, and potentially women with high normal (35)(36)(37)(38)(39)(40)(41)(42)(43)(44) or low normal (<28) CGG repeats, are at risk of premature ovarian aging. The scarcity of population data on CGG repeats <45 CGG, and variation in raceethnicity, makes it difficult to determine true associations. DNA was analyzed for FMR1 CGG repeat lengths from 803 women (386 caucasians, 219 African Americans, 102 Japanese, and 96 Chinese) from the US-based Study of Women's Health Across the Nation (SWAN). Participants had 1 menses in the 3 months before enrollment, 1 pregnancy, no history of infertility or hormonal therapy, and menopause 46 years. Statistical analyses used Fisher exact tests. Among these women with normal reproductive histories, significant FMR1 repeat length differences were found across race-ethnicity for both the longer (P ¼ .0002) and the shorter (P < .0001) alleles. The trinucleotide length variance was greater for non-Asian than Asian women (P < .0001), despite identical median values. Our data indicate that short allele lengths <25 CGG on one or both alleles are more common in non-Asian than Asian women. We confirm the minor allele in the 35 to 39 CGG range among Asians as reported previously. Only 2 (0.3%) premutation carriers were identified. These data demonstrate that FMR1 distributions do vary by race-ethnicity, even within the ''normal'' range. This study indicates the need to control for race-ethnicity in FMR1 ovarian aging research and provides race-ethnic population data for females separated by allele.

Objective To study whether reported, but inconsistent, associations between the FMR1 CGG repeat lengths in the intermediate, high normal, or low normal range differentiate women diagnosed with diminished ovarian reserve (DOR) from population controls, and whether associations vary by race-ethnic group. Design Case-control study. Setting Academic and private fertility clinics. Patients DOR cases (n=129; 95 Caucasians, 22 Asian, 12 other) from 5 US fertility clinics were clinically diagnosed, with regular menses and no fragile X syndrome family history. Normal fertility controls (n=803; 386 Caucasians, 219 African-Americans, 102 Japanese, 96 Chinese) from the US-based SWAN Study had ≥1 menstrual period in the 3 months pre-enrollment, ≥1 pregnancy, no history of infertility or hormonal therapy, and menopause ≥46 years. Previously, the SWAN Chinese and Japanese groups had similar FMR1 CGG repeat lengths, thus they were combined. Intervention Not applicable. Main Outcome Measure FMR1 CGG repeat lengths Results Median CGG repeats were nearly identical by case/control group. DOR cases had fewer CGG repeats in the shorter FMR1 allele than controls among Caucasians, but this was not significant among Asians. Caucasian cases had fewer CGG repeats in the shorter allele than Asian cases. No significant differences were found in the high normal/intermediate range between cases and controls, or by race/ethnic group within cases in the longer allele. Conclusions This study refutes prior reports of an association between DOR and high normal/intermediate repeats, and confirms an association between DOR and low normal repeats in Caucasians.

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