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.

Age-related changes in hepatic function: An update on implications for drug therapy

The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people’s responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of ‘start low, go slow’ should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians.

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.

Graenum Berger papers, undated, (1825)-2002

Contains correspondence, minutes, reports, clippings, manuscripts, research materials, journal articles, photographs and publications; primarily relating to Berger's involvement with Ethiopian Jewry and his efforts to bring about their rescue through the organization he formed, the American Association for Ethiopian Jews. Also contains material from Berger's other interests- his writings, travels through the world and to Israel and Ethiopia, community affiliations, research in Black American Jews, profession as a Jewish social work executive, his commitment to Jewish causes and to Israel. There are also many personal and biographical materials from the numerous long-term friendships and associations he established.

Uriah P. Levy collection undated, 1787-1948, 1959, 1961, 1985, 2005.

Contains the notebook and correspondence of Abram Kanof relating to the naval career and activities of Uriah P. Levy; the correspondence, memoranda, newspaper clippings, and a manuscript paper of Isaac Markens pertaining to the alleged claim that Levy was instrumental in abolishing flogging in the Navy; personal documents including a letter to Captain E.A.F. Lavalette concerning the behavior of officers under Levy's command as commodore of the Mediterranean fleet (1859), a photostatic copy of his will and the inventory of his estate (1862), and published material by and about Uriah Phillips Levy including a bound typewritten copy of "Record of Naval Court of Inquiry, 1857;" An essay on flogging in the Navy, 1849; Memorial of Uriah P. Levy, ... 1855; an original copy of a Manual of rules for men-of-war by Captain U.P. Levy, 1862; and Monticello and its preservation, since Jefferson's death, 1862-1902, by George Alfred Townsend. Also contains the halitza of Virginia Lopez Levy, widow of Uriah P. Levy, 1866, signed by J.J. Lyons; copies of letters of Michael Levy to Henry Deering and Dudley Woolridge, 1787-1788, and a published copy of The defense of Captain Jonas P. Levy. Gift, in part, of the Elsie O. and Philip D. Sang Foundation, 1979 and of Herman Herst, Jr., 1987.

Jules Wertheimer family collection.

Family trees listing; newspaper clippings on Nazi period in Wertheim; inscriptions from Jewish cemetery in Schmieheim.

Noah's Weekly Messenger

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New York Enquirer, vol. 1, no. 3

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Letter from Daniel I.M. Peixotto

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Descendants of Benjamin Seixas

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Photos of Gomez coat of arms and other Gomez items

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Pennsylvania Packet and Daily Advertiser. Containing anecdote regarding Oliver Cromwell and the Jew

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Seixas family registers

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Description of Beth Haim, Newport, and copy of deed

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Consecration prayer for Mill Street or Crosby Street synagogues

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