New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

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

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FTO genotype is associated with phenotypic variability of body mass index

There is evidence across several species for genetic control of phenotypic variation of complex traits1, 2, 3, 4, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ~170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5, 6, 7, is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ~0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation9, 10. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

John Ettinger Collection 1941-1946

John Ettinger, 1987.

John and Ursula Schlosstein nee Gottschalk with their infant son Ralph. portraits family

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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Portrait of Alexander Moissi in costume Portraits Men

Illegible handwriting bottom right

Nineteenth century narratives reveal historic catch rates for Australian snapper (Pagrus auratus)

Snapper (Pagrus auratus) is widely distributed throughout subtropical and temperate southern oceans and forms a significant recreational and commercial fishery in Queensland, Australia. Using data from government reports, media sources, popular publications and a government fisheries survey carried out in 1910, we compiled information on individual snapper fishing trips that took place prior to the commencement of fisherywide organized data collection, from 1871 to 1939. In addition to extracting all available quantitative data, we translated qualitative information into bounded estimates and used multiple imputation to handle missing values, forming 287 records for which catch rate (snapper fisher−1 h−1) could be derived. Uncertainty was handled through a parametric maximum likelihood framework (a transformed trivariate Gaussian), which facilitated statistical comparisons between data sources. No statistically significant differences in catch rates were found among media sources and the government fisheries survey. Catch rates remained stable throughout the time series, averaging 3.75 snapper fisher−1 h−1 (95% confidence interval, 3.42–4.09) as the fishery expanded into new grounds. In comparison, a contemporary (1993–2002) south-east Queensland charter fishery produced an average catch rate of 0.4 snapper fisher−1 h−1 (95% confidence interval, 0.31–0.58). These data illustrate the productivity of a fishery during its earliest years of development and represent the earliest catch rate data globally for this species. By adopting a formalized approach to address issues common to many historical records – missing data, a lack of quantitative information and reporting bias – our analysis demonstrates the potential for historical narratives to contribute to contemporary fisheries management.

Julius Bisno collection, undated, 1780, 1801-1980.

Jewish organization executive. Primarily autographs, photos, writings, speeches, and biographical material, collected by Bisno, relating to ca. 120 Jews who have attained prominence in American public life; together with papers (1923-32) from Congregation Talmud Torah of Los Angeles, letters (1928-37) relating to other Jewish organizations in Los Angeles, and 3 letters of Stephen S. Wise, dealing with the general Jewish situation in Europe in 1933 and with the question of Jewish participation in the 1936 Olympic games. Persons represented include Benjamin N. Cardozo, Abe Fortas, Felix Frankfurter, Henry Horner, Herbert H. Lehman, and Lewis L. Strauss.

Dewey Stone papers, 1916-1983.

Contains papers and photos including correspondence and other materials relating to work as Chairman of the Jewish Agency for Palestine (and Israel), as National Chairman of the United Jewish Appeal, as a leading campaigner for Israel Bonds, and as co-founder of and Chairman of the Board of the Weizmann Institute of Science; 2 texts of radio broadcasts made in 1948 informing America about the Israeli war for independence and the new Israeli republic; a list of military equipment supplied by Mr. Stone to Israel in 1948; letters and biographical material relating both to pressure applied by Mr. Stone and others on Pres. Truman to recognize and support the new Jewish state and to Mr. Stone's financial support of Truman's campaign and the Democratic Party in 1948; materials on associations with Boston University (including the dedication of the Dewey D. and Harry K. Stone Science Building), and the Truman Library; tributes and awards; biographical material; memorials; misc. speeches, presentations, and essays; misc. press clippings; and various photographs. Among the correspondents are: Chaim Weizmann, Vera Weizmann, Abba Eban, David Ben Gurion, Harry S. Truman, John F. Kennedy, Lyndon Johnson, Richard Nixon, the Rothschilds, Hubert Humphrey, Adlai E. Stevenson II, Teddy Kollek, Golda Meir, Richard Cardinal Cushing, Jacob Fine, Henry Ford II, Solomon Goldman, John M. McCormack, Meyer Weisgal, and Stephen S. Wise.

Judah P. Benjamin collection, undated, 1838-1942.

The collection consists of 25 letters written by Benjamin between 1838 and 1881 on a variety of subjects, four Confederate notes and two bonds bearing his picture, miscellaneous items about Benjamin (1893-1942), nine issues of the Congressional globe with speeches by Benjamin, as well as separate copies of his printed speeches, and a photostatic copy of the "Diary of Events" (400 pp.) kept by Benjamin, the original of which is in the Library of Congress (1862-1864).

Franks family papers, 1711-1821, [1965-1968].

Contains business correspondence, accounts and documents relating to Jacob Franks of New York, his two sons, Moses and David, a nephew, Isaac, and a John Franks of Halifax, possibly a member of the family.