Isidor Simon seated at an outdoor table with his wife Friederike nee Falkenburg and two grandchildren, Helmuth and Walther Simon Portraits Family

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Kisch family portrait; Alexander, Mizzi, Charlotte, Guido and Bruno (l-r); Prague.

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Genome-wide linkage and association analyses implicate FASN in predisposition to Uterine Leiomyomata

Uterine leiomyomata (UL), the most prevalent pelvic tumors in women of reproductive age, pose a major public health problem given their high frequency, associated morbidities, and most common indication for hysterectomies. A genetic component to UL predisposition is supported by analyses of ethnic predisposition, twin studies, and familial aggregation. A genome-wide SNP linkage panel was genotyped and analyzed in 261 white UL-affected sister-pair families from the Finding Genes for Fibroids study. Two significant linkage regions were detected in 10p11 (LOD = 4.15) and 3p21 (LOD = 3.73), and five additional linkage regions were identified with LOD scores > 2.00 in 2q37, 5p13, 11p15, 12q14, and 17q25. Genome-wide association studies were performed in two independent cohorts of white women, and a meta-analysis was conducted. One SNP (rs4247357) was identified with a p value (p = 3.05 x 10(-8)) that reached genome-wide significance (odds ratio = 1.299). The candidate SNP is under a linkage peak and in a block of linkage disequilibrium in 17q25.3, which spans fatty acid synthase (FASN), coiled-coil-domain-containing 57 (CCDC57), and solute-carrier family 16, member 3 (SLC16A3). By tissue microarray immunohistochemistry, we found elevated (3-fold) FAS levels in UL-affected tissue compared to matched myometrial tissue. FAS transcripts and/or protein levels are upregulated in various neoplasms and implicated in tumor cell survival. FASN represents the initial UL risk allele identified in white women by a genome-wide, unbiased approach and opens a path to management and potential therapeutic intervention.

Reproduction of photograph of Kaufman and Rosenberg family portrait on the occasion of the wedding of Ludwig Rosenberg and Paula Rosenberg nee Joseph (left); Hamburg.

Includes Ludwig Rosenberg and Paula Rosenberg nee Joseph (left), Thekla (Tekie) Joseph (standing center), Karl Kaufman and Else Kaufman (right)

Schoenewald family portrait; Bad Nauheim, Germany.

Includes Rosi Schoenewald (sister of Dora), Dora Schoenewald (wife of Alfred Apfel and mother of Hannah Busoni), Henni Apfel, Tilly Schoenewald, Luise Schoenewald, Max Schoenewald (brother of Dora), Felix Schoenewald (brother of Dora), Samuel Schoenewald (brother of Dora), and Gerhardt Schoenewald

Family portrait with six unidentified men and women around a dining table holding up large glasses of beer.

Handwritten caption: Es war einmal (Once upon a time there was)

Herz? family studio portrait.

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Portrait of Wladimir Eliasberg with his eldest daughter Eva Eliasberg (later Chava Hareli); Vienna Portraits Family

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Family portrait of siblings Wladimir, Rosa, Lena and Georg Eliasberg; New York Portraits Family

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Samuel Eliasberg in a park with his son Georg Eliasberg; Berlin Portraits Family

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Rieser family portrait on the steps of an unidentified building Portraits Family

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Gans family portraits on Delft platter Portraits Family

Top row: Alexander Gans and his wife