SNPs were found to affect age of AD onset in self-identified Black women. <b><i>Conclusions:</i></b><i>ESR1</i> polymorphisms affect age of onset of AD in women, and risk alleles vary by ethnicity. These effects are possibly due to different linkage disequilibrium patterns or differences in comorbid environmental or cultural risk factors mediating the SNP effect on risk for AD.