Portrait of the family of David Stern and Bernice Stern nee Propper.

Seated: David Stern, Bernice Stern, and Jessica Agosti; left to right: Doreen Stern, her husband Michael Stern, Carol Richardson, her husband Blake Richardson, John Agosti. The baby is Katherine Stern

Studio portrait of the Amram family; Buffalo, New York.

The Amrams are related to Hans Krakauer's maternal family the Mayer/Heumann's from Billigheim and Hoffenheim

Family portrait taken in a garden on the 75th birthday of Henriette Gottschalk nee Rothschild.

Front row, from left to right: Fritz Gottschalk, Walter Gottschalk, Kurt Gottschalk, Ursula Gottschalk, Hans Ludwig (Hal) Gottschalk, Rudolf Gottschalk, Elizabeth Gottschalk; babies, from left to right: Ilse Gottschalk, Freddy Gottschalk; adults, from left to right: Karl Gottschalk, Elisabeth Gottschalk nee Steinfeld, Ernst Gottschalk, Henriette Gottschalk nee Rothschild, Therese Gottschalk nee Molling, Fritz Joseph Gottschalk

Family portrait of the Gottschalk family; Hannover, Germany.

Front Row (l-r): Frau Steinfeld (mother of Elizabeth Gottschalk nee Steinfeld and Hela Steinfeld), Fritz Gottschalk, Karl Gottschalk, Henrietta Gottschalk nee Rothschild (mother of Fritz, Karl, Anna and Ernst), Anna Catsenstein nee Gottschalk (twin of Karl Gottschalk), and Elizabeth Gottschalk; Back Row (l-r): Hela Steinfeld (sister of Elizabeth Gottschalk nee Steinfeld), Therese Gottschalk nee Molling (wife of Fritz), Leo Catsenstein (husband of Anna), Elizabeth Gottschalk nee Steinfeld (wife of Karl), Ernst Gottschalk, and Henny Molling nee Meyerhof (mother of Therese Gottschalk nee Molling)

Fritz Gottschalk's family in front of the hotel Kurhaus Brunig, Norderney; Germany.

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The Gottschalk family on the beach; Norderney, Germany.

(l-r) Elizabeth, Hans Ludwing (Hal), the maid, Ursula, Walter, Freddy, Therese (in Strandkorg) and Kurt standing

Fritz Gottschalk family with other children on the beach; Norderney, Germany.

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Emanuel Lasker and Ed Lasker playing chess Portraits Family

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Reiss family portrait; (l-r) Olga, Herbert, Flora Lotte, Walter, Moritz and Kurt; Saaz, Czechoslovakia Portraits Family

Olga Reiss nee Kohn died 1950s; Herbert Reiss, 1905-circa 1980; Flora Lotte "Lola" Reiss, 1910-1995; Walter Reiss, 1908-1937; Moritz Reiss, 1876-1965; Kurt Reiss, 1906-1996

Flora Lotte "Lola" Reiss walking in the street with her father Moritz; Karlovy Vary (Carlsbad) Portraits Family

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Flora Lotte "Lola" Reiss walking in the street with her non-Jewish boyfriend Walter; Karlovy Vary (Carlsbad) Portraits Family

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Reiss family on skiing trip; Arosa Portraits Family

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Reiss family portrait on the occasion of the wedding of Harry Gould to Eva Fantl; Royal Connaught Hotel, Hamilton, Ontario.

Standing l-r: George? son of Max Reiss?, Max Reiss, Harry Gould, Moritz Reiss, Joe Reiss, and Herbert Reiss; Seated l-r: Trude Reiss (wife of Herbert), Else Reiss (mother of Joe), Lily Friedlander Gould, Eva Fantl Gould, Trude Reiss (wife of Joe), and Marta Reiss (wife of Max)

Association between endometriosis and the interleukin 1A (IL1A) locus

STUDY QUESTION Are single-nucleotide polymorphisms (SNPs) at the interleukin 1A (IL1A) gene locus associated with endometriosis risk? SUMMARY ANSWER We found evidence for strong association between IL1A SNPs and endometriosis risk. WHAT IS KNOWN ALREADY Genetic factors contribute substantially to the complex aetiology of endometriosis and the disease has an estimated heritability of ∼51%. We, and others, have conducted genome-wide association (GWA) studies for endometriosis, which identified a total of nine independent risk loci. Recently, two small Japanese studies reported eight SNPs (rs6542095, rs11677416, rs3783550, rs3783525, rs3783553, rs2856836, rs1304037 and rs17561) at the IL1A gene locus as suggestively associated with endometriosis risk. There is also evidence of a link between inflammation and endometriosis. STUDY DESIGN, SIZE, DURATION We sought to further investigate the eight IL1A SNPs for association with endometriosis using an independent sample of 3908 endometriosis cases and 8568 controls of European and Japanese ancestry. The study was conducted between October 2013 and July 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS By leveraging GWA data from our previous multi-ethnic GWA meta-analysis for endometriosis, we imputed variants in the IL1A region, using a recent 1000 Genomes reference panel. After combining summary statistics for the eight SNPs from our European and Japanese imputed data with the published results, a fixed-effect meta-analysis was performed. An additional meta-analysis restricted to endometriosis cases with moderate-to-severe (revised American Fertility Society stage 3 or 4) disease versus controls was also performed. MAIN RESULTS AND THE ROLE OF CHANCE All eight IL1A SNPs successfully replicated at P < 0.014 in the European imputed data with concordant direction and similar size to the effects reported in the original Japanese studies. Of these, three SNPs (rs6542095, rs3783550 and rs3783525) also showed association with endometriosis at a nominal P < 0.05 in our independent Japanese sample. Fixed-effect meta-analysis of the eight SNPs for moderate-to-severe endometriosis produced a genome-wide significant association for rs6542095 (odds ratio = 1.21; 95% confidence interval = 1.13–1.29; P = 3.43 × 10−8). LIMITATIONS, REASONS FOR CAUTION The meta-analysis for moderate-to-severe endometriosis included results of moderate-to-severe endometriosis cases from our European data sets and all endometriosis cases from the Japanese data sets, as disease stage information was not available for endometriosis cases in the Japanese data sets. WIDER IMPLICATIONS OF THE FINDINGS SNP rs6542095 is located ∼2.3 kb downstream of the IL1A gene and ∼6.9 kb upstream of cytoskeleton-associated protein 2-like (CKAP2L) gene. The IL1A gene encodes the IL1a protein, a member of the interleukin 1 cytokine family which is involved in various immune responses and inflammatory processes. These results provide important replication in an independent Japanese sample and, for the first time, association of the IL1A locus in endometriosis patients of European ancestry. SNPs within the IL1A locus may regulate other genes, but if IL1A is the target, our results provide supporting evidence for a link between inflammatory responses and the pathogenesis of endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.

Kohnberger family portrait.

From left to right, back row: Ernst Schueller, Hermine Schueller, Laura Stiassny, Sigmund Stiassny, Martha Pollak, Johanna Mislap and Jacob Hermann; front row: Melanie Herrmann (or Irene Tiring), Conrad Tiring, Emilie Kohnberger and Solomon Kohnberger